| Abstrakt: |
Although antidepressant drugs have been successfully used in the treatment of depression for more than two decades, the mechanism(s) by which these drugs produce their therapeutic effect is not understood. Tricyclic antidepressants have been shown to inhibit the neuronal uptake of norepinephrine (noradrenaline; NA) and serotonin, (5-hydroxytryptamine; 5-HT) (Glowinski and Axelrod, 1964) and their therapeutic effect has been related to this activity (Schildkraut, 1965). However, the effect of these drugs on the uptake of biogenic amines occurs immediately and does not correlate with the time course of the therapeutic response that usually sets in after only 1-3 wk of treatment. Moreover, there are other antidepressants, such as iprindole and mianserin, that do not block 5-HT and/or NA reuptake, but have been shown to lessen the symptoms of depression. Other drugs, such as cocaine, block the uptake of biogenic amines, but are not clinically effective antidepressants (Post et al., 1974). Some tricyclic antidepressants have also been shown to interact with the in vitro binding of specific radioactive ligands to several classes of neurotransmitter receptors in brain membrane preparations: (α-and γ-adrenergic (U'Prichard et al., 1978), serotonergic (Peroutka and Snyder, 1980), H1-histaminergic (Tran et al., 1981), and muscarinic cholinergic (Snyder and Yamamura, 1977) receptors. [ABSTRACT FROM AUTHOR] |
