THE FUTURE OF ANTIDEPRESSANTS

A common action of many antidepressants is the inhibition of the reupt ake of the biogenic amines norepinephrine, serotonin (5-HT) and/or dop amine into nerve terminals. Another postulated mechanism of action for many antidepressants is the downregulation of beta-adrenergic recepto rs postsynaptically after chronic administration. Many antidepressants have been reported to produce changes in the regulation of 5-HT1 and 5-HT2 receptors chronically. None of these mechanisms is completely sa tisfactory as a common antidepressant mechanism of action. Is it possi ble to unify these hypotheses of antidepressant action? A number of re ceptor changes have been recognized in depression. Usually, these impl icated receptors are linked to a G protein. Thus, it could be hypothes ized that depression may be the result of a disorder of the large fami ly of receptor-linked G proteins. Depression, a disorder in which ther e seems to be an important genetic component, could be expressed in ei ther the receptor or in the G proteins, leading to a defective linkage between the receptor and the G protein, resulting in abnormal transdu ction mechanisms. The concept of antidepressants is changing rapidly a s these agents appear with new therapeutic indications other than depr ession, such as panic disorder, obsessive compulsive disorder, etc. It can be expected that the presently available antidepressants might ev entually be considered anxiolytics or that benzodiazepines and 5-HTlA agonists could come to be viewed as disinhibiting substances.