Mechanism of Action

The precise molecular mechanism responsible for the antidepressant action of the TCA drugs is unknown, although a number of hypotheses have been generated. Many of these involve alterations in neurotransmission of norepinephrine or serotonin or both.

p-Adrenoceptor down-regulation at central nora-drenergic synapses is one popular theory used to explain the antidepressant properties of TCA drugs and other antidepressants. This theory focuses on a cascade of adaptive changes at the noradrenergic synapse that appears to be triggered by inhibition of norepinephrine neuronal reuptake by TCA drugs (Fig. 33.2). Subsensi-tivity in the p-adrenoceptor-coupled adenylyl cyclase system and associated reductions in p-adrenoceptor density appear to be common features of the antide-pressants and of electroconvulsant treatment. Moreover, the time-dependent changes in p-adrenoceptor

Inhibition of nerve terminal NE neuronal uptake system

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