GR127935: a potent and selective 5-HT1D receptor antagonist

Skingle, M.; Beattie, David T.; Scopes, Dic; Starkey, Sarah J.; Connor, Helen E.; Feniuk, W.; Tyers, M.B.

doi:10.1016/0166-4328(96)00089-7

Cited by 187 publications

(198 citation statements)

References 17 publications

Supporting

Mentioning

186

Contrasting

Order By: Relevance

“…Taking into account that sumatriptan (Peroutka and McCarthy, 1989;Schoeffter and Hoyer, 1989;, GMC2021 (K. Svensson, unpublished observations) as well as GR127935 (Clitherow et al, 1994;Skingle et al, 1993;Pauwels and Colpaert, 1995;Watson et al, 1995) have high affinities for 5-HT1D receptors, our results suggest that the GMC2021-induced constriction of carotid arteriovenous anastomoses is partly mediated by 5-HT1D receptors, reinforcing the view that 5-HT~-like and 5-HT1D receptors may be identical. Although none of these compounds distinguish between 5-HT~o ~ and 5-HT~D ~ subtypes, the presence of the 5-HT~D a mRNA, but not 5-HT~D ~ receptor mRNA, in human and bovine cerebral arteries (Hamel et al, 1993) indicates that the 5-HT~D ~ receptor mediates contractile responses in cranial vessels.…”

Section: Systemic Haemodynamic Changessupporting

confidence: 78%

“…Evidence is now emerging that this vascular 5-HTl-like receptor may be identical to the recombinant 5-HTtD, most probably 5-HT1Dt3 , receptor. Thus, the mRNA for the 5-HT~D ~, but not that for 5-HT1D~, receptor is present in cranial blood vessels (Hamel et al, 1993) and the vasoconstriction by sumatriptan, which has a high affinity for 5-HT m receptors (Peroutka and McCarthy, 1989;Beattie et al, 1994), is antagonized by GR127935, a selective I H 5-HTID receptor antagonist (Skingle et al, 1993;Clitherow et al, 1994;De Vries et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Investigations with GMC2021 in experimental models predictive of antimigraine activity and coronary side-effect potential

Saxena

Heiligers

VanDenBrink

et al. 1996

European Journal of Pharmacology

View full text Add to dashboard Cite

Several acutely acting antimigraine drugs, including sumatriptan and other second generation 5-HT1D receptor agonists, have the ability to constrict porcine carotid arteriovenous anastomoses as well as the human isolated coronary artery. These two experimental models seem to serve as indicators, respectively, for the therapeutic and coronary side-effect potential of the compounds. Using these two models, we have now investigated the effects ofoxalate, a close analogue of sumatriptan. GMC2021 (30, 100, 300 and 1000 ~g • kg-1, i.v.) decreased the total carotid blood flow by exclusively decreasing arteriovenous anastomotic blood flow; capillary blood flow to the skin and ears was moderately increased. The mean + S.E.M. dose of GMC2021 eliciting a 50% decrease (EDso) in the porcine carotid arteriovenous anastomotic blood flow was found to be 1.1 + 0.3 I~mol. kg -I and the highest dose (1000 I~g" kg -1) produced a 67_ 4% reduction. The carotid haemodynamic effects of GMC2021 were reduced by the selective 5-HT1D receptor antagonist, GR127935 (N- 3% of contractions to 100 mM K+), GMC2021 was less potent in constricting the human isolated coronary artery (pD2:5.45 + 0.2; Emax: 21.0 + 4.8% of contractions to 100 mM K+). The above results suggest that GMC2021 constricts carotid arteriovenous anastomoses partly by a 5-HT1D receptor and partly by another, probably novel, receptor and that GMC2021 should be able to abort migraine headaches in patients, with perhaps a less propensity for coronary side effects.[

show abstract

Section: Systemic Haemodynamic Changessupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Investigations with GMC2021 in experimental models predictive of antimigraine activity and coronary side-effect potential

Saxena

Heiligers

VanDenBrink

et al. 1996

European Journal of Pharmacology

View full text Add to dashboard Cite

show abstract

“…Again, rats were injected with saline, agonist, or antagonist 4 h before killing. The doses of the serotonergic drugs used were determined based on the appropriate literature reports, specifically: 8-OH-DPAT, Owens et al (1990); sumatriptan, Mitsikostas et al (1996); GR 127935, Skingle et al (1996); DOI, Vaidya et al (1997); ketanserin, Semont et al (2000); RO 600175, Dekeyne et al (1999); SB 206553, Kennett et al (1996).…”

Section: Acute Treatments and Cell Proliferationmentioning

confidence: 99%

Serotonin-Induced Increases in Adult Cell Proliferation and Neurogenesis are Mediated Through Different and Common 5-HT Receptor Subtypes in the Dentate Gyrus and the Subventricular Zone

Banasr

Héry

Printemps

et al. 2003

Neuropsychopharmacol

472

319

View full text Add to dashboard Cite

Increase in serotonin (5-HT) transmission has profound antidepressant effects and has been associated with an increase in adult neurogenesis. The present study was aimed at screening the 5-HT receptor subtypes involved in the regulation of cell proliferation in the subgranular layer (SGL) of the dentate gyrus (DG) and the subventricular zone (SVZ) and to determine the long-term changes in adult neurogenesis. The 5-HT1A, 5-HT1B, and 5-HT2 receptor subtypes were chosen for their implication in depression and their location in/ or next to these regions. Using systemic administration of various agonists and antagonists, we show that the activation of 5-HT1A heteroreceptors produces similar increases in the number of bromodeoxyuridine-labeled cells in the SGL and the SVZ (about 50% over control), whereas 5-HT2A and 5-HT2C receptor subtypes are selectively involved in the regulation of cell proliferation in each of these regions. The activation of 5-HT2C receptors, largely expressed by the choroid plexus, produces a 56% increase in the SVZ, while blockade of 5-HT2A receptors produces a 63% decrease in the number of proliferating cells in the SGL. In addition to the influence of 5-HT1B autoreceptors on 5-HT terminals in the hippocampus and ventricles, 5-HT1B heteroreceptors also regulate cell proliferation in the SGL. These data indicate that multiple receptor subtypes mediate the potent, partly selective of each neurogenic zone, stimulatory action of 5-HT on adult brain cell proliferation. Furthermore, both acute and chronic administration of selective 5-HT1A and 5-HT2C receptor agonists produce consistent increases in the number of newly formed neurons in the DG and/or olfactory bulb, underscoring the beneficial effects of 5-HT on adult neurogenesis.

show abstract

“…However, the conclusions that the response to sumatriptan is mediated by 5-HT 1B receptor still seems valid, since both selective (SB224289, Gaster et al, 1998; as well as non-selective (GR127935, Skingle et al, 1996) 5-HT 1B receptor antagonists potently antagonized the carotid arteriovenous anastomotic constriction by sumatriptan (De Vries et al, 1996;1999b).…”

Section: Ligand Binding Properties Of Porcine 5-ht 1d Receptormentioning

confidence: 99%

Molecular cloning, sequence analysis and pharmacological properties of the porcine 5‐HT_1D receptor

Bhalla

Sharma

Wurch

et al. 2000

British J Pharmacology

View full text Add to dashboard Cite

show abstract

GR127935: a potent and selective 5-HT1D receptor antagonist

Cited by 187 publications

References 17 publications

Investigations with GMC2021 in experimental models predictive of antimigraine activity and coronary side-effect potential

Investigations with GMC2021 in experimental models predictive of antimigraine activity and coronary side-effect potential

Serotonin-Induced Increases in Adult Cell Proliferation and Neurogenesis are Mediated Through Different and Common 5-HT Receptor Subtypes in the Dentate Gyrus and the Subventricular Zone

Molecular cloning, sequence analysis and pharmacological properties of the porcine 5‐HT_1D receptor

Contact Info

Product

Resources

About

GR127935: a potent and selective 5-HT1D receptor antagonist

Cited by 187 publications

References 17 publications

Investigations with GMC2021 in experimental models predictive of antimigraine activity and coronary side-effect potential

Investigations with GMC2021 in experimental models predictive of antimigraine activity and coronary side-effect potential

Serotonin-Induced Increases in Adult Cell Proliferation and Neurogenesis are Mediated Through Different and Common 5-HT Receptor Subtypes in the Dentate Gyrus and the Subventricular Zone

Molecular cloning, sequence analysis and pharmacological properties of the porcine 5‐HT1D receptor

Contact Info

Product

Resources

About

Molecular cloning, sequence analysis and pharmacological properties of the porcine 5‐HT_1D receptor