Behavioural and neurochemical studies of the action of atypical antidepressants
Valdman, A.V.; Avdulov, N.A.; Rozganets, V.V.; Rusacov, D.Y.
Acta Physiologica et Pharmacologica Bulgarica 9(3): 3-10
1983
ISSN/ISBN: 0323-9950 PMID: 6142583 Document Number: 209702
With a view to finding suitable methods for studying the antidepressive properties of the so-called atypical antidepressants, 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 behavioral phenomena were investigated. The antidepressants tested were 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 uptake, the atypical antidepressants studied (azaphen, befuraline, pirlindol and inkazan) were less active and inhibited the uptake of only 1 or 2 monoamines. A highly significant correlation was also found between the influence of the drugs of the surface electric charge of the lipid membrane bilayer and the imhibition they produced of the neurotransmitter uptake. The atypical antidepressants studied were evidently less active than the tricyclic antidepressants with respect to the displacement of labeled imipramine from the binding site, suggesting that this test was not very suitable for studying these drugs. With Porsolt's model of behavioral depression in mice, all substances tested (tricyclic and atypical antidepressants) exhibited such an action (prevention of the behavioral 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 the case of chronic treatment they prevented it.