Evidence that the hypotensive effect of WAY 100635, a 5-HT1A receptor antagonist, is related to vascular alpha 1-adrenoceptor blockade in the adult rat.

1. The effect of WAY100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride), a 5-HT1A receptor antagonist, on cardiovascular function was studied. 2. The i.v. injection of WAY100635 dose-dependently decreased blood pressure in anaesthetized rats; while in pithed rats WAY100635 (1 mg kg(-1)) displaced the phenylephrine pressor effect. 3. WAY100635 antagonized phenylephrine-induced contraction in rabbit and rat aorta (pA2 of 6.88 and 7.93 and Schild slopes of -0.83 and -1.21, respectively); while in rat caudal artery pK(B) was 7.45 and the Schild slope of -0.56, suggesting a complex interaction in this vessel. 4. The results show that WAY100635 induced hypotension in the anaesthetized rat and suggest that this effect could be partially explained by antagonism of vascular alpha1-adrenoceptors.