WAY 405, a new silent 5-HT (1A) receptor antagonist with low affinity for vascular alpha (1)-adrenoceptors.
1 The effect of WAY 405 ((R)-N-(2-methyl-(4-indolyl-1-piperazinyl)ethyl)-N-(2-pyridinyl) cyclohexane carboxamide), a putative 5-HT(1A) receptor antagonist, on cardiovascular function was studied. 2 In anaesthetized rats, the i.v. injection of WAY 405 did not significantly modify basal heart rate nor blood pressure at doses of 1, 3, 10 and 30 microg kg(-1); while the antagonist dose dependently antagonized the 5-HT(1A) receptor agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin)-induced hypotension and bradycardia. 3 WAY 405 antagonized noradrenaline-induced contraction in isolated arteries, with pK(B) values of 6.6+/-0.1, 6.5+/-0.1 and 6.5+/-0.1, for rat tail artery (alpha(1A)-adrenoceptors), rabbit aorta (alpha(1B)-adrenoceptors), and rat aorta (alpha(1D)-adrenoceptors) respectively. 4 The results show that in the control of blood pressure the new compound, WAY 405, behaves as a silent 5-HT(1A) receptor antagonist in the anaesthetized rat, also having low affinity for vascular alpha(1)-adrenoceptors.
Villalobos-Molina
R
R
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados-Sede Sur, México City.
Orozco-Méndez
M
M
López-Guerrero
J J
JJ
Gallardo-Ortíz
I A
IA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000037:antagonists & inhibitors; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013623:Tail / Q000098:blood supply; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000631:Aminopyridines; C514231:N-(2-methyl-(4-indolyl-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexane carboxamide; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014662:Vasoconstrictor Agents; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D009638:Norepinephrine