These results suggest that 5-HT7 receptor antagonism mediates the antidepressant effects of amisulpride.Amisulpride 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 amisulpride.Amisulpride 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 amisulpride (50:50 ratio of enantiomers) is under development for the treatment of bipolar depression. Society and culture
Brand names
Brand names include: Amazeo, Amipride (AU), Amival, Solian (AU, IE, RU, UK, ZA), Soltus, Sulpitac (IN), Sulprix (AU), Midora (RO) and Socian (BR). Availability
Amisulpride was not approved by the Food and Drug Administration for use in the United States until February 2020, but it is used in Europe, Israel, Mexico, India, New Zealand and Australia to treat psychosis and schizophrenia.An IV formulation of Amisulpride was approved for the treatment of postoperative nausea and vomiting ("PONV") in the United States in February 2020. History
The U.S. Food and Drug Administration (FDA) approved amisulpride based on evidence from four clinical trials of 2323 subjects undergoing surgery or experiencing nausea and vomiting after the surgery.
This means that to achieve the sufficient occupancy (~60–80%) of the central D2 receptors in order to elicit its therapeutic effects a dose must be given that is enough to saturate peripheral D2 receptors including those in the anterior pituitary. Somnolence. Discontinuation
The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly there may be a feeling of the world spinning, numbness, or muscle pains. Symptoms generally resolve after a short period of time.There is tentative evidence that discontinuation of antipsychotics can result in psychosis. It may also result in reoccurrence of the condition that is being treated. Rarely tardive dyskinesia can occur when the medication is stopped. Overdose
Torsades de pointes is common in overdose. Amisulpride is moderately dangerous in overdose (with the TCAs being very dangerous and the SSRIs being modestly dangerous). Interactions
Amisulpride should not be used in conjunction with drugs that prolong the QT interval (such as citalopram, bupropion, clozapine, tricyclic antidepressants, sertindole, ziprasidone, etc. ), reduce heart rate and those that can induce hypokalaemia. Likewise it is imprudent to combine antipsychotics due to the additive risk for tardive dyskinesia and neuroleptic malignant syndrome. Pharmacology
Pharmacodynamics
Amisulpride 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.