English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

GR127935 (N-[methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2 ,4-oxadiazol-3-yl) [1, 1-biphenyl]-4-carboxamide hydrochloride) has been recently introduced as an experimental tool to antagonize 5-HT(1B/D) receptor-mediated functional responses. The compound indeed exhibits a very high affinity and selectivity for 5-HT(1B/D) binding sites and it antagonizes a number of 5-HT(1B/D) receptor-mediated responses. The present experiments were performed to investigate the selectivity of GR127935 against functional responses mediated by 5-HT1-like, 'orphan' 5-HT1-like (5-ht7?), 5-HT2, 5-HT3 or 5-HT4 receptors in several in vivo preparations. Intravenous (i.v.) treatment with GR127935 (300 microg x kg(-1)) potently antagonized decreases in total carotid blood flow as well as hypotensive responses induced by the 5-HT1-like receptor agonist sumatriptan in rabbits. I.v. bolus injections of GR127935 (up to 500 and/or 1500 microg x kg(-1)) did not significantly modify 5-HT-induced: (i) tachycardia in the pig (5-HT4 receptor-mediated) and cat ('orphan' 5-HT1-like or, perhaps, 5-ht7 receptor-mediated); (ii) depressor effects in the rat and cat ('orphan' 5-HT1-like or 5-ht7 receptor-mediated); (iii) von Bezold-Jarisch reflex in the rat or the early phase of the urinary bladder contraction in the cat (both 5-HT3 receptor-mediated). In contrast, high doses (500-1500 microg x kg(-1)) of GR127935 suppressed 5-HT-induced pressor responses in the rat and cat and urinary bladder contractions (secondary phase) in the cat as well as the DOI ((+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride)-induced pressor responses in the rat, which are all mediated by 5-HT2A receptors. In conclusion, the present study demonstrates that GR127935 is a selective 5-HT(1B/D) receptor antagonist devoid of interactions at 'orphan' 5-HT1-like (5-ht7?), 5-HT3 and 5-HT4 receptors. However, GR127935 possesses a moderate 5-HT2A receptor blocking property, which is consistent with its binding profile (pKi: 7.4). Lastly, in view of the potent antagonist action of GR127935, the sumatriptan-induced hypotension in rabbits seems to be mediated by 5-HT(1B/D) receptors.

Interactions of GR127935, a 5-HT1B/D receptor ligand, with functional 5-HT receptors