Dissociation between central and peripheral antihistamine activities of the new antiallergic agent N-[4-[4-(diphenylmethyl)-1-piperazinyl]-butyl]-3-(6-methyl-3-pyridyl) acrylamide in rats and monkeys.

In order to examine the penetration of N-[4-[4-(diphenylmethyl)-1-piperazinyl]-butyl]-3-(6-methyl-3-pyrid yl) acrylamide (AL-3264, CAS 118420-47-6), a new antiallergic agent, into the brain, the antihistamine activities in the central and peripheral tissues from the rats and monkeys orally treated with AL-3264 were measured in comparison with those of ketotifen, oxatomide, mequitazine and terfenadine. These 5 drugs dose-relatedly suppressed the histamine-induced dye leakage in the rat skin and, except terfenadine, inhibited the binding of 3H-mepyramine to brain homogenates obtained from the rats treated orally with the drugs. The ratio (0.07) of AL-3264 for the central (3H-mepyramine binding) to peripheral (dye leakage) antihistamine activities was lower than that of ketotifen, oxatomide and mequitazine, and higher than that of terfenadine. The serum and cerebrospinal fluid (CSF) samples, which were collected from the monkeys treated with 80 mg/kg p.o. of AL-3264, terfenadine or oxatomide, inhibited the histamine-induced contractions in isolated guinea pig trachea. The ratio (0.003) of AL-3264 for the central (CSF) to peripheral (serum) antihistamine activities was lower than that of terfenadine and oxatomide. These results suggest that AL-3264 is poorly accessible to the brain, and may be regarded as a non-sedative antiallergic agent.