Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites.
In vitro binding affinities of chlorpromazine, fluphenazine, levomepromazine, perphenazine and some of their metabolites for dopamine D2 receptors, alpha 1- and alpha 2 adrenoceptors in rat brain were previously reported from our laboratories. The present study reports the in vitro binding affinities of the same compounds for muscarinic cholinergic receptors and for histamine H1 receptors in rat brain, using 3H-quinuclidinyl benzilate and 3H-mepyramine as radioligands. Chlorpromazine, levomepromazine, and their metabolites had 5-30 times higher binding affinities for muscarinic cholinergic receptors than fluphenazine, perphenazine and their metabolites. Levomepromazine was the most potent and fluphenazine the least potent of the four drugs in histamine H1 receptor binding. 7-Hydroxy levomepromazine, 3-hydroxy levomepromazine and 7-hydroxy fluphenazine had only 10% of the potency of the parent drug in histamine H1 receptor binding, while the 7-hydroxy-metabolites of chlorpromazine and perphenazine had about 75% of the potency of the parent drug in this binding system. Their histamine H1 receptor binding affinities indicate that metabolites may contribute to the sedative effects of chlorpromazine and levomepromazine.
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CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-Y CHEMICAL GENE-N GENE-N GENE-Y GENE-N GENE-Y GENE-Y GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
fluphenazine levomepromazine fluphenazine levomepromazine perphenazine Levomepromazine fluphenazine histamine 7-Hydroxy levomepromazine perphenazine histamine 3-hydroxy levomepromazine 7-hydroxy fluphenazine histamine 7-hydroxy chlorpromazine perphenazine histamine phenothiazine histamine H1 receptor dopamine D2 receptors chlorpromazine alpha 1- and alpha 2 adrenoceptors muscarinic cholinergic receptors histamine H1 receptors muscarinic cholinergic receptors histamine H1 receptor histamine H1 receptor histamine H1 receptor levomepromazine dopamine chlorpromazine histamine 3H-quinuclidinyl benzilate 3H-mepyramine Chlorpromazine