Is Down-regulation of β-Adrenoceptors Necessary for Antidepressant Activity?

The majority of clinically effective antidepressant drugs are thought to induce, on the basis of in vitro neurochemical studies, an increase in the synaptic concentration of noradrenaline and/or serotonin by inhibiting either the metabolism or the neuronal reuptake of these neurotransmitters. Whereas this pharmacological effect is often assumed to be related to the therapeutic effects of these compounds and, indeed, is a commonly used indication of possible antidepressant activity, there exists a poor correlation between the time-course of clinical response to these drugs and their neurochemical effects (Sulser et al., 1978). Thus, despite an immediate manifestation of increased monoamine availability after acute administration, the therapeutic effects of these compounds are not usually seen until after 2 to 3 weeks of continual treatment. Additionally, so-called 'atypical' antidepressants such as mianserin and iprindole appear not to inhibit the metabolism or reuptake of monoamines (see Stone, 1983).