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.