Amisulpride

Schizophrenia Although according to other studies it appears to have comparable efficacy to olanzapine in the treatment of schizophrenia, amisulpride augmentation, similarly to sulpiride augmentation, has been considered a viable treatment option (although this is based on low-quality evidence) in clozapine-resistant cases of schizophrenia. Another recent study concluded that amisulpride is an appropriate first-line treatment for the management of acute psychosis. Depression Amisulpride is approved and used at low doses in the treatment of dysthymia and major depressive disorder. Whereas typical doses used in schizophrenia block postsynaptic dopamine D2-like receptors and reduce dopaminergic neurotransmission, low doses of amisulpride preferentially block presynaptic dopamine D2 and D3 autoreceptors and thereby disinhibit dopamine release and enhance dopaminergic neurotransmission. A 2010 Cochrane review found that low-dose amisulpride was effective in the treatment of dysthymia. Likewise, a 2024 literature review found that low-dose amisulpride was effective for dysthymia. The drug is approved for depression specifically in Italy, Greece, and certain other European countries. In the United States, it is available in the form of a 5mg/2mL (2.5mg/mL) solution for intravenous administration. ==Contraindications==

Amisulpride's use is contraindicated in the following disease states and populations • Pheochromocytoma • Concomitant prolactin-dependent tumours e.g. prolactinoma, breast cancer • Movement disorders (e.g. Parkinson's disease and dementia with Lewy bodies) • Lactation • Children before the onset of puberty Neither is it recommended to use amisulpride in patients with hypersensitivities to amisulpride or the excipients found in its dosage form. ==Adverse effects==

The adverse effect frequencies listed below are when prescribed as an antipsychotic, at much higher doses than are used to treat depression and nausea and vomiting. ;Very Common (≥10% incidence) • Insomnia • Somnolence • Hypersalivation • Nausea • Headache • Hyperactivity • Vomiting • Hyperprolactinaemia (which can lead to galactorrhoea, breast enlargement and tenderness, sexual dysfunction, etc.) • Weight gain (produces less weight gain than chlorpromazine, clozapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, zotepine and more (although not statistically significantly) weight gain than haloperidol, lurasidone, ziprasidone and approximately as much weight gain as aripiprazole and asenapine)) Hyperprolactinaemia results from antagonism of the D2 receptors located on the lactotrophic cells found in the anterior pituitary gland. Amisulpride has a high propensity for elevating plasma prolactin levels as a result of its poor blood–brain barrier penetrability and hence the resulting greater ratio of peripheral D2 occupancy to central D2 occupancy. 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. 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. 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.), as this can cause potential life threatening arrhythmias (Torsades de pointes, Ventricular tachycardia, and Ventricular fibrillation) ==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. Amisulpride, 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 amisulpride, it was subsequently found that the drug also acts as a potent antagonist of the serotonin 5-HT7 receptor (Ki = 11.5 nM). 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). Pharmacokinetics The oral bioavailability of amisulpride is 48%. Its plasma protein binding is 16%. The drug is metabolized by the liver but its metabolism is minimal. Its elimination half-life is 12hours. Amisulpride is eliminated in urine (23–46%) and feces and is excreted mostly unchanged. ==Chemistry==

Amisulpride is a benzamide derivative. It is structurally related to other benzamide dopamine receptor antagonists employed as antipsychotics and antiemetics including levosulpiride, metoclopramide, nemonapride, remoxipride, sulpiride, sultopride, tiapride, and veralipride. Chemically, it is also known as aminosultopride, differing from sultopride only in possessing an amino substituent on its benzene ring. ==History==

Amisulpride was introduced by Sanofi-Aventis in the 1990s. Its patent expired by 2008, and generic formulations became available. ==Society and culture==

Brand names Brand names include: Amazeo, Amipride (AU), Amival, Deniban, Solian (AU, IE, RU, UK, ZA), Soltus, Sulpitac (IN), Sulprix (AU), Midora (RO) and Socian (BR, PT). Availability Amisulpride is not approved by the Food and Drug Administration for use in the United States in psychiatric indications, but it is approved and in use throughout Europe, An IV formulation of Amisulpride was approved for the treatment of postoperative nausea and vomiting ("PONV") in the United States in February 2020. ==Research==

Bipolar depression SEP-4199 (non-racemic amisulpride), an 85:15 ratio of aramisulpride ((R)-amisulpride) to esamisulpride ((S)-amisulpride), which is theorized to provide more balanced serotonin 5-HT7 and dopamine D2 receptor antagonism than racemic amisulpride (a 50:50 ratio of its (R)- and (S)-enantiomers), is or was under development by Sunovion Pharmaceuticals for the treatment of bipolar depression in the United States and other countries. However, its development may have been discontinued. Chemical derivatives A more lipophilic and centrally permeable derivative of amisulpride, N-methylamisulpride (developmental code name LB-102), is under development by LB Pharmaceuticals for the treatment of schizophrenia in the United States and other countries. ==See also==