amisulpride amisulpride amisulpride is an antiemetic and antipsychotic medication used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; and at higher doses by mouth to treat schizophrenia and acute psychotic episodes. it is sold under the brand names barhemsys (as an antiemetic) and solian, socian, deniban and others (as an antipsychotic). at very low doses it is also used to treat dysthymia. amisulprideclinical datatrade namessolian, barhemsys, othersother namesapd421ahfs/drugs.commonographlicense data us dailymed: amisulpride us fda: barhemsys pregnancycategory au: c routes ofadministrationby mouth, intravenousatc coden05al05 (who) legal statuslegal status au: s4 (prescription only) uk: pom (prescription only) us: ℞-only pharmacokinetic databioavailability48%protein binding16%metabolismliver (minimal; most excreted unchanged)elimination half-life12 hoursexcretionkidney (23–46%), faecalidentifiers iupac name 4-amino-n--5-ethylsulfonyl-2-methoxybenzamide cas number71675-85-9 npubchem cid2159iuphar/bps963drugbankdb06288 ychemspider2074 yunii8110r61i4ukeggd07310 ychebichebi:64045 nchemblchembl243712 ycomptox dashboard (epa)dtxsid5042613 echa infocard100.068.916 chemical and physical dataformulac17h27n3o4smolar mass369.48 g·mol−13d model (jsmol)interactive image smiles o=s(=o)(c1cc(c(oc)cc1n)c(=o)ncc2n(cc)ccc2)cc inchi inchi=1s/c17h27n3o4s/c1-4-20-8-6-7-12(20)11-19-17(21)13-9-16(25(22,23)5-2)14(18)10-15(13)24-3/h9-10,12h,4-8,11,18h2,1-3h3,(h,19,21) ykey:ntjobxmmwnyjfb-uhfffaoysa-n y ny (what is this?) (verify) it is usually classed with the atypical antipsychotics. chemically it is a benzamide and like other benzamide antipsychotics, such as sulpiride, it is associated with a high risk of elevating blood levels of the lactation hormone, prolactin (thereby potentially causing the absence of the menstrual cycle, breast enlargement, even in males, breast milk secretion not related to breastfeeding, impaired fertility, impotence, breast pain, etc.), and a low risk, relative to the typical antipsychotics, of causing movement disorders. amisulpride is indicated for use in the united states in adults for the prevention of postoperative nausea and vomiting (ponv), either alone or in combination with an antiemetic of a different class; and to treat ponv in those who have received antiemetic prophylaxis with an agent of a different class or have not received prophylaxis. amisulpride is believed to work by blocking, or antagonizing, the dopamine d2 receptor, reducing its signalling. the effectiveness of amisulpride in treating dysthymia and the negative symptoms of schizophrenia is believed to stem from its blockade of the presynaptic dopamine d2 receptors. these presynaptic receptors regulate the release of dopamine into the synapse, so by blocking them amisulpride increases dopamine concentrations in the synapse. this increased dopamine concentration is theorized to act on dopamine d1 receptors to relieve depressive symptoms (in dysthymia) and the negative symptoms of schizophrenia. it was introduced by sanofi-aventis in the 1990s. its patent expired by 2008, and generic formulations became available. it is marketed in all english-speaking countries except for canada. a new york city based company, lb pharmaceuticals, has announced the ongoing development of lb-102, also known as n-methyl amisulpride, an antipsychotic specifically targeting the united states. a poster presentation at european neuropsychopharmacology seems to suggest that this version of amisulpride, known as lb-102 displays the same binding to d2, d3 and 5ht7 that amisulpride does. medical uses 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. postoperative nausea and vomiting amisulpride is indicated for use in the united states in adults for the prevention of postoperative nausea and vomiting (ponv), either alone or in combination with an antiemetic of a different class; and to treat ponv in those who have received antiemetic prophylaxis with an agent of a different class or have not received prophylaxis. 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 very common (≥10% incidence) extrapyramidal side effects (eps; including dystonia, tremor, akathisia, parkinsonism). common (≥1%, <10% incidence) insomnia 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) anticholinergic side effects (although it does not bind to the muscarinic acetylcholine receptors and hence these side effects are usually quite mild) such as - constipation - dry mouth - disorder of accommodation - blurred vision rare (<1% incidence) hyponatraemia bradycardia hypotension palpitations urticaria seizures mania oculogyric crisis tardive dyskinesia blood dyscrasias such as leucopenia, neutropenia and agranulocytosis qt interval prolongation (in a recent meta-analysis of the safety and efficacy of 15 antipsychotic drugs amisulpride was found to have the 2nd highest effect size for causing qt interval prolongation) 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. 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