EFFECTS OF THE ATYPICAL ANTIDEPRESSANT TRIMIPRAMINE ON FIELD POTENTIALS IN THE LOW MG2-MODEL IN GUINEA-PIG HIPPOCAMPAL SLICES()

Trimipramine has been classified as an atypical tricyclic antidepressa nt, because only weak inhibitory effects on serotonin and/or noradrena line reuptake have been found. Since some antidepressive drugs (e.g. i mipramine) and other agents used in the treatment of affective disorde rs (e.g. carbamazepine) modulate neuronal calcium channels, trimiprami ne was tested on field potential changes (fp) in the low Mg2+-model of epilepsy which has been shown to be affected by calcium antagonists. Trimipramine reduced the frequency of occurrence of fp in a dose depen dent manner (5-100 mu M). The threshold concentration of trimipramine which did not decrease the firing rate was approximately 1 mu M Simult aneous application of subthreshold concentrations (2 mu M) of the orga nic calcium antagonist verapamil with trimipramine decreased the firin g rate to 37.0 +/- 22.7% (means +/- SEM, n = 7) with respect to baseli ne values. In contrast, no additive effects of N-methyl-D-aspartate an tagonists and trimipramine were observed. In conclusion, the data sugg ests that the antidepressive effects observed with trimipramine treatm ent may be due to its inhibitory action on neuronal calcium channels. (C) 1998 Elsevier Science B.V./ECNP.