Tricyclic Antidepressant Drug Interactions with Histamine and α-Adrenergic Receptors

Abstract

Tricyclic antidepressant drugs are remarkable in their therapeutic actions. When given acutely they are generally sedating. Then after a lag of 1-3 weeks, they alleviate depressive symptoms. Besides the delayed psychic energizing properties, the immediate apparent sedative actions may have importance for the relief of psychomotor agitation. This article describes influences of the drugs on histamine H1 and alpha-adrenergic receptors which may be of relevance to the energizing effects and relief of psychomotor agitation.

Evidence that mCPP may have behavioural effects mediated by central 5‐HT1C receptors

“…Although cyproheptadine and mianserin also have high affinity for histamine Hl-sites (Leysen et al, 1981) this explains neither the effects of metergoline which does not have high affinity for these sites (Leysen et al, 1981), nor the (less clear) effect of mesulergine (Closse, 1983). Furthermore, Hl-receptor antagonists themselves are sedative (Snyder, 1980). Another possibility is that the behavioural effects of mCPP under consideration are mediated by its affinity for a2-adrenoceptors (Smith & Suckow, 1985) as a2-adrenoceptor agonists such as clonidine cause sedation (Clineschmidt et al, 1979).…”

The potential therapeutic role of the enantiomers and metabolites of mianserin.

“…Desmethylmianserin is slightly less potent than mianserin as an inhibitor of noradrenaline uptake and antagonist at presynaptic ca-adrenoceptors, but is more active as a serotonin uptake blocker. The pattern of uptake inhibition is therefore in contrast to the tricyclic antidepressants, where the desmethyl derivatives, of, for example, amitriptyline or imipramine tend to, inhibit noradrenaline uptake more potently and serotonin uptake less potently than the parent antidepressants (Snyder, 1980). This difference is not due simply to the endocyclic nature of the methylamino moiety of mianserin, since a similar shift in favour of serotonin uptake inhibition follows demethylation of nortriptyline (Hyttel et al, 1980) and the Z-isomer of zimelidine (Ross & Renyi, 1977), both of which contain exocyclic methylamino moieties as found in amitriptyline and imipramine.…”

Second Messengers and Affective Illness

“…For instance, actions at alpha-adrenoceptors explain the differential activating and sedating effects of various tricyelic antidepressants. We noted a elose relationship between the ability oftricyelic antidepressants to reduce psychomotor agitation and their affinities for postsynaptic alphaI adrenoceptors in brain membranes (Snyder, 1980). The tertiary amine tricyelics, in general, are more potent than the secondary amines at these sites with doxepin and amitriptyline being particularly potent, about two times more active than imipramine.…”