New psychotherapeutic drugs.

Many new psychotherapeutic drugs are being developed for the major clinical indications for which they might be useful. As usual, we hope not only to obtain better drugs but also to posit hypotheses based on the presumed mode of action of effective drugs. Thus, we have a chance to test the role of serotonin, via the 5HT1A receptor, in anxiety or to test the possible significance of multiple benzodiazepine receptors. Among antidepressant agents, we have a chance to determine the relative roles of norpinephrine and serotonin in the pathogenesis of these disorders. We may also determine whether antidepressant actions involve a number of aminergic neurotransmitters. Among antipsychotic drugs, the importance of dopamine D2 receptor blockade has diminished with the advent of atypical drugs affecting a variety of other receptors. It might also be possible to delineate more clearly the role of serotonin in psychosis. The GABA hypothesis of mania can be tested in a number of ways by current drugs. The role of calcium antagonism remains to be demonstrated. The acetylcholine hypothesis of Alzheimer's disease will be tested further by new compounds under trial. However, it seems increasingly doubtful that current drugs under test will explicate the current hypothesis of the abnormal processing of beta-amyloid precursor protein in that disorder. Thus, we hope, as we have for the past three decades, to be able to use drugs not only to treat, but also to generate hypotheses. It is a kind of bootstrapping enterprise, but our ultimate hope is not only to be better able to treat our patients, but also to better understand their afflictions.