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  • Title: Dopamine receptor pharmacology.
    Author: Seeman P, Van Tol HH.
    Journal: Curr Opin Neurol Neurosurg; 1993 Aug; 6(4):602-8. PubMed ID: 8104554.
    Abstract:
    Although antipsychotic drugs originally helped to discover dopamine receptors, the five dopamine receptors presently identified and cloned are facilitating the search for and discovery of more selective antipsychotic and antiparkinson drugs. The D1-like dopamine receptors, D1 and D5, are sensitive to the same drugs as the D1 receptor in native tissues, but D5 is about 10 times more sensitive to dopamine than D1. The D2-like receptors, D2, D3, and D4, have approximately similar sensitivities to dopamine, but bromocriptine and raclopride are both about two orders of magnitude weaker at D4, whereas clozapine is one order more potent at D4, as compared with D2 and D3. The human dopamine D4 receptor has many variants. The sensitivities to clozapine of human variants D4.2, D4.4, and D4.7 are approximately similar, with dissociation constants between 5 and 24 nM, matching the spinal fluid concentration of clozapine under therapeutic conditions. Thus antipsychotic action may be effected through blockade of either dopamine D2 or D4 receptors.
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