The 5-HT 1D Receptor Antagonist GR-127,935 Prevents Inhibitory Effects of Sumatriptan but not CP-122,288 and 5-CT on Neurogenic Plasma Extravasation within Guinea Pig Dura Mater

Yu, Xian Jie; Cutrer, F. Michael; Moskowitz, M. A.; Waeber, Christian

doi:10.1016/s0028-3908(96)00149-9

Cited by 43 publications

(24 citation statements)

References 31 publications

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“…In keeping with the above, Yu et al (1997) reported that GR127935 potently antagonised the inhibition of neurogenic plasma extravasation in the guinea pig by sumatriptan, but not by 5-carboxamidotryptamine.…”

Section: Contraction Induced By Antimigraine Drugssupporting

confidence: 70%

Bovine isolated middle cerebral artery contractions to antimigraine drugs

Roon¹,

MaassenVanDenBrink

Ferrari

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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Ergot alkaloids, sumatriptan and the newer 5-HT1B/1D receptor agonists all contract cranial blood vessels and this effect seems to be primarily responsible for their efficacy in migraine. We have compared the contractile effects of a number of ergot and triptan derivatives on the bovine isolated middle cerebral artery and characterised the 5-hydroxytryptamine (5-HT) receptors involved by using 5-HT2A (ketanserin: 10, 30, 100 nM) and 5-HT1B/1D (GR127935: 30, 100, 300 nM) receptor antagonists. The rank order of agonist potency (pD2) was ergotamine (8.0+/-0.1) approximately dihydroergotamine (8.0+/-0.1) > avitriptan (7.4+/-0.3) >5-HT (7.0+/-0.1) > naratriptan (6.8+/-0.1) > methylergometrine (major metabolite of methysergide; 6.5+/-0.2) > rizatriptan (6.3+/-0.3) approximately zolmitriptan (6.2+/-0.1) approximately sumatriptan (6.0+/-0.2) approximately methysergide (5.9+/-0.3). The rank order of efficacy (Emax expressed as % of contraction to 100 mM K+) was 5-HT (127+/-11) > sumatriptan (56+/-5) > ergotamine (48+/-5) approximately dihydroergotamine (44+/-8) approximately methyl-ergometrine (44+/-7) > avitriptan (37+/-7) approximately rizatriptan (33+/-5) approximately methysergide (29+/-10) approximately zolmitriptan (28+/-3) approximately naratriptan (23+/-2). The concentration-response curve to 5-HT appeared to be biphasic in the presence of 100 nM ketanserin, which hardly affected sumatriptan-induced contractions, but clearly antagonised the second more efficacious phase of the curve to 5-HT. On the other hand, GR127935 caused a rightward shift of the concentration-response curves to 5-HT (in the presence of 10 microM ketanserin) and sumatriptan with pA2 values of 7.0 and 8.1, respectively. In conclusion, all acutely acting antimigraine drugs contract the bovine isolated middle cerebral artery. Whereas sumatriptan contracts the artery via the 5-HT1B/1D receptor, the 5-HT-induced contraction is mediated partly by the 5-HT2A receptor and partly by another, possibly novel receptor differing from the 5-HT1B/1D receptor. This receptor may be a target for the development of future antimigraine drugs.

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Section: Contraction Induced By Antimigraine Drugssupporting

confidence: 70%

Bovine isolated middle cerebral artery contractions to antimigraine drugs

Roon¹,

MaassenVanDenBrink

Ferrari

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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“…The gp 5‐HT 1B receptor‐mediated [ 35 5S]‐GTPγS response was partially inhibited by GR 127935, thus extending previous observations (see Pauwels, 1997a) that GR 127935 produces partial intrinsic activity at 5‐HT 1B receptors. This characterization can also account for some in vivo data; Yu et al (1997) showed that GR 127935 acts as a partial antagonist of sumatriptan‐mediated inhibition of neurogenic plasma extravasion within guinea‐pig dura mater. Otherwise, methiothepin and SB224289 potently antagonized the 5‐HT response in a competitive manner.…”

Section: Discussionmentioning

confidence: 83%

Pharmacological analysis of G‐protein activation mediated by guinea‐pig recombinant 5‐HT_1B receptors in C6‐glial cells: similarities with the human 5‐HT_1B receptor

Pauwels

Wurch

Palmier

et al. 1998

British J Pharmacology

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1 The guinea-pig recombinant 5-hydroxytryptamine 1B (gp 5-HT 1B ) receptor stably transfected in rat C6-glial cells was characterized by monitoring G-protein activation in a membrane preparation with agoniststimulated [ , respectively when 5-HT was used as an agonist. These estimates accorded with the potencies measured in antagonism of zolmitriptan-mediated inhibition of forskolin-stimulated cyclic AMP formation. Ketanserin acted as a weak antagonist (pK B : 5.87) at gp 5-HT 1B receptors. 5 In conclusion, the recombinant gp 5-HT 1B receptor shares important pharmacological similarities with the recombinant h 5-HT 1B receptor. The ®nding that negative activity occurs at these receptors further suggests that SB224289, methiothepin and ritanserin are likely to be inverse agonists.

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“…Evans blue (a dye binding to albumin) allows real-time monitoring of dural extravasation with intravital microscopy and quantification of the leakage by spectrophotometry at the end of the experiment (Johnson and Phebus, 1998). Unlike dural vasodilatation, dural PPE is suppressed by clinically ineffective (neurokinin A and substance P inhibitors and endothelin blockers) as well as clinically effective (triptans and CGRP antagonists) agents (Moskowitz, 1992;O'Shaughnessy and Connor, 1994;Shepheard et al, 1995;May et al, 1996;Goldstein et al, 1997;Williamson et al, 1997c;Yu et al, 1997). has also been used to examine dural plasma extravasation ex vivo (Bolay et al, 2002;Figure 2).…”

Section: Neurogenic Inflammationmentioning

confidence: 99%

“…NK1 receptor antagonists on the other hand failed to inhibit dural vasodilatation and were also found to be clinically ineffective for migraine (Goldstein et al, 1997;Williamson et al, 1997b). Unlike dural vasodilatation, dural PPE is suppressed by clinically ineffective (neurokinin A and substance P inhibitors and endothelin blockers) as well as clinically effective (triptans and CGRP antagonists) agents (Moskowitz, 1992;O'Shaughnessy and Connor, 1994;Shepheard et al, 1995;May et al, 1996;Goldstein et al, 1997;Williamson et al, 1997c;Yu et al, 1997). These inconsistencies are further aggravated by species differences: for example, 5-HT1D receptor agonists more potently inhibit PPE in rats and guinea pigs (Shepherd et al, 1997), whereas 5-HT1B agonists are more potent in mice (Yu et al, 1996).…”

Section: Neurogenic Inflammationmentioning

confidence: 99%

Modelling headache and migraine and its pharmacological manipulation

Erdener

Dalkara

2014

British J Pharmacology

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Similarities between laboratory animals and humans in anatomy and physiology of the cephalic nociceptive pathways have allowed scientists to create successful models that have significantly contributed to our understanding of headache. They have also been instrumental in the development of novel anti-migraine drugs different from classical pain killers. Nevertheless, modelling the mechanisms underlying primary headache disorders like migraine has been challenging due to limitations in testing the postulated hypotheses in humans. Recent developments in imaging techniques have begun to fill this translational gap. The unambiguous demonstration of cortical spreading depolarization (CSD) during migraine aura in patients has reawakened interest in studying CSD in animals as a noxious brain event that can activate the trigeminovascular system. CSD-based models, including transgenics and optogenetics, may more realistically simulate pain generation in migraine, which is thought to originate within the brain. The realization that behavioural correlates of headache and migrainous symptoms like photophobia can be assessed quantitatively in laboratory animals, has created an opportunity to directly study the headache in intact animals without the confounding effects of anaesthetics. Headache and migraine-like episodes induced by administration of glyceryltrinitrate and CGRP to humans and parallel behavioural and biological changes observed in rodents create interesting possibilities for translational research. Not unexpectedly, species differences and model-specific observations have also led to controversies as well as disappointments in clinical trials, which, in return, has helped us improve the models and advance our understanding of headache. Here, we review commonly used headache and migraine models with an emphasis on recent developments.

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The 5-HT 1D Receptor Antagonist GR-127,935 Prevents Inhibitory Effects of Sumatriptan but not CP-122,288 and 5-CT on Neurogenic Plasma Extravasation within Guinea Pig Dura Mater

Cited by 43 publications

References 31 publications

Bovine isolated middle cerebral artery contractions to antimigraine drugs

Bovine isolated middle cerebral artery contractions to antimigraine drugs

Pharmacological analysis of G‐protein activation mediated by guinea‐pig recombinant 5‐HT_1B receptors in C6‐glial cells: similarities with the human 5‐HT_1B receptor

Modelling headache and migraine and its pharmacological manipulation

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The 5-HT 1D Receptor Antagonist GR-127,935 Prevents Inhibitory Effects of Sumatriptan but not CP-122,288 and 5-CT on Neurogenic Plasma Extravasation within Guinea Pig Dura Mater

Cited by 43 publications

References 31 publications

Bovine isolated middle cerebral artery contractions to antimigraine drugs

Bovine isolated middle cerebral artery contractions to antimigraine drugs

Pharmacological analysis of G‐protein activation mediated by guinea‐pig recombinant 5‐HT1B receptors in C6‐glial cells: similarities with the human 5‐HT1B receptor

Modelling headache and migraine and its pharmacological manipulation

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Product

Resources

About

Pharmacological analysis of G‐protein activation mediated by guinea‐pig recombinant 5‐HT_1B receptors in C6‐glial cells: similarities with the human 5‐HT_1B receptor