Inhibition of in vitro and ex vivo uptake of noradrenaline and 5-hydroxytryptamine by five antidepressants; correlation with reduction of spontaneous firing rate of central monoaminergic neurones.

The principal neurochemical property of tricyclic antidepressants is the blockade of noradrenaline (NA) and/or 5-hydroxytryptamine (5-HT) uptake into monoaminergic nerve endings. Electrophysiological studies show that these drugs also decrease the firing rate of the noradrenergic neurones of the locus coeruleus (L.C.) and of the serotonergic neurones of the dorsal raphe (D.R.). In order to assess the relation between the two phenomena, the influence of five tricyclic antidepressants on NA and 5-HT uptake was studied in vitro. The concentrations required to produce a 50% inhibition (IC50) were determined and correlated with the respective doses required to reduce to 50% (ID50) the firing rate of L.C. and D.R. neurones. Ex vivo experiments were also performed to study the influence of the tricyclic antidepressants on NA and 5-HT uptake when administered i.v. at the doses decreasing to 50% the firing rate of L.C. and D.R. cells. The inhibition of the NA uptake by tricyclic antidepressants can account, at least in part, for the inhibition of the firing rate of L.C. neurones observed after acute i.v. administration. In the case of serotonergic neurons, the results do not allow a firm conclusion.