Relationship between occupation of cerebral H1-receptors and sedative properties of antihistamines. Assessment in the case of terfenadine
Rose, C.; Quach, T.T.; Llorens, C.; Schwartz, J.C.
Arzneimittel-Forschung 32(9a): 1171-1173
1982
ISSN/ISBN: 0004-4172 PMID: 6129863 Document Number: 193861
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.