Behavioural and neurochemical studies of the action of atypical antidepressants.

With a view to finding suitable methods for studying the antidepressive properties of the so-called atypical antidepressants we investigated the relationship between the affinity of these substances for the membrane lipids and their influence on the in vitro accumulation of neurotransmitters, on the radioligand binding and on some behavioural phenomena. The antidepressants tested were found to be localized in the region of the polar head group of the lipid membrane bilayer which serves as a recognition site for various ligands. Unlike the tricyclic antidepressants which inhibit the NA, DA and 5-HT uptake, the atypical antidepressants studied (azaphen, befuraline, pirlindol, inkazan) were less active and inhibited the uptake of only one or two monoamines. A highly significant correlation was also found between the influence of the drugs on the surface electric charge of the lipid membrane bilayer and the inhibition they produced of the neurotransmitter uptake. It was established that the atypical antidepressants studied were less active than the tricyclic antidepressants with respect to the displacement of labelled imipramine from the binding site, suggesting that this test is not very suitable for studying these drugs. With Porsolt's model of behavioural depression in mice all substances tested (tricyclic and atypical antidepressants) exhibited such an action (prevention of the behavioural depression). With the model of depression through escaping the learned helplessness (Anisman's test) in mice under acute conditions the antidepressants studied did not prevent the development of this state while in case of chronic treatment they prevented it.