Pharmacological Profile Reuptake Blockade

Early in the history of the tricyclic and tetracyclic antidepressants, the ability of these compounds to block the transporter site for norepinephrine was described (Axelrod et al. 1961) (see Table 12-1). The tertiary amines have greater affinity for the serotonin transporter, whereas the secondary amines are relatively more potent at the norepinephrine transporter. During the administration of amitriptyline, imipramine, or clomipramine, these tertiary amines are demethylated to secondary amines; thus, both serotonergic and noradrenergic effects occur. In addition, because dopamine is inactivated by norepinephrine transporters in the frontal cortex (Bymaster et al. 2002), norepinephrine reuptake inhibitors would be expected to increase dopamine concentrations in that region.

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