Chemical structure of agomelatine (Valdoxan), the prototypical NDDI.<unk>  and<unk><unk> s (NDDIs) are a class of drugs which act at specific sites to disinhibit downstream<unk>  and<unk>  release in the brain. Agomelatine, an antidepressant which disinhibits<unk>  and<unk>  release in the frontal cortex by antagonizing 5-HT2C receptors, was the first drug to be described as an NDDI. While many other drugs also antagonize 5-HT2C receptors to some degree or another, they tend to be very non-specific in their actions, and as a result, the term "NDDI" has generally, though not always (for instance, fluoxetine has been called an NDDI in addition to SSRI due to its (weak) blockade of 5-HT2C), been reserved for describing newer, more selective agents in which disinhibition of<unk>  and<unk>  release is their primary mechanism of action. Another drug that has been referred to as an NDDI in the medical literature is flibanserin, which is approved as a treatment for hypoactive sexual desire disorder in premenopausal women. Flibanserin disinhibits<unk>  and<unk>  release in the prefrontal cortex by activating 5-HT1A receptors in this area. Aside from agomelatine, fluoxetine, and flibanserin, as of present, no other drugs have been described as NDDIs in the medical literature, despite the fact that many other existing drugs possess effects consistent with those of the definition of an NDDI. In any case, more drugs labeled specifically as NDDIs may be seen in the future.
Norepinephrine–dopamine disinhibitor
Dopamine agonist
Dopamine antagonist
Alpha-adrenergic agonist
GABA analogue
Serotonin–norepinephrine–dopamine releasing agent
Adrenergic release inhibitor
Beta-adrenergic agonist