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.