Studies on the stereoselective effects of a novel 5-HT2 receptor antagonist on contractile responses of rat aorta

✍ Scribed by Erich O. Mikkelsen; Tove J. Nielsen; Niels C. B. Nyborg

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 309 KB
• Volume: 2
• Category: Article
• ISSN: 0899-0042
• DOI: 10.1002/chir.530020406

✦ Synopsis

The effect of the enantiomers of a novel 5-HT2 receptor antagonist, (~)-(1R,3S)-1- [2-[4-[3-(p-fluorophenyl)-l-indanyll-piperazinyllethyll-2imidazolidinone, was studied on serotonin (5-HT), noradrenaline (NA), potassium (K+), and calcium (Ca2+)-induced contractions in isolated rat thoracic aorta. The enantiomers shifted the 5-HT, NA, K + , and Ca2+ concentration-response curves to the right in a concentration-dependent manner and depressed the maximal contractile responses. The ( + )-enantiomer was a far more potent inhibitor of 5-HT-induced contractions than the ( -)-enantiomer. The ( + benantiomer and phentolamine, both at M, had equal inhibitory effects on NA-evoked contractions.

The ( + )-enantiomer was again more potent in inhibiting NA-induced contractions than the ( -)-enantiomer. Both enantiomers had an equieffective inhibitory effect on K + and Ca2+-induced contractions. The results show that the 5-HT and a-adrenoceptor antagonism of the two enantiomers is stereoselective, the ( + )-enantiomer being more potent than the ( -1-enantiomer. In contrast the enantiomers had equal, nonstereoselective inhibitory effects on K + and Ca2 + -evoked contractions.