Search

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.

The possibility of a functional interdependence between central GABAA receptors and beta 2-adrenoceptors has been investigated using the ability of both types of agonist to potentiate the tic (head-twitch) response to 5-methoxy-N,N-dimethyltryptamine in the mouse. At a dose which selectively antagonised beta 1- but not beta 2-adrenoceptors, ICI 118,551 abolished the effects of single doses of muscimol, diazepam and pentobarbitone. Conversely, bicuculline abolished the potentiation caused by the beta 2-adrenoceptor agonist procaterol. Thus there is preliminary evidence that these two receptor types do show mutual interdependence.

The ability of beta-adrenoceptor agonists to potentiate the head-twitch response to 5-hydroxytryptophan (5-HTP) in mice was used to assess the in vivo sensitivity of beta-adrenoceptors 48 h after cessation of acute or chronic administration of desmethylimipramine (DMI) or iprindole (IPD). Neither acute nor chronic antidepressant administration significantly altered the head-twitch response to 5-HTP alone. Forty-eight hours after withdrawal from chronic but not acute pretreatment with DMI or IPD the potentiating effects of dobutamine, prenalterol and salbutamol were significantly decreased. This is consistent with a reduction in beta-adrenoceptor density and suggests that the 'spare' beta-adrenoceptor pool is small enough for this to result in functional subsensitivity. Implications of these findings are discussed.