Future targets for migraine treatment beyond CGRP

Background Migraine is a disabling and chronic neurovascular headache disorder. Trigeminal vascular activation and release of calcitonin gene-related peptide (CGRP) play a pivotal role in the pathogenesis of migraine. This knowledge has led to the development of CGRP(-receptor) therapies. Yet, a substantial proportion of patients do not respond to these treatments. Therefore, alternative targets for future therapies are warranted. The current narrative review provides a comprehensive overview of the pathophysiological role of these possible non-CGRP targets in migraine. Findings We covered targets of the metabotropic receptors (pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), amylin, and adrenomedullin), intracellular targets (nitric oxide (NO), phosphodiesterase-3 (PDE3) and -5 (PDE5)), and ion channels (potassium, calcium, transient receptor potential (TRP), and acid-sensing ion channels (ASIC)). The majority of non-CGRP targets were able to induce migraine-like attacks, except for (i) calcium channels, as it is not yet possible to directly target channels to elucidate their precise involvement in migraine; (ii) TRP channels, activation of which can induce non-migraine headache; and (iii) ASICs, as their potential in inducing migraine attacks has not been investigated thus far. Drugs that target its receptors exist for PACAP, NO, and the potassium, TRP, and ASIC channels. No selective drugs exist for the other targets, however, some existing (migraine) treatments appear to indirectly antagonize responses to amylin, adrenomedullin, and calcium channels. Drugs against PACAP, NO, potassium channels, TRP channels, and only a $ PAC_{1} $ antibody have been tested for migraine treatment, albeit with ambiguous results. Conclusion While current research on these non-CGRP drug targets has not yet led to the development of efficacious therapies, human provocation studies using these targets have provided valuable insight into underlying mechanisms of migraine headaches and auras. Further studies are needed on these alternative therapies in non-responders of CGRP(-receptor) targeted therapies with the ultimate aim to pave the way towards a headache-free future for all migraine patients. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Al-Hassany, Linda [verfasserIn] Boucherie, Deirdre M. Creeney, Hannah van Drie, Ruben W. A. Farham, Fatemeh Favaretto, Silvia Gollion, Cédric Grangeon, Lou Lyons, Hannah Marschollek, Karol Onan, Dilara Pensato, Umberto Stanyer, Emily Waliszewska-Prosół, Marta Wiels, Wietse Chen, Hui Zhou Amin, Faisal Mohammad

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Migraine Non-CGRP targets Pituitary adenylate cyclase-activating polypeptide Vasoactive intestinal polypeptide Amylin Adrenomedullin Nitric oxide Phosphodiesterases Ion channels

Anmerkung:	© The Author(s) 2023

Übergeordnetes Werk:	Enthalten in: The journal of headache and pain - Milano : Springer Italia, 2000, 24(2023), 1 vom: 28. Juni
Übergeordnetes Werk:	volume:24 ; year:2023 ; number:1 ; day:28 ; month:06

Links:	Volltext

DOI / URN:	10.1186/s10194-023-01567-4

Katalog-ID:	SPR052063372

Internformat


LEADER	01000naa a22002652 4500
001	SPR052063372
003	DE-627
005	20230628064812.0
007	cr uuu---uuuuu
008	230628s2023 xx \|\|\|\|\|o 00\| \|\|eng c
024	7		\|a 10.1186/s10194-023-01567-4 \|2 doi
035			\|a (DE-627)SPR052063372
035			\|a (SPR)s10194-023-01567-4-e
040			\|a DE-627 \|b ger \|c DE-627 \|e rakwb
041			\|a eng
100	1		\|a Al-Hassany, Linda \|e verfasserin \|4 aut
245	1	0	\|a Future targets for migraine treatment beyond CGRP
264		1	\|c 2023
336			\|a Text \|b txt \|2 rdacontent
337			\|a Computermedien \|b c \|2 rdamedia
338			\|a Online-Ressource \|b cr \|2 rdacarrier
500			\|a © The Author(s) 2023
520			\|a Background Migraine is a disabling and chronic neurovascular headache disorder. Trigeminal vascular activation and release of calcitonin gene-related peptide (CGRP) play a pivotal role in the pathogenesis of migraine. This knowledge has led to the development of CGRP(-receptor) therapies. Yet, a substantial proportion of patients do not respond to these treatments. Therefore, alternative targets for future therapies are warranted. The current narrative review provides a comprehensive overview of the pathophysiological role of these possible non-CGRP targets in migraine. Findings We covered targets of the metabotropic receptors (pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), amylin, and adrenomedullin), intracellular targets (nitric oxide (NO), phosphodiesterase-3 (PDE3) and -5 (PDE5)), and ion channels (potassium, calcium, transient receptor potential (TRP), and acid-sensing ion channels (ASIC)). The majority of non-CGRP targets were able to induce migraine-like attacks, except for (i) calcium channels, as it is not yet possible to directly target channels to elucidate their precise involvement in migraine; (ii) TRP channels, activation of which can induce non-migraine headache; and (iii) ASICs, as their potential in inducing migraine attacks has not been investigated thus far. Drugs that target its receptors exist for PACAP, NO, and the potassium, TRP, and ASIC channels. No selective drugs exist for the other targets, however, some existing (migraine) treatments appear to indirectly antagonize responses to amylin, adrenomedullin, and calcium channels. Drugs against PACAP, NO, potassium channels, TRP channels, and only a $ PAC_{1} $ antibody have been tested for migraine treatment, albeit with ambiguous results. Conclusion While current research on these non-CGRP drug targets has not yet led to the development of efficacious therapies, human provocation studies using these targets have provided valuable insight into underlying mechanisms of migraine headaches and auras. Further studies are needed on these alternative therapies in non-responders of CGRP(-receptor) targeted therapies with the ultimate aim to pave the way towards a headache-free future for all migraine patients.
650		4	\|a Migraine \|7 (dpeaa)DE-He213
650		4	\|a Non-CGRP targets \|7 (dpeaa)DE-He213
650		4	\|a Pituitary adenylate cyclase-activating polypeptide \|7 (dpeaa)DE-He213
650		4	\|a Vasoactive intestinal polypeptide \|7 (dpeaa)DE-He213
650		4	\|a Amylin \|7 (dpeaa)DE-He213
650		4	\|a Adrenomedullin \|7 (dpeaa)DE-He213
650		4	\|a Nitric oxide \|7 (dpeaa)DE-He213
650		4	\|a Phosphodiesterases \|7 (dpeaa)DE-He213
650		4	\|a Ion channels \|7 (dpeaa)DE-He213
700	1		\|a Boucherie, Deirdre M. \|4 aut
700	1		\|a Creeney, Hannah \|4 aut
700	1		\|a van Drie, Ruben W. A. \|4 aut
700	1		\|a Farham, Fatemeh \|4 aut
700	1		\|a Favaretto, Silvia \|4 aut
700	1		\|a Gollion, Cédric \|4 aut
700	1		\|a Grangeon, Lou \|4 aut
700	1		\|a Lyons, Hannah \|4 aut
700	1		\|a Marschollek, Karol \|4 aut
700	1		\|a Onan, Dilara \|4 aut
700	1		\|a Pensato, Umberto \|4 aut
700	1		\|a Stanyer, Emily \|4 aut
700	1		\|a Waliszewska-Prosół, Marta \|4 aut
700	1		\|a Wiels, Wietse \|4 aut
700	1		\|a Chen, Hui Zhou \|4 aut
700	1		\|a Amin, Faisal Mohammad \|4 aut
773	0	8	\|i Enthalten in \|t The journal of headache and pain \|d Milano : Springer Italia, 2000 \|g 24(2023), 1 vom: 28. Juni \|w (DE-627)320600963 \|w (DE-600)2020168-0 \|x 1129-2377 \|7 nnns
773	1	8	\|g volume:24 \|g year:2023 \|g number:1 \|g day:28 \|g month:06
856	4	0	\|u https://dx.doi.org/10.1186/s10194-023-01567-4 \|z kostenfrei \|3 Volltext
912			\|a GBV_USEFLAG_A
912			\|a SYSFLAG_A
912			\|a GBV_SPRINGER
912			\|a GBV_ILN_20
912			\|a GBV_ILN_22
912			\|a GBV_ILN_23
912			\|a GBV_ILN_24
912			\|a GBV_ILN_31
912			\|a GBV_ILN_39
912			\|a GBV_ILN_40
912			\|a GBV_ILN_60
912			\|a GBV_ILN_62
912			\|a GBV_ILN_63
912			\|a GBV_ILN_69
912			\|a GBV_ILN_73
912			\|a GBV_ILN_74
912			\|a GBV_ILN_95
912			\|a GBV_ILN_105
912			\|a GBV_ILN_110
912			\|a GBV_ILN_151
912			\|a GBV_ILN_161
912			\|a GBV_ILN_170
912			\|a GBV_ILN_206
912			\|a GBV_ILN_213
912			\|a GBV_ILN_230
912			\|a GBV_ILN_267
912			\|a GBV_ILN_285
912			\|a GBV_ILN_293
912			\|a GBV_ILN_602
912			\|a GBV_ILN_2014
912			\|a GBV_ILN_2153
912			\|a GBV_ILN_4012
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4112
912			\|a GBV_ILN_4125
912			\|a GBV_ILN_4126
912			\|a GBV_ILN_4249
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4306
912			\|a GBV_ILN_4307
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4322
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4367
912			\|a GBV_ILN_4700
951			\|a AR
952			\|d 24 \|j 2023 \|e 1 \|b 28 \|c 06

Indexfelder

author_variant	l a h lah d m b dm dmb h c hc d r w a v drwa drwav f f ff s f sf c g cg l g lg h l hl k m km d o do u p up e s es m w p mwp w w ww h z c hz hzc f m a fm fma
matchkey_str	article:11292377:2023----::uueagtfririeram
hierarchy_sort_str	2023
publishDate	2023
allfields	10.1186/s10194-023-01567-4 doi (DE-627)SPR052063372 (SPR)s10194-023-01567-4-e DE-627 ger DE-627 rakwb eng Al-Hassany, Linda verfasserin aut Future targets for migraine treatment beyond CGRP 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Migraine is a disabling and chronic neurovascular headache disorder. Trigeminal vascular activation and release of calcitonin gene-related peptide (CGRP) play a pivotal role in the pathogenesis of migraine. This knowledge has led to the development of CGRP(-receptor) therapies. Yet, a substantial proportion of patients do not respond to these treatments. Therefore, alternative targets for future therapies are warranted. The current narrative review provides a comprehensive overview of the pathophysiological role of these possible non-CGRP targets in migraine. Findings We covered targets of the metabotropic receptors (pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), amylin, and adrenomedullin), intracellular targets (nitric oxide (NO), phosphodiesterase-3 (PDE3) and -5 (PDE5)), and ion channels (potassium, calcium, transient receptor potential (TRP), and acid-sensing ion channels (ASIC)). The majority of non-CGRP targets were able to induce migraine-like attacks, except for (i) calcium channels, as it is not yet possible to directly target channels to elucidate their precise involvement in migraine; (ii) TRP channels, activation of which can induce non-migraine headache; and (iii) ASICs, as their potential in inducing migraine attacks has not been investigated thus far. Drugs that target its receptors exist for PACAP, NO, and the potassium, TRP, and ASIC channels. No selective drugs exist for the other targets, however, some existing (migraine) treatments appear to indirectly antagonize responses to amylin, adrenomedullin, and calcium channels. Drugs against PACAP, NO, potassium channels, TRP channels, and only a $ PAC_{1} $ antibody have been tested for migraine treatment, albeit with ambiguous results. Conclusion While current research on these non-CGRP drug targets has not yet led to the development of efficacious therapies, human provocation studies using these targets have provided valuable insight into underlying mechanisms of migraine headaches and auras. Further studies are needed on these alternative therapies in non-responders of CGRP(-receptor) targeted therapies with the ultimate aim to pave the way towards a headache-free future for all migraine patients. Migraine (dpeaa)DE-He213 Non-CGRP targets (dpeaa)DE-He213 Pituitary adenylate cyclase-activating polypeptide (dpeaa)DE-He213 Vasoactive intestinal polypeptide (dpeaa)DE-He213 Amylin (dpeaa)DE-He213 Adrenomedullin (dpeaa)DE-He213 Nitric oxide (dpeaa)DE-He213 Phosphodiesterases (dpeaa)DE-He213 Ion channels (dpeaa)DE-He213 Boucherie, Deirdre M. aut Creeney, Hannah aut van Drie, Ruben W. A. aut Farham, Fatemeh aut Favaretto, Silvia aut Gollion, Cédric aut Grangeon, Lou aut Lyons, Hannah aut Marschollek, Karol aut Onan, Dilara aut Pensato, Umberto aut Stanyer, Emily aut Waliszewska-Prosół, Marta aut Wiels, Wietse aut Chen, Hui Zhou aut Amin, Faisal Mohammad aut Enthalten in The journal of headache and pain Milano : Springer Italia, 2000 24(2023), 1 vom: 28. Juni (DE-627)320600963 (DE-600)2020168-0 1129-2377 nnns volume:24 year:2023 number:1 day:28 month:06 https://dx.doi.org/10.1186/s10194-023-01567-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 1 28 06
spelling	10.1186/s10194-023-01567-4 doi (DE-627)SPR052063372 (SPR)s10194-023-01567-4-e DE-627 ger DE-627 rakwb eng Al-Hassany, Linda verfasserin aut Future targets for migraine treatment beyond CGRP 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Migraine is a disabling and chronic neurovascular headache disorder. Trigeminal vascular activation and release of calcitonin gene-related peptide (CGRP) play a pivotal role in the pathogenesis of migraine. This knowledge has led to the development of CGRP(-receptor) therapies. Yet, a substantial proportion of patients do not respond to these treatments. Therefore, alternative targets for future therapies are warranted. The current narrative review provides a comprehensive overview of the pathophysiological role of these possible non-CGRP targets in migraine. Findings We covered targets of the metabotropic receptors (pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), amylin, and adrenomedullin), intracellular targets (nitric oxide (NO), phosphodiesterase-3 (PDE3) and -5 (PDE5)), and ion channels (potassium, calcium, transient receptor potential (TRP), and acid-sensing ion channels (ASIC)). The majority of non-CGRP targets were able to induce migraine-like attacks, except for (i) calcium channels, as it is not yet possible to directly target channels to elucidate their precise involvement in migraine; (ii) TRP channels, activation of which can induce non-migraine headache; and (iii) ASICs, as their potential in inducing migraine attacks has not been investigated thus far. Drugs that target its receptors exist for PACAP, NO, and the potassium, TRP, and ASIC channels. No selective drugs exist for the other targets, however, some existing (migraine) treatments appear to indirectly antagonize responses to amylin, adrenomedullin, and calcium channels. Drugs against PACAP, NO, potassium channels, TRP channels, and only a $ PAC_{1} $ antibody have been tested for migraine treatment, albeit with ambiguous results. Conclusion While current research on these non-CGRP drug targets has not yet led to the development of efficacious therapies, human provocation studies using these targets have provided valuable insight into underlying mechanisms of migraine headaches and auras. Further studies are needed on these alternative therapies in non-responders of CGRP(-receptor) targeted therapies with the ultimate aim to pave the way towards a headache-free future for all migraine patients. Migraine (dpeaa)DE-He213 Non-CGRP targets (dpeaa)DE-He213 Pituitary adenylate cyclase-activating polypeptide (dpeaa)DE-He213 Vasoactive intestinal polypeptide (dpeaa)DE-He213 Amylin (dpeaa)DE-He213 Adrenomedullin (dpeaa)DE-He213 Nitric oxide (dpeaa)DE-He213 Phosphodiesterases (dpeaa)DE-He213 Ion channels (dpeaa)DE-He213 Boucherie, Deirdre M. aut Creeney, Hannah aut van Drie, Ruben W. A. aut Farham, Fatemeh aut Favaretto, Silvia aut Gollion, Cédric aut Grangeon, Lou aut Lyons, Hannah aut Marschollek, Karol aut Onan, Dilara aut Pensato, Umberto aut Stanyer, Emily aut Waliszewska-Prosół, Marta aut Wiels, Wietse aut Chen, Hui Zhou aut Amin, Faisal Mohammad aut Enthalten in The journal of headache and pain Milano : Springer Italia, 2000 24(2023), 1 vom: 28. Juni (DE-627)320600963 (DE-600)2020168-0 1129-2377 nnns volume:24 year:2023 number:1 day:28 month:06 https://dx.doi.org/10.1186/s10194-023-01567-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 1 28 06
allfields_unstemmed	10.1186/s10194-023-01567-4 doi (DE-627)SPR052063372 (SPR)s10194-023-01567-4-e DE-627 ger DE-627 rakwb eng Al-Hassany, Linda verfasserin aut Future targets for migraine treatment beyond CGRP 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Migraine is a disabling and chronic neurovascular headache disorder. Trigeminal vascular activation and release of calcitonin gene-related peptide (CGRP) play a pivotal role in the pathogenesis of migraine. This knowledge has led to the development of CGRP(-receptor) therapies. Yet, a substantial proportion of patients do not respond to these treatments. Therefore, alternative targets for future therapies are warranted. The current narrative review provides a comprehensive overview of the pathophysiological role of these possible non-CGRP targets in migraine. Findings We covered targets of the metabotropic receptors (pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), amylin, and adrenomedullin), intracellular targets (nitric oxide (NO), phosphodiesterase-3 (PDE3) and -5 (PDE5)), and ion channels (potassium, calcium, transient receptor potential (TRP), and acid-sensing ion channels (ASIC)). The majority of non-CGRP targets were able to induce migraine-like attacks, except for (i) calcium channels, as it is not yet possible to directly target channels to elucidate their precise involvement in migraine; (ii) TRP channels, activation of which can induce non-migraine headache; and (iii) ASICs, as their potential in inducing migraine attacks has not been investigated thus far. Drugs that target its receptors exist for PACAP, NO, and the potassium, TRP, and ASIC channels. No selective drugs exist for the other targets, however, some existing (migraine) treatments appear to indirectly antagonize responses to amylin, adrenomedullin, and calcium channels. Drugs against PACAP, NO, potassium channels, TRP channels, and only a $ PAC_{1} $ antibody have been tested for migraine treatment, albeit with ambiguous results. Conclusion While current research on these non-CGRP drug targets has not yet led to the development of efficacious therapies, human provocation studies using these targets have provided valuable insight into underlying mechanisms of migraine headaches and auras. Further studies are needed on these alternative therapies in non-responders of CGRP(-receptor) targeted therapies with the ultimate aim to pave the way towards a headache-free future for all migraine patients. Migraine (dpeaa)DE-He213 Non-CGRP targets (dpeaa)DE-He213 Pituitary adenylate cyclase-activating polypeptide (dpeaa)DE-He213 Vasoactive intestinal polypeptide (dpeaa)DE-He213 Amylin (dpeaa)DE-He213 Adrenomedullin (dpeaa)DE-He213 Nitric oxide (dpeaa)DE-He213 Phosphodiesterases (dpeaa)DE-He213 Ion channels (dpeaa)DE-He213 Boucherie, Deirdre M. aut Creeney, Hannah aut van Drie, Ruben W. A. aut Farham, Fatemeh aut Favaretto, Silvia aut Gollion, Cédric aut Grangeon, Lou aut Lyons, Hannah aut Marschollek, Karol aut Onan, Dilara aut Pensato, Umberto aut Stanyer, Emily aut Waliszewska-Prosół, Marta aut Wiels, Wietse aut Chen, Hui Zhou aut Amin, Faisal Mohammad aut Enthalten in The journal of headache and pain Milano : Springer Italia, 2000 24(2023), 1 vom: 28. Juni (DE-627)320600963 (DE-600)2020168-0 1129-2377 nnns volume:24 year:2023 number:1 day:28 month:06 https://dx.doi.org/10.1186/s10194-023-01567-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 1 28 06
allfieldsGer	10.1186/s10194-023-01567-4 doi (DE-627)SPR052063372 (SPR)s10194-023-01567-4-e DE-627 ger DE-627 rakwb eng Al-Hassany, Linda verfasserin aut Future targets for migraine treatment beyond CGRP 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Migraine is a disabling and chronic neurovascular headache disorder. Trigeminal vascular activation and release of calcitonin gene-related peptide (CGRP) play a pivotal role in the pathogenesis of migraine. This knowledge has led to the development of CGRP(-receptor) therapies. Yet, a substantial proportion of patients do not respond to these treatments. Therefore, alternative targets for future therapies are warranted. The current narrative review provides a comprehensive overview of the pathophysiological role of these possible non-CGRP targets in migraine. Findings We covered targets of the metabotropic receptors (pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), amylin, and adrenomedullin), intracellular targets (nitric oxide (NO), phosphodiesterase-3 (PDE3) and -5 (PDE5)), and ion channels (potassium, calcium, transient receptor potential (TRP), and acid-sensing ion channels (ASIC)). The majority of non-CGRP targets were able to induce migraine-like attacks, except for (i) calcium channels, as it is not yet possible to directly target channels to elucidate their precise involvement in migraine; (ii) TRP channels, activation of which can induce non-migraine headache; and (iii) ASICs, as their potential in inducing migraine attacks has not been investigated thus far. Drugs that target its receptors exist for PACAP, NO, and the potassium, TRP, and ASIC channels. No selective drugs exist for the other targets, however, some existing (migraine) treatments appear to indirectly antagonize responses to amylin, adrenomedullin, and calcium channels. Drugs against PACAP, NO, potassium channels, TRP channels, and only a $ PAC_{1} $ antibody have been tested for migraine treatment, albeit with ambiguous results. Conclusion While current research on these non-CGRP drug targets has not yet led to the development of efficacious therapies, human provocation studies using these targets have provided valuable insight into underlying mechanisms of migraine headaches and auras. Further studies are needed on these alternative therapies in non-responders of CGRP(-receptor) targeted therapies with the ultimate aim to pave the way towards a headache-free future for all migraine patients. Migraine (dpeaa)DE-He213 Non-CGRP targets (dpeaa)DE-He213 Pituitary adenylate cyclase-activating polypeptide (dpeaa)DE-He213 Vasoactive intestinal polypeptide (dpeaa)DE-He213 Amylin (dpeaa)DE-He213 Adrenomedullin (dpeaa)DE-He213 Nitric oxide (dpeaa)DE-He213 Phosphodiesterases (dpeaa)DE-He213 Ion channels (dpeaa)DE-He213 Boucherie, Deirdre M. aut Creeney, Hannah aut van Drie, Ruben W. A. aut Farham, Fatemeh aut Favaretto, Silvia aut Gollion, Cédric aut Grangeon, Lou aut Lyons, Hannah aut Marschollek, Karol aut Onan, Dilara aut Pensato, Umberto aut Stanyer, Emily aut Waliszewska-Prosół, Marta aut Wiels, Wietse aut Chen, Hui Zhou aut Amin, Faisal Mohammad aut Enthalten in The journal of headache and pain Milano : Springer Italia, 2000 24(2023), 1 vom: 28. Juni (DE-627)320600963 (DE-600)2020168-0 1129-2377 nnns volume:24 year:2023 number:1 day:28 month:06 https://dx.doi.org/10.1186/s10194-023-01567-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 1 28 06
allfieldsSound	10.1186/s10194-023-01567-4 doi (DE-627)SPR052063372 (SPR)s10194-023-01567-4-e DE-627 ger DE-627 rakwb eng Al-Hassany, Linda verfasserin aut Future targets for migraine treatment beyond CGRP 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Migraine is a disabling and chronic neurovascular headache disorder. Trigeminal vascular activation and release of calcitonin gene-related peptide (CGRP) play a pivotal role in the pathogenesis of migraine. This knowledge has led to the development of CGRP(-receptor) therapies. Yet, a substantial proportion of patients do not respond to these treatments. Therefore, alternative targets for future therapies are warranted. The current narrative review provides a comprehensive overview of the pathophysiological role of these possible non-CGRP targets in migraine. Findings We covered targets of the metabotropic receptors (pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), amylin, and adrenomedullin), intracellular targets (nitric oxide (NO), phosphodiesterase-3 (PDE3) and -5 (PDE5)), and ion channels (potassium, calcium, transient receptor potential (TRP), and acid-sensing ion channels (ASIC)). The majority of non-CGRP targets were able to induce migraine-like attacks, except for (i) calcium channels, as it is not yet possible to directly target channels to elucidate their precise involvement in migraine; (ii) TRP channels, activation of which can induce non-migraine headache; and (iii) ASICs, as their potential in inducing migraine attacks has not been investigated thus far. Drugs that target its receptors exist for PACAP, NO, and the potassium, TRP, and ASIC channels. No selective drugs exist for the other targets, however, some existing (migraine) treatments appear to indirectly antagonize responses to amylin, adrenomedullin, and calcium channels. Drugs against PACAP, NO, potassium channels, TRP channels, and only a $ PAC_{1} $ antibody have been tested for migraine treatment, albeit with ambiguous results. Conclusion While current research on these non-CGRP drug targets has not yet led to the development of efficacious therapies, human provocation studies using these targets have provided valuable insight into underlying mechanisms of migraine headaches and auras. Further studies are needed on these alternative therapies in non-responders of CGRP(-receptor) targeted therapies with the ultimate aim to pave the way towards a headache-free future for all migraine patients. Migraine (dpeaa)DE-He213 Non-CGRP targets (dpeaa)DE-He213 Pituitary adenylate cyclase-activating polypeptide (dpeaa)DE-He213 Vasoactive intestinal polypeptide (dpeaa)DE-He213 Amylin (dpeaa)DE-He213 Adrenomedullin (dpeaa)DE-He213 Nitric oxide (dpeaa)DE-He213 Phosphodiesterases (dpeaa)DE-He213 Ion channels (dpeaa)DE-He213 Boucherie, Deirdre M. aut Creeney, Hannah aut van Drie, Ruben W. A. aut Farham, Fatemeh aut Favaretto, Silvia aut Gollion, Cédric aut Grangeon, Lou aut Lyons, Hannah aut Marschollek, Karol aut Onan, Dilara aut Pensato, Umberto aut Stanyer, Emily aut Waliszewska-Prosół, Marta aut Wiels, Wietse aut Chen, Hui Zhou aut Amin, Faisal Mohammad aut Enthalten in The journal of headache and pain Milano : Springer Italia, 2000 24(2023), 1 vom: 28. Juni (DE-627)320600963 (DE-600)2020168-0 1129-2377 nnns volume:24 year:2023 number:1 day:28 month:06 https://dx.doi.org/10.1186/s10194-023-01567-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 1 28 06
language	English
source	Enthalten in The journal of headache and pain 24(2023), 1 vom: 28. Juni volume:24 year:2023 number:1 day:28 month:06
sourceStr	Enthalten in The journal of headache and pain 24(2023), 1 vom: 28. Juni volume:24 year:2023 number:1 day:28 month:06
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Migraine Non-CGRP targets Pituitary adenylate cyclase-activating polypeptide Vasoactive intestinal polypeptide Amylin Adrenomedullin Nitric oxide Phosphodiesterases Ion channels
isfreeaccess_bool	true
container_title	The journal of headache and pain
authorswithroles_txt_mv	Al-Hassany, Linda @@aut@@ Boucherie, Deirdre M. @@aut@@ Creeney, Hannah @@aut@@ van Drie, Ruben W. A. @@aut@@ Farham, Fatemeh @@aut@@ Favaretto, Silvia @@aut@@ Gollion, Cédric @@aut@@ Grangeon, Lou @@aut@@ Lyons, Hannah @@aut@@ Marschollek, Karol @@aut@@ Onan, Dilara @@aut@@ Pensato, Umberto @@aut@@ Stanyer, Emily @@aut@@ Waliszewska-Prosół, Marta @@aut@@ Wiels, Wietse @@aut@@ Chen, Hui Zhou @@aut@@ Amin, Faisal Mohammad @@aut@@
publishDateDaySort_date	2023-06-28T00:00:00Z
hierarchy_top_id	320600963
id	SPR052063372
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">SPR052063372</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230628064812.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230628s2023 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s10194-023-01567-4</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR052063372</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s10194-023-01567-4-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Al-Hassany, Linda</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Future targets for migraine treatment beyond CGRP</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2023</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s) 2023</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background Migraine is a disabling and chronic neurovascular headache disorder. Trigeminal vascular activation and release of calcitonin gene-related peptide (CGRP) play a pivotal role in the pathogenesis of migraine. This knowledge has led to the development of CGRP(-receptor) therapies. Yet, a substantial proportion of patients do not respond to these treatments. Therefore, alternative targets for future therapies are warranted. The current narrative review provides a comprehensive overview of the pathophysiological role of these possible non-CGRP targets in migraine. Findings We covered targets of the metabotropic receptors (pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), amylin, and adrenomedullin), intracellular targets (nitric oxide (NO), phosphodiesterase-3 (PDE3) and -5 (PDE5)), and ion channels (potassium, calcium, transient receptor potential (TRP), and acid-sensing ion channels (ASIC)). The majority of non-CGRP targets were able to induce migraine-like attacks, except for (i) calcium channels, as it is not yet possible to directly target channels to elucidate their precise involvement in migraine; (ii) TRP channels, activation of which can induce non-migraine headache; and (iii) ASICs, as their potential in inducing migraine attacks has not been investigated thus far. Drugs that target its receptors exist for PACAP, NO, and the potassium, TRP, and ASIC channels. No selective drugs exist for the other targets, however, some existing (migraine) treatments appear to indirectly antagonize responses to amylin, adrenomedullin, and calcium channels. Drugs against PACAP, NO, potassium channels, TRP channels, and only a $ PAC_{1} $ antibody have been tested for migraine treatment, albeit with ambiguous results. Conclusion While current research on these non-CGRP drug targets has not yet led to the development of efficacious therapies, human provocation studies using these targets have provided valuable insight into underlying mechanisms of migraine headaches and auras. Further studies are needed on these alternative therapies in non-responders of CGRP(-receptor) targeted therapies with the ultimate aim to pave the way towards a headache-free future for all migraine patients.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Migraine</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Non-CGRP targets</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pituitary adenylate cyclase-activating polypeptide</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Vasoactive intestinal polypeptide</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Amylin</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Adrenomedullin</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Nitric oxide</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Phosphodiesterases</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Ion channels</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Boucherie, Deirdre M.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Creeney, Hannah</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">van Drie, Ruben W. A.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Farham, Fatemeh</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Favaretto, Silvia</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Gollion, Cédric</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Grangeon, Lou</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Lyons, Hannah</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Marschollek, Karol</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Onan, Dilara</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Pensato, Umberto</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Stanyer, Emily</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Waliszewska-Prosół, Marta</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wiels, Wietse</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Chen, Hui Zhou</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Amin, Faisal Mohammad</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">The journal of headache and pain</subfield><subfield code="d">Milano : Springer Italia, 2000</subfield><subfield code="g">24(2023), 1 vom: 28. Juni</subfield><subfield code="w">(DE-627)320600963</subfield><subfield code="w">(DE-600)2020168-0</subfield><subfield code="x">1129-2377</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:24</subfield><subfield code="g">year:2023</subfield><subfield code="g">number:1</subfield><subfield code="g">day:28</subfield><subfield code="g">month:06</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://dx.doi.org/10.1186/s10194-023-01567-4</subfield><subfield code="z">kostenfrei</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_SPRINGER</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_267</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2153</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">24</subfield><subfield code="j">2023</subfield><subfield code="e">1</subfield><subfield code="b">28</subfield><subfield code="c">06</subfield></datafield></record></collection>
author	Al-Hassany, Linda
spellingShingle	Al-Hassany, Linda misc Migraine misc Non-CGRP targets misc Pituitary adenylate cyclase-activating polypeptide misc Vasoactive intestinal polypeptide misc Amylin misc Adrenomedullin misc Nitric oxide misc Phosphodiesterases misc Ion channels Future targets for migraine treatment beyond CGRP
authorStr	Al-Hassany, Linda
ppnlink_with_tag_str_mv	@@773@@(DE-627)320600963
format	electronic Article
delete_txt_mv	keep
author_role	aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut
collection	springer
remote_str	true
illustrated	Not Illustrated
issn	1129-2377
topic_title	Future targets for migraine treatment beyond CGRP Migraine (dpeaa)DE-He213 Non-CGRP targets (dpeaa)DE-He213 Pituitary adenylate cyclase-activating polypeptide (dpeaa)DE-He213 Vasoactive intestinal polypeptide (dpeaa)DE-He213 Amylin (dpeaa)DE-He213 Adrenomedullin (dpeaa)DE-He213 Nitric oxide (dpeaa)DE-He213 Phosphodiesterases (dpeaa)DE-He213 Ion channels (dpeaa)DE-He213
topic	misc Migraine misc Non-CGRP targets misc Pituitary adenylate cyclase-activating polypeptide misc Vasoactive intestinal polypeptide misc Amylin misc Adrenomedullin misc Nitric oxide misc Phosphodiesterases misc Ion channels
topic_unstemmed	misc Migraine misc Non-CGRP targets misc Pituitary adenylate cyclase-activating polypeptide misc Vasoactive intestinal polypeptide misc Amylin misc Adrenomedullin misc Nitric oxide misc Phosphodiesterases misc Ion channels
topic_browse	misc Migraine misc Non-CGRP targets misc Pituitary adenylate cyclase-activating polypeptide misc Vasoactive intestinal polypeptide misc Amylin misc Adrenomedullin misc Nitric oxide misc Phosphodiesterases misc Ion channels
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
format_main_str_mv	Text Zeitschrift/Artikel
carriertype_str_mv	cr
hierarchy_parent_title	The journal of headache and pain
hierarchy_parent_id	320600963
hierarchy_top_title	The journal of headache and pain
isfreeaccess_txt	true
familylinks_str_mv	(DE-627)320600963 (DE-600)2020168-0
title	Future targets for migraine treatment beyond CGRP
ctrlnum	(DE-627)SPR052063372 (SPR)s10194-023-01567-4-e
title_full	Future targets for migraine treatment beyond CGRP
author_sort	Al-Hassany, Linda
journal	The journal of headache and pain
journalStr	The journal of headache and pain
lang_code	eng
isOA_bool	true
recordtype	marc
publishDateSort	2023
contenttype_str_mv	txt
author_browse	Al-Hassany, Linda Boucherie, Deirdre M. Creeney, Hannah van Drie, Ruben W. A. Farham, Fatemeh Favaretto, Silvia Gollion, Cédric Grangeon, Lou Lyons, Hannah Marschollek, Karol Onan, Dilara Pensato, Umberto Stanyer, Emily Waliszewska-Prosół, Marta Wiels, Wietse Chen, Hui Zhou Amin, Faisal Mohammad
container_volume	24
format_se	Elektronische Aufsätze
author-letter	Al-Hassany, Linda
doi_str_mv	10.1186/s10194-023-01567-4
title_sort	future targets for migraine treatment beyond cgrp
title_auth	Future targets for migraine treatment beyond CGRP
abstract	Background Migraine is a disabling and chronic neurovascular headache disorder. Trigeminal vascular activation and release of calcitonin gene-related peptide (CGRP) play a pivotal role in the pathogenesis of migraine. This knowledge has led to the development of CGRP(-receptor) therapies. Yet, a substantial proportion of patients do not respond to these treatments. Therefore, alternative targets for future therapies are warranted. The current narrative review provides a comprehensive overview of the pathophysiological role of these possible non-CGRP targets in migraine. Findings We covered targets of the metabotropic receptors (pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), amylin, and adrenomedullin), intracellular targets (nitric oxide (NO), phosphodiesterase-3 (PDE3) and -5 (PDE5)), and ion channels (potassium, calcium, transient receptor potential (TRP), and acid-sensing ion channels (ASIC)). The majority of non-CGRP targets were able to induce migraine-like attacks, except for (i) calcium channels, as it is not yet possible to directly target channels to elucidate their precise involvement in migraine; (ii) TRP channels, activation of which can induce non-migraine headache; and (iii) ASICs, as their potential in inducing migraine attacks has not been investigated thus far. Drugs that target its receptors exist for PACAP, NO, and the potassium, TRP, and ASIC channels. No selective drugs exist for the other targets, however, some existing (migraine) treatments appear to indirectly antagonize responses to amylin, adrenomedullin, and calcium channels. Drugs against PACAP, NO, potassium channels, TRP channels, and only a $ PAC_{1} $ antibody have been tested for migraine treatment, albeit with ambiguous results. Conclusion While current research on these non-CGRP drug targets has not yet led to the development of efficacious therapies, human provocation studies using these targets have provided valuable insight into underlying mechanisms of migraine headaches and auras. Further studies are needed on these alternative therapies in non-responders of CGRP(-receptor) targeted therapies with the ultimate aim to pave the way towards a headache-free future for all migraine patients. © The Author(s) 2023
abstractGer	Background Migraine is a disabling and chronic neurovascular headache disorder. Trigeminal vascular activation and release of calcitonin gene-related peptide (CGRP) play a pivotal role in the pathogenesis of migraine. This knowledge has led to the development of CGRP(-receptor) therapies. Yet, a substantial proportion of patients do not respond to these treatments. Therefore, alternative targets for future therapies are warranted. The current narrative review provides a comprehensive overview of the pathophysiological role of these possible non-CGRP targets in migraine. Findings We covered targets of the metabotropic receptors (pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), amylin, and adrenomedullin), intracellular targets (nitric oxide (NO), phosphodiesterase-3 (PDE3) and -5 (PDE5)), and ion channels (potassium, calcium, transient receptor potential (TRP), and acid-sensing ion channels (ASIC)). The majority of non-CGRP targets were able to induce migraine-like attacks, except for (i) calcium channels, as it is not yet possible to directly target channels to elucidate their precise involvement in migraine; (ii) TRP channels, activation of which can induce non-migraine headache; and (iii) ASICs, as their potential in inducing migraine attacks has not been investigated thus far. Drugs that target its receptors exist for PACAP, NO, and the potassium, TRP, and ASIC channels. No selective drugs exist for the other targets, however, some existing (migraine) treatments appear to indirectly antagonize responses to amylin, adrenomedullin, and calcium channels. Drugs against PACAP, NO, potassium channels, TRP channels, and only a $ PAC_{1} $ antibody have been tested for migraine treatment, albeit with ambiguous results. Conclusion While current research on these non-CGRP drug targets has not yet led to the development of efficacious therapies, human provocation studies using these targets have provided valuable insight into underlying mechanisms of migraine headaches and auras. Further studies are needed on these alternative therapies in non-responders of CGRP(-receptor) targeted therapies with the ultimate aim to pave the way towards a headache-free future for all migraine patients. © The Author(s) 2023
abstract_unstemmed	Background Migraine is a disabling and chronic neurovascular headache disorder. Trigeminal vascular activation and release of calcitonin gene-related peptide (CGRP) play a pivotal role in the pathogenesis of migraine. This knowledge has led to the development of CGRP(-receptor) therapies. Yet, a substantial proportion of patients do not respond to these treatments. Therefore, alternative targets for future therapies are warranted. The current narrative review provides a comprehensive overview of the pathophysiological role of these possible non-CGRP targets in migraine. Findings We covered targets of the metabotropic receptors (pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), amylin, and adrenomedullin), intracellular targets (nitric oxide (NO), phosphodiesterase-3 (PDE3) and -5 (PDE5)), and ion channels (potassium, calcium, transient receptor potential (TRP), and acid-sensing ion channels (ASIC)). The majority of non-CGRP targets were able to induce migraine-like attacks, except for (i) calcium channels, as it is not yet possible to directly target channels to elucidate their precise involvement in migraine; (ii) TRP channels, activation of which can induce non-migraine headache; and (iii) ASICs, as their potential in inducing migraine attacks has not been investigated thus far. Drugs that target its receptors exist for PACAP, NO, and the potassium, TRP, and ASIC channels. No selective drugs exist for the other targets, however, some existing (migraine) treatments appear to indirectly antagonize responses to amylin, adrenomedullin, and calcium channels. Drugs against PACAP, NO, potassium channels, TRP channels, and only a $ PAC_{1} $ antibody have been tested for migraine treatment, albeit with ambiguous results. Conclusion While current research on these non-CGRP drug targets has not yet led to the development of efficacious therapies, human provocation studies using these targets have provided valuable insight into underlying mechanisms of migraine headaches and auras. Further studies are needed on these alternative therapies in non-responders of CGRP(-receptor) targeted therapies with the ultimate aim to pave the way towards a headache-free future for all migraine patients. © The Author(s) 2023
collection_details	GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700
container_issue	1
title_short	Future targets for migraine treatment beyond CGRP
url	https://dx.doi.org/10.1186/s10194-023-01567-4
remote_bool	true
author2	Boucherie, Deirdre M. Creeney, Hannah van Drie, Ruben W. A. Farham, Fatemeh Favaretto, Silvia Gollion, Cédric Grangeon, Lou Lyons, Hannah Marschollek, Karol Onan, Dilara Pensato, Umberto Stanyer, Emily Waliszewska-Prosół, Marta Wiels, Wietse Chen, Hui Zhou Amin, Faisal Mohammad
author2Str	Boucherie, Deirdre M. Creeney, Hannah van Drie, Ruben W. A. Farham, Fatemeh Favaretto, Silvia Gollion, Cédric Grangeon, Lou Lyons, Hannah Marschollek, Karol Onan, Dilara Pensato, Umberto Stanyer, Emily Waliszewska-Prosół, Marta Wiels, Wietse Chen, Hui Zhou Amin, Faisal Mohammad
ppnlink	320600963
mediatype_str_mv	c
isOA_txt	true
hochschulschrift_bool	false
doi_str	10.1186/s10194-023-01567-4
up_date	2024-07-04T01:05:28.872Z
_version_	1803608526814183424
fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">SPR052063372</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230628064812.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230628s2023 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s10194-023-01567-4</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR052063372</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s10194-023-01567-4-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Al-Hassany, Linda</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Future targets for migraine treatment beyond CGRP</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2023</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s) 2023</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background Migraine is a disabling and chronic neurovascular headache disorder. Trigeminal vascular activation and release of calcitonin gene-related peptide (CGRP) play a pivotal role in the pathogenesis of migraine. This knowledge has led to the development of CGRP(-receptor) therapies. Yet, a substantial proportion of patients do not respond to these treatments. Therefore, alternative targets for future therapies are warranted. The current narrative review provides a comprehensive overview of the pathophysiological role of these possible non-CGRP targets in migraine. Findings We covered targets of the metabotropic receptors (pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), amylin, and adrenomedullin), intracellular targets (nitric oxide (NO), phosphodiesterase-3 (PDE3) and -5 (PDE5)), and ion channels (potassium, calcium, transient receptor potential (TRP), and acid-sensing ion channels (ASIC)). The majority of non-CGRP targets were able to induce migraine-like attacks, except for (i) calcium channels, as it is not yet possible to directly target channels to elucidate their precise involvement in migraine; (ii) TRP channels, activation of which can induce non-migraine headache; and (iii) ASICs, as their potential in inducing migraine attacks has not been investigated thus far. Drugs that target its receptors exist for PACAP, NO, and the potassium, TRP, and ASIC channels. No selective drugs exist for the other targets, however, some existing (migraine) treatments appear to indirectly antagonize responses to amylin, adrenomedullin, and calcium channels. Drugs against PACAP, NO, potassium channels, TRP channels, and only a $ PAC_{1} $ antibody have been tested for migraine treatment, albeit with ambiguous results. Conclusion While current research on these non-CGRP drug targets has not yet led to the development of efficacious therapies, human provocation studies using these targets have provided valuable insight into underlying mechanisms of migraine headaches and auras. Further studies are needed on these alternative therapies in non-responders of CGRP(-receptor) targeted therapies with the ultimate aim to pave the way towards a headache-free future for all migraine patients.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Migraine</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Non-CGRP targets</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pituitary adenylate cyclase-activating polypeptide</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Vasoactive intestinal polypeptide</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Amylin</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Adrenomedullin</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Nitric oxide</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Phosphodiesterases</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Ion channels</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Boucherie, Deirdre M.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Creeney, Hannah</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">van Drie, Ruben W. A.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Farham, Fatemeh</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Favaretto, Silvia</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Gollion, Cédric</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Grangeon, Lou</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Lyons, Hannah</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Marschollek, Karol</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Onan, Dilara</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Pensato, Umberto</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Stanyer, Emily</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Waliszewska-Prosół, Marta</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wiels, Wietse</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Chen, Hui Zhou</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Amin, Faisal Mohammad</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">The journal of headache and pain</subfield><subfield code="d">Milano : Springer Italia, 2000</subfield><subfield code="g">24(2023), 1 vom: 28. Juni</subfield><subfield code="w">(DE-627)320600963</subfield><subfield code="w">(DE-600)2020168-0</subfield><subfield code="x">1129-2377</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:24</subfield><subfield code="g">year:2023</subfield><subfield code="g">number:1</subfield><subfield code="g">day:28</subfield><subfield code="g">month:06</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://dx.doi.org/10.1186/s10194-023-01567-4</subfield><subfield code="z">kostenfrei</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_SPRINGER</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_267</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2153</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">24</subfield><subfield code="j">2023</subfield><subfield code="e">1</subfield><subfield code="b">28</subfield><subfield code="c">06</subfield></datafield></record></collection>
score	7.4012985

Nicht das Richtige dabei?

Schreiben Sie uns!

Future targets for migraine treatment beyond CGRP

Nicht das Richtige dabei?

Zugang & Verfügbarkeit

Vorhandene Bände

Nicht das Richtige dabei?