期刊
EXPERT REVIEW OF CLINICAL PHARMACOLOGY
卷 -, 期 -, 页码 -出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/17512433.2023.2274538
关键词
Schizophrenia; bipolar disorder I; major depressive disorder; amisulpride; antipsychotics; antidepressants
_SEP-4199 is a potential breakthrough for managing depressive symptoms in bipolar disorder I, with enhanced efficacy and reduced side effects compared to traditional antipsychotic drugs. The selective D2 receptor binding of SEP-4199 enhances antidepressant effects while minimizing extrapyramidal side effects. Further research on D2 and D3 receptor-mediated effects may lead to improved treatment strategies for psychiatric disorders._
IntroductionThe challenges posed by treatment-resistant schizophrenia and depressive symptoms have led to ongoing difficulties despite the availability of antipsychotics and antidepressants. This review addresses the potential of amisulpride analogs, particularly SEP-4199, in addressing these challenges through enhanced efficacy and reduced side effects.Areas coveredThis review focuses on the pharmacological profile of amisulpride analogs, exemplified by LB-102 and its derivative SEP-4199. PubMed gathered articles (up to 10 March 2023) on 'amisulpride,' 'schizophrenia,' 'bipolar disorder,' and 'major depressive disorder;' ClinicalTrials.gov tracked SEP-4199 and LB-102 trials. LB-102, a newly identified N-methylated analog of amisulpride, exhibits enhanced lipophilicity at lower doses, as demonstrated in a phase 1 study, indicating significant promise for therapeutic applications. The discovery of SEP-4199, a non-racemic analog composed of R- and S-enantiomers in an 85:15 ratio, is discussed, emphasizing its potential to enhance antidepressant effects while minimizing extrapyramidal side effects via selective D2 receptor binding. Recent phase 2 trials have demonstrated SEP-4199's efficacy in treating depressive symptoms in bipolar disorder I, capitalizing on D2-mediated anti-anhedonic and D3-mediated reward effects.Expert opinionThe development of SEP-4199 presents a potential breakthrough for managing depressive symptoms in bipolar disorder I. Further exploration of D2 and D3 receptor-mediated effects could lead to improved treatment strategies.
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