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Studies on the stereoselective effects of a novel 5‐HT 2 receptor antagonist on contractile responses of rat aorta
Author(s) -
Mikkelsen Erich O.,
Nielsen Tove J.,
Nyborg Niels C. B.
Publication year - 1990
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530020406
Subject(s) - chemistry , enantiomer , antagonist , stereoselectivity , antagonism , stereochemistry , phentolamine , serotonin , receptor , pharmacology , biochemistry , medicine , catalysis
The effect of the enantiomers of a novel 5‐HT 2 receptor antagonist, (±)‐(1R,3S)‐1‐[2‐[4‐[3‐( p ‐fluorophenyl)‐1‐indanyl]‐piperazinyl]ethyl]–2‐imidazolidinone, was studied on serotonin (5‐HT), noradrenaline (NA), potassium (K + ), and calcium (Ca 2+ )‐induced contractions in isolated rat thoracic aorta. The enantiomers shifted the 5‐HT, NA, K + , and Ca 2+ 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 (+)‐enantiomer and phentolamine, both at 10 −6 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 Ca 2+ ‐induced contractions. The results show that the 5‐HT and α‐adrenoceptor antagonism of the two enantiomers is stereoselective, the (+)‐enantiomer being more potent than the (−)‐enantiomer. In contrast the enantiomers had equal, nonstereoselective inhibitory effects on K + and Ca 2+ ‐evoked contractions.