Selective displacement of [3H]mepyramine from peripheral vs. central nervous system receptors by loratadine, a non-sedating antihistamine.

Displacement of [3H]mepyramine binding was compared in membranes from guinea-pig lung vs. cerebral cortex as a measure of affinity for peripheral vs. central nervous system (CNS) histamine receptors. Loratadine, a new non-sedating antihistamine, was found to be the only compound tested which was selective for lung (Ki = 35 nM) vs. cortex (Ki = 118 nM). This difference is statistically significant (P less than 0.05) whereas there was no significant (P greater than 0.05) difference in the Kis between the 2 tissues for terfenadine, astemizole, mequitazine or chlorpheniramine. It is concluded from these and other studies that the lack of significant sedative effects shown with loratadine is due to its poor penetration into the CNS and selectivity for peripheral histamine receptors.