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'{{Advert|date=June 2012}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 456689148 | IUPAC_name = ''(RS'')-4-amino-''N''-[(1-ethylpyrrolidin-2-yl)methyl]-<BR>5-ethylsulfonyl-2-methoxy-benzamide | image = Amisulpride2D1.svg | width = 250 | image2 = Amisulpride3Dan4.gif | width2 = 300 <!--Clinical data--> | tradename = | Drugs.com = {{drugs.com|international|amisulpride}} | pregnancy_AU = C| legal_status = Rx-only | routes_of_administration = Oral, [[Intramuscular injection|intramuscular]] <!--Pharmacokinetic data--> | bioavailability = 48%<ref name=Rosenzweig>{{ cite journal | author = Rosenzweig, P.; Canal, M.; Patat, A.; Bergougnan, L.; Zieleniuk, I.; Bianchetti, G. | title = A review of the pharmacokinetics, tolerability and pharmacodynamics of amisulpride in healthy volunteers. | journal = Human Psychopharmacology | volume = 17 | issue = 1 | year = 2002 | pages = 1–13 | pmid = 12404702 | doi = 10.1002/hup.320 }}</ref> | metabolism = ? | elimination_half-life = 12 h<ref name=Rosenzweig/> | excretion = [[Kidney|Renal]]<ref name=Rosenzweig/> <!--Identifiers--> | CAS_number_Ref = {{cascite|changed|??}} | CAS_number = 71675-85-9 | CAS_supplemental = | ATC_prefix = N05 | ATC_suffix = AL05 | PubChem = 2159 | IUPHAR_ligand = 963 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB06288 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 2074 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 8110R61I4U | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D07310 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 243712 <!--Chemical data--> | C=17 | H=27 | N=3 | O=4 | S=1 | molecular_weight = 369.48 g/mol | smiles = O=S(=O)(c1cc(c(OC)cc1N)C(=O)NCC2N(CC)CCC2)CC | InChI = 1/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) | InChIKey = NTJOBXMMWNYJFB-UHFFFAOYAK | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 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) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = NTJOBXMMWNYJFB-UHFFFAOYSA-N |legal_AU=S4}} '''Amisulpride''' (sold as '''Solian''', '''Sulpitac''', '''Amival''', '''Soltus''' or '''Amazeo'''), is an [[atypical antipsychotic]] used to treat [[psychosis]] in [[schizophrenia]] and episodes of [[mania]] in [[bipolar disorder]]. In the treatment of schizophrenia it appears to have comparable efficacy to [[olanzapine]].<ref>Komossa K, Rummel-Kluge C, Hunger H, Schmid F, Schwarz S, Silveira da Mota Neto JI, et al. Amisulpride versus other atypical antipsychotics for schizophrenia. Cochrane Database of Systematic Reviews [Internet]. John Wiley & Sons, Ltd; 2010 [cited 2013 Jul 24]. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006624.pub2/pdf </ref><ref>Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet [Internet]. 2009 Jan [cited 2013 Jul 24];373(9657):31–41. Available from: http://www.sciencedirect.com/science/article/pii/S014067360861764X </ref> In small doses it is also used to treat [[dysthymia]] where it appears to be at least as effective as conventional [[antidepressants]] according to a recent Cochrane review.<ref>Komossa K, Depping AM, Gaudchau A, Kissling W, Leucht S. Second-generation antipsychotics for major depressive disorder and dysthymia. Cochrane Database of Systematic Reviews [Internet]. John Wiley & Sons, Ltd; 2010 [cited 2013 Jul 24]. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008121.pub2/pdf</ref> It was introduced by [[Sanofi-Aventis]] in the 1990s. ==Approval Status== Amisulpride is not approved for use in the United States. It is also not approved by [[European Medicines Agency]]. It is approved in [[India]]. ==Pharmacology== Amisulpride function primarily as a [[D2 receptor|D₂]] and [[D3 receptor|D₃ receptor]] [[Receptor antagonist|antagonist]]. It has high affinity for these receptors with [[dissociation constant]]s of 2.2 nM and 2.4 nM, respectively. Although standard doses in the 400 to 1200&nbsp;mg a day range used to treat [[psychosis]] inhibit [[dopaminergic]] [[neurotransmission]], low doses in the 50 to 200&nbsp;mg range preferentially block inhibitory [[pre-synaptic]] [[autoreceptor]]s. This results in a facilitation of dopamine activity, and for this reason, low dose amisulpride has also been used to treat [[dysthymia]]. Amisulpride and its relative [[sulpiride]] have been shown to bind to and activate the [[GHB receptor]] at doses that are used for therapeutic purposes.<ref>{{ cite journal | author = Maitre, M.; Ratomponirina, C.; Gobaille, S.; Hodé, Y.; Hechler, V. | title = Displacement of [3H] gamma-hydroxybutyrate binding by benzamide neuroleptics and prochlorperazine but not by other antipsychotics | journal = European Journal of Pharmacology | volume = 256 | issue = 2 | pages = 211–214 | year = 1994 | month = Apr | pmid = 7914168 | doi = 10.1016/0014-2999(94)90248-8 }}</ref> Another recent study<ref>{{ cite journal | author = Nuss, P.; Hummer, M.; Tessier, C. | title = The use of amisulpride in the treatment of acute psychosis | journal = Therapeutics and Clinical Risk Management | volume = 3 | issue = 1 | year = 2007 | pages = 3–11 | pmid = 18360610 | pmc = 1936283 }}</ref> concludes that amisulpride is an appropriate first-line treatment for the management of acute psychosis. Though it has long been widely assumed that dopaminergic modulation is solely responsible for the respective [[antidepressant]] and [[antipsychotic]] properties of amisulpride, it has recently been shown that it also acts as a potent antagonist at the [[5-HT7 receptor|5-HT₇ receptor]].<ref name="pmid19337725">{{ cite journal | author = Abbas, A. I.; Hedlund, P. B.; Huang, X. P.; Tran, T. B.; Meltzer, H. Y.; Roth, B. L. | title = Amisulpride is a potent 5-HT7 antagonist: relevance for antidepressant actions in vivo | journal = Psychopharmacology | year = 2009 | pmid = 19337725 | volume = 205 | issue = 1 | pages = 119–128 | doi = 10.1007/s00213-009-1521-8 | pmc = 2821721 }}</ref> 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 amisulpride, a study prepared 5-HT₇ receptor knockout mice.<ref name="pmid19337725"/> 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 amisulpride.<ref name="pmid19337725"/> These results indicate that 5-HT₇ receptor antagonism plays a major role in the antidepressant effects of amisulpride.<ref name="pmid19337725"/> === Table 1: Pharmacologic Profile of Amisulpride (averaged K_i values taken from cloned human tissues) === {| class="wikitable sortable" |- ! Molecular target !! Binding Affinity (K_i in nM)<ref>{{cite web|last=National Institute of Mental Health|title=PDSP Ki Database|url=http://pdsp.med.unc.edu/pdsp.php|publisher=University of North Carolina|accessdate=5 July 2013}}</ref> |- | [[Serotonin transporter|SERT]] || >10000 |- | [[Norepinephrine transporter|NET]] || >10000 |- | [[Dopamine transporter|DAT]] || >10000 |- | [[5-HT1A receptor|5-HT_1A]] || >10000 |- | [[5-HT1B receptor|5-HT_1B]] || 1744 |- | [[5-HT1D receptor|5-HT_1D]] || 1341 |- | [[5-HT1E receptor|5-HT_1E]] || >10000 |- | [[5-HT2A receptor|5-HT_2A]] || 8304 |- | [[5-HT2B receptor|5-HT_2B]] || 13 |- | [[5-HT2C receptor|5-HT_2C]] || >10000 |- | [[5-HT3 receptor|5-HT₃]] || >10000 |- | [[5-HT5A receptor|5-HT_5A]] || >10000 |- | [[5-HT6 receptor|5-HT₆]] || 4154 |- | [[5-HT7 receptor|5-HT₇]] || 73.5 |- | [[Alpha-1A adrenergic receptor|α_1A]] || >10000 |- | [[Alpha-1B adrenergic receptor|α_1B]] || >10000 |- | [[Alpha-1D adrenergic receptor|α_1D]] || >10000 |- | [[Alpha-2A adrenergic receptor|α_2A]] || 1114 |- | [[Alpha-2C adrenergic receptor|α_2C]] || 1540 |- | [[Beta-1 adrenergic receptor|β₁]] || >10000 |- | [[Beta-2 adrenergic receptor|β₂]] || >10000 |- | [[Beta-3 adrenergic receptor|β₃]] || >10000 |- | [[M1 receptor|M₁]] || >10000 |- | [[M2 receptor|M₂]] || >10000 |- | [[M3 receptor|M₃]] || >10000 |- | [[M4 receptor|M₄]] || >10000 |- | [[M5 receptor|M₅]] || >10000 |- | [[D1 receptor|D₁]] || >10000 |- | [[D2 receptor|D₂]] || 2.2 |- | [[D3 receptor|D₃]] || 2.4 |- | [[D4 receptor|D₄]] || 2370 |- | [[D5 receptor|D₅]] || >10000 |- | [[H1 receptor|H₁]] || >10000 |- | [[H2 receptor|H₂]] || >10000 |- | [[H4 receptor|H₄]] || >10000 |- | [[Delta opioid receptor|δ opioid]] || >10000 |- | [[Kappa opioid receptor|κ opioid]] || >10000 |- | [[Mu receptor|μ opioid]] || >10000 |- | Prostaglandin E3 receptor || >10000 |- | Prostaglandin E4 receptor || >10000 |} ==Availability== Amisulpride is not approved by the [[Food and Drug Administration]] for use in the [[United States]], but it is used in Europe ([[France]], [[Germany]], [[Italy]], [[Switzerland]], [[Russia]], [[United Kingdom]], etc.), [[Israel]], [[India]], [[New Zealand]] and [[Australia]] to treat [[psychosis]] and [[schizophrenia]].<ref>{{ cite journal | author = Lecrubier, Y. ''et al.'' | title = Consensus on the Practical Use of Amisulpride, an Atypical Antipsychotic, in the Treatment of Schizophrenia | journal = Neuropsychobiology | volume = 44 | pages = 41–46 | year = 2001 | doi = 10.1159/000054913 | pmid = 11408792 | issue = 1 }}</ref><ref>{{ cite journal | author = Kaplan, A. | title = Psychotropic Medications Around the World | journal = Psychiatric Times | volume = 21 | issue = 5 | year = 2004 | url = http://www.psychiatrictimes.com/showArticle.jhtml?articleID=175802519 }}</ref> In Italy, in 50&nbsp;mg doses, it is also used as a treatment for [[dysthymia]]. ==Efficacy as an antidepressant== As an antidepressant, amisulpride is significantly more effective than: *[[Sertraline]] ([[Zoloft]])<ref>{{ cite pmid | 11712619 }}</ref> *[[Imipramine]] ([[Tofranil]])<ref>{{ cite pmid | 10757253 }}</ref> and equal to: * [[Amitriptyline]] (Elavil, Endep)<ref>{{ cite pmid | 10512080 }}</ref> * [[Amineptine]]<ref>{{ cite pmid | 9892856 }}</ref> in the treatment of [[dysthymia]]. In another study, anxiety measured by HAM-A total mean score decreased significantly more with amisulpride 50&nbsp;mg/day (63%) than with [[fluoxetine]] (Prozac) 20&nbsp;mg/day (54%; P&thinsp;=&thinsp;0.021).<ref>{{ cite journal | author = Smeraldi, E. | title = Amisulpride versus fluoxetine in patients with dysthymia or major depression in partial remission: a double-blind, comparative study | journal = Journal of Affective Disorders | volume = 48 | issue = 1 | pages = 47–56 | year = 1998 | pmid = 9495601 | doi = 10.1016/S0165-0327(97)00139-0 }}</ref> ==Side effects== [[Prolactin]] induction, thereby causing [[amenorrhoea]] and [[galactorrhoea]] in women, [[nausea]], [[weight gain]], [[insomnia]], [[akathisia]], [[sexual dysfunction]] although much less than similar drugs in its class, and less commonly [[QT interval]] prolongation (which can lead to serious heart [[arrhythmia]]s). Overdoses of amisulpride have been linked with [[torsades de pointes]].<ref>{{ cite journal | author = Isbister, G.; Murray, L.; John, S.; Hackett, L.; Haider, T.; O'Mullane, P.; Gosselin, S.; Daly, F. | title = Amisulpride deliberate self-poisoning causing severe cardiac toxicity including QT prolongation and torsades de pointes | journal = Medical Journal of Australia | volume = 184 | issue = 7 | pages = 354–356 | year = 2006 | pmid = 16584372 | url = http://www.mja.com.au/public/issues/184_07_030406/isbister10786_fm.html }}</ref> [[Tardive dyskinesia]], reported as possible side effect. ==Relative frequency of the more common side effects== More than one in ten people taking Amisulpride experience [[extrapyramidal symptoms]], including tremor, rigidity, [[hypokinesia]], [[hypersalivation]], [[akathisia]] and [[dyskinesia]]. Common side effects (more than one in one hundred people taking the drug) include weight gain, insomnia, anxiety, agitation, [[orgasmic dysfunction]], [[acute dystonia]], [[bradycardia]], [[hypotension]], constipation, nausea, vomiting, and dry mouth.<ref>{{ cite journal | author = Sandoz Limited | title = Amisulpride 100 mg Tablets Summary of Product Characteristics | year = 2012 | url = http://www.medicines.org.uk/emc/medicine/25318 }}</ref> ==References== {{Reflist}} {{Antipsychotics}} {{Antidepressants}} {{Dopaminergics}} {{GHBergics}} {{Serotonergics}} [[Category:Atypical antipsychotics]] [[Category:Benzamides]] [[Category:Pyrrolidines]] [[Category:Phenol ethers]] [[Category:Sulfones]] [[Category:Anilines]]'