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• W1972607143 abstract "Interactions with 5-HT2A and 5-HT2C receptors may be important for the actions of atypical antipsychotic drugs, such as clozapine (CLOZ). In this study we characterized the interaction of chlorpromazine (CPZ) and three putative atypical antipsychotic drugs, risperidone (RIS), amperozide (AMP), and ORG 5222 (ORG) with the 5-HT2A and the 5-HT2C receptor. CLOZ was used as a reference agent. These agents had 5-HT2C receptor-binding affinities (Ki values) in the following rank order: ORG (0.9 nM) > CLOZ (13.2 nM) > or = CPZ (27.1 nM) > RIS (112 nM) > > AMP (2580 nM). RIS (1.9 nM) and AMP (75.6 nM) had clearly higher affinities for the 5-HT2A than the 5-HT2C receptor; otherwise the 5-HT2A and 5-HT2C receptor affinities were approximately the same. Phosphoinositide hydrolysis studies in the rat choroid plexus revealed that all these agents were 5-HT2C receptor antagonists, with an approximately similar rank order of potency compared to the 5-HT2C receptor-binding data. Quantitative receptor autoradiography was used to study the regulation of 5-HT2A and 5-HT2C receptors after chronic treatment (14 days, SC injections once a day) with CLOZ (25 mg/kg), CPZ (15 mg/kg), RIS (0.3 mg/kg), AMP (5 mg/kg), and ORG (0.1 mg/kg). In the doses used, CLOZ, CPZ, and ORG decreased the frontal cortical 5-HT2A receptor binding of [3H]ketanserin and [125I]DOI by 40% to 60%. AMP also significantly decreased 5-HT2A receptor [3H]ketanserin binding by 30%, whereas RIS did not affect 5-HT2A receptor binding. In contrast to 5-HT2A receptors, only CLOZ significantly (by about 50%) decreased 5-HT2C receptor [3H]mesulergine and [125I]DOI binding in the choroid plexus. For comparison, CPZ was the only drug to significantly upregulate striatal D2 receptor-binding sites, whereas none of the drugs affected striatal D1 receptors. The main finding in this study is that 5-HT2A and 5-HT2C receptors are differentially regulated after chronic treatment with CLOZ, CPZ, RIS, AMP, and ORG." @default.
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• W1972607143 date "1995-10-01" @default.
• W1972607143 modified "2023-10-17" @default.
• W1972607143 title "Differential Regulation of Rat 5-HT2A and 5-HT2C Receptors after Chronic Treatment with Clozapine, Chlorpromazine and Three Putative Atypical Antipsychotic Drugs" @default.
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• W1972607143 doi "https://doi.org/10.1016/0893-133x(95)00049-j" @default.
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