Effects of alpha-adrenoceptor agonists and antagonists and of antidepressant drugs on pre- and postsynaptic alpha-adrenoceptors.

The effects of alpha-adrenoceptor agonists and antagonists and of antidepressant drugs were studied on pre- and postsynaptic alpha-adrenoceptors. The rat vas deferens, stimulated at low frequency (0.1 Hz) was used for presynaptic studies. The rat anococcygeus muscle was used in postsynaptic studies. In the agonist studies clonidine and guanfacine were selective for presynaptic alpha-adrenoceptors, methoxamine and phenylephrine were selective for postsynaptic alpha-adrenoceptors and noradrenaline and alpha-methylnoradrenaline were equipotent at pre- and post-synaptic alpha-adrenoceptors. In the antagonist studies piperoxane and yohimbine were selective for presynaptic alpha-adrenoceptors, phentolamine was equipotent at pre- and postsynaptic alpha-adrenoceptors and prazosin was a selective postsynaptic alpha-adrenoceptor antagonist. In the series of antidepressants studied, mianserin was the most potent antagonist at presynaptic alpha-adrenoceptors, followed by trazodone, amitriptyline and nortriptyline in descending order of potency. Mianserin was approximately two hundred times less potent than piperoxane as a presynaptic alpha-adrenoceptor antagonist. Viloxazine and desipramine were inactive. With the exception of viloxazine all of the antidepressants examined possessed postsynaptic alpha-adrenoceptor antagonist properties.