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  • Title: Multiple actions of phencyclidine: discriminant structure-activity relationships from molecular conformations and assay conditions.
    Author: Weinstein H, Maayani S, Pazhenchevsky B.
    Journal: Fed Proc; 1983 Jun; 42(9):2574-8. PubMed ID: 6303861.
    Abstract:
    A major approach to the elucidation of the mechanisms by which phencyclidine (PCP) elicits the varied and complex responses observed in biological systems consists of comparisons of the pharmacological profiles of PCP derivatives with those of drugs for which the mechanism of action is better understood. Such studies depend on the definition of discriminant structure-activity relationships and on comparisons of rank orders of potency for the actions of PCP derivatives. Using the muscarinic cholinergic system in brain and the potassium ion channels in cardiac muscle as targets for PCP derivatives, we review the elucidation of the structural determinants for PCP recognition at muscarinic receptors, and the dramatic effect of assay conditions on the rank order of potency for the action of PCP derivatives at intracellular sites. The structural and physicochemical considerations illustrated here must be considered basic to the establishment of any assay aimed at the elucidation of the mechanism of action of PCP.
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