Amisulpride: limbic specificity and the mechanism of antipsychotic atypicality.
Amisulpride clearly has the clinical profile of an atypical antipsychotic, characterised in particular by its lower propensity to induce extrapyramidal side effects as well as its greater efficacy in treating negative symptoms compared with classical neuroleptics. In addition to the clinical advantages over classical neuroleptics, it has also been demonstrated that the clinical profile of amisulpride is comparable to that of other modern atypical neuroleptics. Animal data also allow the conclusion to be drawn that amisulpride has an atypical profile. For example, amisulpride does not provoke catalepsy which is characteristic of postsynaptic D2 blockade in the rat. The induction of catalepsy in animal models is usually seen as an indicator of the propensity to induce extrapyramidal side effects in patients. In relation to the widely accepted hypothesis that the inclusion of 5-HT2A antagonism in addition to D2 antagonism is of great relevance for the atypicality of an antipsychotic, and given the fact that amisulpride lacks 5-HT2A antagonism, the pharmacological explanation of the clinically well-proven atypicality of amisulpride is of great interest. Based on basic research and in vivo imaging studies, two mechanisms in particular seem to explain the atypicality of amisulpride: preferential action on limbic D2/D3 receptors and preferential blockade of presynaptic D2/D3 receptors. In addition, the fast dissociation hypothesis can contribute to the explanation of the atypical clinical profile of amisulpride. The relevance of the D3 blockade in the context of atypicality is not yet completely clear.
Möller
Hans-Jürgen
HJ
Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336 Munich, Germany. hans-juergen.moeller@psy.med.uni-muenchen.de
D000077582:Amisulpride; D000818:Animals; D014150:Antipsychotic Agents / Q000097:blood / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002375:Catalepsy / Q000188:drug therapy; D004213:Dissociative Disorders; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008032:Limbic System / Q000033:anatomy & histology / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017661:Receptors, Presynaptic; D013469:Sulpiride; D000077582:Amisulpride