Cardiovascular actions of medetomidine and their reversal by atipamezole

The cardiovascular effects of medetomidine were evaluated in conscious spontaneously hypertensive (SH) rats, anaesthetized normotensive rats and cats, and in the cardiovascular system of the pithed rat. The drug proved to be a highly selective alpha 2-adrenoceptor agonist in the cardiovascular system of pithed rats so that both its pre and postsynaptic actions could be antagonized by atipamezole but not by prazosin. Medetomidine showed high stereoselectivity, the pharmacologically active enantiomer being dexmedetomidine. Medetomidine was bradycardic and, after an initial increase in blood pressure, hypotensive in anaesthetized and conscious rats and in anaesthetized cats. The mechanism is activation of alpha 2-adrenoceptors since atipamezole efficiently antagonized the hypotensive and bradycardic action of medetomidine in anaesthetized cats. Finally, it was observed that atropine was not efficient in antagonizing the medetomidine-induced bradycardic response in anaesthetized rats.