Drug Classification

As reviewed in Section 6.03.2, the majority of antidepressants in clinical use today act by enhancing the neurotransmission of monoamines, serotonin (5HT), NE, DA, or all three, either directly or indirectly.38 This is done by either blocking reuptake via monoamine transporters (Table 9) or blocking the metabolism of monoamines by inhibiting the major catalytic degradation enzymes, monoamine oxidase and catechol-O-methyltransferase (COMT). Other modes of action include direct or indirect modulation of receptors or signal transduction mechanism. Antidepressants that modulate neurotransmission of monoamine uptake inhibition are divided into those that are nonselective (e.g., TCAs, with dual action), SSRIs, and selective norepinephrine reuptake inhibitors (SNRIs). An additional class of antidepressant is the polypharmic heterocyclics acting at both reuptake sites and receptors. Other neuropeptide agents and transcription factors with potentially novel mechanisms of action, albeit acting through a final common monoaminergic pathway have been investigated.

Table 9 Antidepressants: inhibition of human serotonin (SERT), norepinephrine (NET) and dopamine (DAT) transportersĀ®

Generic name

Human SERT, Kd (nM)

Human NET, Ka (nM)

Human DAT, Kd (nM)

Selectivity SERT versus NET

Amitriptylins

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