GR127935: a potent and selective 5-HT1D receptor antagonist

Behav Brain Res. 1996;73(1-2):157-61. doi: 10.1016/0166-4328(96)00089-7.


GR127935 is the most potent 5-HT1D receptor antagonist yet described, possessing nanomolar affinity at human 5-HT1D receptors. Sumatriptan-induced contractions of the dog isolated basilar artery and saphenous vein are antagonised by GR127935 in an insurmountable manner indicative of its slow dissociation from the 5-HT1D receptor. 5-HT1D receptor-mediated hypothermia and rotational behaviour in guinea-pigs are antagonised potently, and with long duration, by GR127935, administered by a variety of routes. GR127935 also blocks central 5-HT1D autoreceptors in vitro and in vivo. GR127935 has much lower affinity at other 5-HT, and non-5-HT, receptors. In functional studies, GR127935 fails to affect 5-HT2 receptor-mediated 'wet dog shakes' in guinea-pigs and 5-HT1A receptor-mediated inhibition of 5-HT release in rat dorsal raphé nucleus. The compound has a good safety profile in all species tested. It is concluded that GR127935 is a useful pharmacological tool to characterise 5-HT1D receptor function.

Publication types

  • Review

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Dogs
  • Guinea Pigs
  • Humans
  • Oxadiazoles / metabolism
  • Oxadiazoles / pharmacology*
  • Oxadiazoles / toxicity
  • Piperazines / metabolism
  • Piperazines / pharmacology*
  • Piperazines / toxicity
  • Rats
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / metabolism
  • Serotonin Antagonists / metabolism
  • Serotonin Antagonists / pharmacology*
  • Serotonin Antagonists / toxicity


  • Oxadiazoles
  • Piperazines
  • Receptors, Serotonin
  • Serotonin Antagonists
  • GR 127935