Nefazodone transporters

FIGURE 2.6 Serotonergic synapse. Serotonin binds to at least seven different receptors. The most relevant are the 5-HTi receptors (1), 5-HT2 receptors (2), and 5-HT3 receptors (3). Antagonists of the 5-HT2 receptor include nefazodone and the majority of atypical antipsychotic drugs. The serotonin transporter (4) pumps serotonin back into the serotonergic neuron, which can be blocked by drugs such as venlafaxine, clomipramine, imipramine, and amitriptyline. 

Rickels K, Schweizer E, Clary C, et al Nefazodone and imipramine in major depression a placebo-controlled trial. Br J Psychiatry 164 802-805, 1994 Riddell EG Studies on Li" transport using 7Li and 61i nuclear magnetic resonance, in Lithium and the Cell. Edited by Birch NJ. San Diego, CA, Academic Press, 1991, pp 85-98... 

Kostrubsky SE, Strom SC, Kalgutkar AS, et al. Inhibition of hepatobiliary transport as a predictive method for clinical hepatotoxicity of nefazodone. Toxicol Sci. 2006 90(2) 451-459. 

The MAO inhibitor tranylcypromine is amphetamine-like in structure but interacts only weakly at DA transporters. The phenylpiperazine nefazodone, and to a lesser extent, the structurally related trazodone have weak inhibitory actions on 5-HT transport nefazodone also may have a minor effect on NE transport. This agent also has a prominent direct antagonistic effect at S-HT receptors that may contribute to antidepressant and anxiolytic activity. Both drugs also may inhibit presynaptic 5-HTj subtype autoreceptors to enhance neuronal release of 5-HT, though they probably also exert at least partial-agonist effects on postsynaptic 5-HTj receptors. Trazodone also blocks cerebral and Hj receptors, possibly contributing to its tendency to induce priapism and sedation, respectively. 

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