SEROTONIN SELECTIVE ANTIDEPRESSANT DRUGS - PAST, PRESENT, FUTURE

Classic antidepressant drugs, amine uptake inhibitors of the imipramin e type and the monoamine oxidase inhibitors, alter the functioning of serotonin (5-hydroxytryptamine, 5-HT) neurons in the brain. This disco very, made more than two decades ago, has had a profound impact on the study of depressive illness as well as on the development of new mode ls of antidepressant treatment. Apart from their obvious clinical valu e, antidepressant drugs have come to be used as research tools to stud y the pathophysiology of depressive illness. A main goal in the develo pment of antidepressant drugs has been to design drugs with more selec tive effects on the nerve cells that are thought to be important in de pressive illness, thereby avoiding unnecessary side effects and possib ly enhancing therapeutic effects. Drugs that selectively affect 5-HT n eurons have proved to be uptake inhibitors-including fluoxetine, fluvo xamine, paroxetine, sertraline, and citalopram-and are now available. All of them appear to have an antidepressant effect equivalent to stan dard reference compounds, with a different spectrum of side effects. O ne of the most interesting aspects of the serotonergic drugs is their broad spectrum of action, in particular, their effects in patients wit h obsessive-compulsive disorder, panic disorder, and possibly some dis orders of impulse control. There is still relatively little knowledge of which aspects of 5-HT function are important for the antidepressant , antiobsessive, and antipanic effects. The availability of drugs that selectively affect the different 5-HT receptors, such as the partial 5-HT1A agonist gepirone, will presumably be helpful for modern studies of the ''anatomy of melancholy.''