Amisulpride, sold under the brand name Solian among others, is an antipsychotic medication used to treat schizophrenia.[1] It is also used to treat dysthymia.[5] 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.[6][7][8] It has also been found to be modestly more effective in treating schizophrenia than the typical antipsychotics.[7] Amisulpride is believed to work by reducing signalling via the dopamine D2 receptor. In amisulpride's case this is by blocking, or antagonizing, the receptor. Amisulpride's effectiveness 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.[5] It was introduced by Sanofi-Aventis in the 1990s. Its patent had expired by 2008 and hence generic formulations are now available.[9] It is marketed in all English-speaking countries except for Canada and the United States.[8] In a 2013 study in a comparison of 15 antipsychotic drugs in effectiveness in treating schizophrenic symptoms, amisulpride was ranked second and demonstrated high effectiveness. 11% more effective than olanzapine (3rd), 32-35% more effective than haloperidol, quetiapine, and aripiprazole, and 25% less effective than clozapine (1st).[7] Although according to other studies it appears to have comparable efficacy to olanzapine in the treatment of schizophrenia.[10][11] 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.[12][13] Another recent study concluded that amisulpride is an appropriate first-line treatment for the management of acute psychosis.[14] Amisulpride's use is contraindicated in the following disease states[1][15][6] Neither is it recommended to use amisulpride in patients with hypersensitivities to amisulpride or the excipients found in its dosage form.[1] 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%[18]) 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.[19][20] Torsades de pointes is common in overdose.[21][22] Amisulpride is moderately dangerous in overdose (with the TCAs being very dangerous and the SSRIs being modestly dangerous).[23][24] Amisulpride should not be used in conjunction with drugs that prolong the QT interval (such as citalopram, venlafaxine, bupropion, clozapine, tricyclic antidepressants, sertindole, ziprasidone, etc.),[23] 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.[23] 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.[26] 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 amisulpride has also been used to treat dysthymia.[1] Amisulpride and its relatives sulpiride, levosulpiride, and sultopride have been shown to bind to the high-affinity GHB receptor at concentrations that are therapeutically relevant (IC50 = 50 nM for amisulpride).[27] 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).[29] 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).[26] 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.[26] 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.[26] These results suggest that 5-HT7 receptor antagonism mediates the antidepressant effects of amisulpride.[26] Amisulpride also appears to bind with high affinity to the serotonin 5-HT2B receptor (Ki = 13 nM), where it acts as an antagonist.[26] The clinical implications of this, if any, are unclear.[26] In any case, there is no evidence that this action mediates any of the therapeutic effects of amisulpride.[26] Brand names include: Amazeo, Amipride (AU), Amival, Solian (AU, IE, RU, UK, ZA), Soltus, Sulpitac (IN), Sulprix (AU), Midora (RO) and Socian (BR). 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, Mexico, India, New Zealand and Australia (TGA approved in February 2002[1]) to treat psychosis and schizophrenia.[30][31]

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