[Predicted pharmacology of an antidepressant]

Pharmacological tests based on the reversal of effects induced by reserpine or reserpine-like drugs have been used extensively for the identification of potential antidepressants. The classical tests detect some of the antidepressants in addition to traditional tricyclics and monoamine oxydase inhibitors, but fail to identify other clinically effective antidepressants like mianserin and trazodone. New methods have therefore been developed including models based on reversal of various behavioural stereotypes of drug-induced effects. No single model is perfect, because all either detect drugs known not to be antidepressant (false positives) or, which is worse, fail to detect some clinically effective antidepressants (false negatives). The most reliable models involve reversal by antidepressants of the effects of bulbectomy in rats or selective suppression of REM sleep in cats, out neither is suitable for screening purposes. Neurochemical tests and receptor binding, like all tests for antidepressant activity, are fated to detect me-too drugs. Better and more relevant models must await a deeper understanding of the nature of depression.