Serotonin sensitive adenylate cyclase activity in monkey anterior limbic cortex: antagonism by molindone and other antipsychotic drugs. |
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Authors: | H S Ahn M H Makman |
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Institution: | Departments of Biochemistry and Molecular Pharmacology Elbert Einstein College of Medicine Bronx, New York 10461, USA |
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Abstract: | Serotonin (5-HT) sensitive adenylate cyclase in monkey anterior limbic cortex homogenates was further characterized and the effects of antipsychotic drugs and 5-HT anatagonists investigated. Differences in time course for stimulation by agonists and in responsiveness to receptor anatagonists of 5-HT-and dopamine (DA)-stimulated activities, were observed. Also there was an additivity of 5-HT and DA at maximally effective concentrations. Classical 5-HT antagonists blocked the 5-HT sensitive adenylate cyclase with a rank order of potency: methiothepin > cyproheptadine > methysergide. These 5-HT antagonists also effectively inhibited DA sensitive adenylate cyclase. Most antipsychotic drugs tested antagonized 5-HT stimulated activity although these drugs exhibited greater efficacies in blocking DA stimulated activity. Exceptions were molindone which failed to antagonize DA sensitive adenylate cyclase but effectively blocked 5-HT sensitive cyclase and pipamperone which was inactive in both cyclase systems. Haloperidol was a more selective antagonist of the DA sensitive adenylate cyclase than were the other antipsychotic drugs tested. |
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