Antipsychotic activity of substituted gamma-carbolines.
Basic Information
ID: ALA1123617
Journal: J Med Chem
Title: Antipsychotic activity of substituted gamma-carbolines.
Authors: Abou-Gharbia M, Patel UR, Webb MB, Moyer JA, Andree TH, Muth EA.
Abstract: Several novel substituted gamma-carbolines were synthesized and examined in a series of in vitro and in vivo pharmacological tests to determine potential antipsychotic activity. Most compounds were orally active in blocking the conditioned avoidance response (CAR) in rats but did not antagonize apomorphine-induced stereotyped behavior. Compound 17 (Wy-47,384), a gamma-carboline with a 3-(3-pyridinyl)propyl side chain, was selected for development as an atypical antipsychotic agent because of its potent and selective profile in preclinical psychopharmacological tests. It blocked CAR in rats with an AB50 of 14 mg/kg po, showed weak affinity for the D2 receptor site (Ki = 104 nM), and showed differential potency in antagonizing apomorphine-induced stereotyped behavior (ED50 = 11 mg/kg ip) and climbing behavior (ED50 = 4 mg/kg ip). Such activities are suggestive of antipsychotic efficacy combined with a low potential for extrapyramidal side effect (EPS) liability.
CiteXplore: 2888898
DOI: 10.1021/jm00393a023
Patent ID: ┄