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Chemical structure of the agomelatine, the prototypical norepinephrine-dopamine disinhibitor.

Norepinephrine-dopamine disinhibitors (NDDIs) are a class of psychoactive drugs used as antidepressants and anxiolytics. They act by antagonizing the serotonin 5-HT2C receptor, which normally acts to inhibit norepinephrine and dopamine release, thereby promoting outflow of these neurotransmitters.

The only agent currently listed in this class is agomelatine. While NaSSAs and SARIs like mianserin, mirtazapine, trazodone, and nefazodone block 5-HT2C receptors as well, they also antagonize other receptors like 5-HT2A, 5-HT3, and/or α1-adrenergic, actions which run contradictorily to 5-HT2C blockade as saturation of these receptors inhibits norepinephrine and/or dopamine release.

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