Some pharmacological properties of a novel series of 2-substituted 2-phenylcyclohexyl N,N-diethylaminoethyl ethers I.

Two 2-phenylcyclohexyl N,N-diethylaminoethyl ethers were studied for their pharmacological actions in vitro-the cis- and trans- isomers; and in vivo,-the cis- isomer. These compounds (5 mg/ml) significantly depressed acetylcholine-induced contractions in the isolated guineapig ileum. The trans- isomer produced a greater depression of contraction. The cis- isomer shortened the duration of methacholine-induced salivation in mice when administered intraperitoneally in increasing doses. The duration was found to be inversely proportional to the dose of the compound. In anesthetized rats, pretreatment with either a dose of 5 mg/Kg of the cis- compound or 0.25 mg/Kg of atropine changed the methacholine depressor response to a pressor response. Heart rate was increased in both groups of pretreated rats. Respiratory rate was further augmented by methacholine in the presence of either atropine or the cis- compound, while rectal temperature was slightly decreased. Effects of the cis- isomer when administered alone, on heart rate and blood pressure responses usggest cholinergic activity. However, its ability to decrease the duration of methacholine-induced salivation in mice and its reversal of methacholine-evoked cardiovascular effects are indicative of anticholinergic activity. These experiments suggest that the cis- isomer has a mixed cholinergic and anticholinergic action and thus may be classed as a partial antagonist of the parasympathetic system.