항우울제의 약물역동

Pharmacokinetics of Antidepressants

The author has reviewed the literatures regarding the pharmacokinetics and pharmacodynamics of antidepressants, tricyclic antidepressants (TCA), monoamine oxidase inhibitors (MAOI) and other new antidepressants. Most interesting works in pharmacokinetics is the studies on the relationship between plasma level of drug and therapeutic outcome in some of TCA, suggesting the concept of the therapeutic window. But further study is needed to generalize this concept. The recent progress in studies on pharmacolo gical effects of TCA is the discovery that the antidepressant activities differ according to the chemical structure of the drugs and the expected mechanism of action on adrenergic or serotonergic activity of nervous system. But the fundamental mechanism of action is not known yet. And, though there are many explanation for antianxiety action, effects on sleep and EEG, antienuretic effect, and other behavioral effect and effects on psychoendocrinological system, they are not still integrated into a consistent mechanism. Even anticholinergic and antihistaminic effect other than adrenergic or serotonergic effect, which once has been known as the causes of side effects, are considered as a possible mechanism of psychotropic activity Reviewing the studies on mode of action and on mechanism of delayed onsst of clinical effects and lack of inhibition of amine uptake in some of new antidepressants, it can be stated that the emphasis has been moved from inhibition of amine uptake as the sole explanation, to effect on synthesis and turnover rate of amine neurotransmitters and, finally, to longer-term biochemical changes in pre- and/or post-synaptic receptor sensitivity and receptor sensitive cyclic AMP generating system, which are now suggested by some investigators as the common mode of action of TCA, MAOI and ECT. Therefore, the relative importance of noradrenergic or serotonergic system in the receptor sensitivity is still a matter for further experimentation. Finally, high a ffin ity imipramine binding site was found in rat brain and human platelets This use of receptor binding assays will yield as much useful information as it has in the case of opiates. In conclusion, it can be stated that the pharmacological activities of TCA are not simple and there are many contradiction among various proposed hypothesis for mode of action. Further studies will explain the final net effect of TCA. MAOIs have not been popular due to toxicity, but recent studies have indicated that some of new MAOI are quite effective, that specific therapeutic effect can be expected with some of new type of MAOI acting on A or B type MAO, and that side effects can be decreased by sele- cting one form of stereoisomer with potentiating clinically wanted effects.