Relationship between occupation of cerebral H1-receptors and sedative properties of antihistamines. Assessment in the case of terfenadine.
Alpha-[4(1,1-Dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1- piperidinebutanol (terfenadine, RMI 9918, Triludan, Teldane, resp.) inhibits the in vitro binding of [3H]mepyramine to H1-receptors in cerebral membranes with an apparent dissociation constant in good agreement with that found for antagonism of histamine-induced contractions of guinea pig ileum. In contrast, administration of terfenadine in therapeutic dosage does not result in the occupation of cerebral H1-receptors in the living mouse, as observed for most H1-antihistamines. A poor access of the drug to cerebral H1-receptors might account for the absence of sedative side effects.
D000818:Animals; D001559:Benzhydryl Compounds / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000378:metabolism / Q000494:pharmacology*; D006993:Hypnotics and Sedatives; D066298:In Vitro Techniques; D011968:Receptors, Histamine / Q000378:metabolism*; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D016593:Terfenadine
D001559:Benzhydryl Compounds; D006634:Histamine H1 Antagonists; D006993:Hypnotics and Sedatives; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D016593:Terfenadine