Pharmacodynamics +<unk>  Site Ki (nM) Species Ref >10,000 Human >10,000 Human >10,000 Human 5-HT1A >10,000 Human 5-HT1B 1,744 Human 5-HT1D 1,341 Human 5-HT1E >10,000 Human 5-HT2A 8,304 Human 5-HT2B 13 Human 5-HT2C >10,000 Human 5-HT3 >10,000 Human 5-HT5A >10,000 Human 5-HT6 4,154 Human 5-HT7 11.5 Human α1A >10,000 Human α1B >10,000 Human α1D >10,000 Human α2A 1,114 Human α2C 1,540 Human β1 >10,000 Human β2 >10,000 Human β3 >10,000 Human D1 >10,000 Human D2 3.0 Human D3 3.5 Rat D4 2,369 Human D5 >10,000 Human H1 >10,000 Human H2 >10,000 Human H4 >10,000 Human M1 >10,000 Human M2 >10,000 Human M3 >10,000 Human M4 >10,000 Human M5 >10,000 Human σ1 >10,000 Rat σ2 >10,000 Rat >10,000 Human >10,000 Human >10,000 Human 50 () Rat () >10,000 Rat Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.<unk>  functions primarily as a dopamine D2 and D3 receptor antagonist. It has high affinity for these receptors with dissociation constants of 3.0 and 3.5 nM, respectively. Although standard doses used to treat psychosis inhibit dopaminergic neurotransmission, low doses preferentially block inhibitory presynaptic autoreceptors. This results in a facilitation of dopamine activity, and for this reason, low-dose<unk>  has also been used to treat dysthymia.<unk>  and its relatives sulpiride, levosulpiride, and sultopride have been shown to bind to the high-affinity GHB receptor at concentrations that are therapeutically relevant ( = 50 nM for<unk> .<unk> , sultopride and sulpiride respectively present decreasing in vitro affinities for the D2 receptor (IC50 = 27, 120 and 181 nM) and the D3 receptor (IC50 = 3.6, 4.8 and 17.5 nM). Though it was long widely assumed that dopaminergic modulation is solely responsible for the respective antidepressant and antipsychotic properties of<unk> , it was subsequently found that the drug also acts as a potent antagonist of the serotonin 5-HT7 receptor (Ki = 11.5 nM). Several of the other atypical antipsychotics such as risperidone and ziprasidone are potent antagonists at the 5-HT7 receptor as well, and selective antagonists of the receptor show antidepressant properties themselves. To characterize the role of the 5-HT7 receptor in the antidepressant effects of<unk> , a study prepared 5-HT7 receptor knockout mice. The study found that in two widely used rodent models of depression, the tail suspension test, and the forced swim test, those mice did not exhibit an antidepressant response upon treatment with<unk> . These results suggest that 5-HT7 receptor antagonism mediates the antidepressant effects of<unk> .<unk>  also appears to bind with high affinity to the serotonin 5-HT2B receptor (Ki = 13 nM), where it acts as an antagonist. The clinical implications of this, if any, are unclear. In any case, there is no evidence that this action mediates any of the therapeutic effects of<unk> .<unk>  shows stereoselectivity in its actions. Aramisulpride ((R)-amisulpride) has higher affinity for the 5-HT7 receptor (Ki = 47 nM vs. 1,900 nM) while esamisulpride ((S)-amisulpride) has higher affinity for the D2 receptor (4.0 nM vs. 140 nM). An 85:15 ratio of aramisulpride to esamisulpride (SEP-4199) which provides more balanced 5-HT7 and D2 receptor antagonism than racemic<unk>  (50:50 ratio of enantiomers) is under development for the treatment of bipolar depression.
Amisulpride
Icatibant
Deutetrabenazine
Suvorexant
Adatanserin
Bedaquiline
Daridorexant
Pirlindole