Some Pharmacological Properties of Trimethoxy Analogs of Pheniramine, Tripelennamine, and Diphenhydramine

Trimethoxy analogs of tripelennamine, diphenhydramine, and pheniramine were studied to determine the influences of the trimethoxy group on the pharmacological activity of known antihistamines. In this investigation, the ability of the parent compounds and their analogs to antagonize the histamine-induced contractions of guinea pig ilia were studied as well as their effects on the systolic blood pressure of male albino rats and on the central nervous system of mice as measured by the actophotometer. The trimethoxy analogs were comparatively weak competitive antagonists of histamine with the exception of N,N,-Diethyl-N\u27(2-pyridyl)-N\u27-(3,4,S-trimethoxybenzyl) ethylenediamine Dicyclamate (De-TMPBZ) and N,N,-Diethyl-N\u27-(2-pyridyl)-N\u27-(3,4,5-trimethoxybenzyl) ethylenediamine Disuccinate (TMPBZ) which were weak noncompetitive histamine antagonists. The parent compounds and their analogs did not significantly alter the systolic blood pressure of rats, but they did cause some minor fluctuations which were of interest. Intraperitoneal injections of pheniramine in mice caused a significant increase (P\u3c=0.05) in locomotor activity, but Dma-TMPP, a trimethoxy analog of pheniramine, did not significantly alter locomotor activity. Injections of tripelennamine produced no significant changes in locomotor activity; however, Mor-TMPBZ, a trimethoxy analog of tripelennamine caused a significant decrease in activity