The antagonist actions of WAY-100135 and its enantiomers on 5-HT1A receptor-mediated hyperpolarization of the rat isolated superior cervical ganglion.
A grease-gap extracellular recording technique was used to detect 5-HT1A receptor-mediated hyperpolarizing responses to 5-hydroxytryptamine (5-HT) in the rat isolated superior cervical ganglion. In the presence of the novel 5-HT1A receptor antagonist, WAY-100135 [N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylpropan amide], the responses to 5-HT were antagonised in a competitive manner with a pA2 value of 7.2 (6.9-8.5) and Schild plot slope of 1.0 (0.4-1.6), n = 20. The antagonist activity was greater in the (+) than the (-)enantiomer of WAY-100135. The pA2 value of the (+)enantiomer was 7.5 (7.2-8.0), Schild plot slope 1.2 (0.8-1.6), n = 17. In contrast the (-)enantiomer had weak antagonist activity (pA2 6.3 +/- 0.25, n = 3). No agonist activity of WAY-100135 or its enantiomers were observed in this study.
Rhodes
K F
KF
Department of Biomedical Research, Wyeth Research Ltd., Maidenhead, Berkshire, UK.
Dover
G
G
Lattimer
N
N
D000818:Animals; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists; D013237:Stereoisomerism; D017783:Superior Cervical Ganglion / Q000187:drug effects*
D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C081293:WAY 100135; D012701:Serotonin