STUDIES ON A NEW CHOLINESTERASE INHIBITOR

¹ The Lilly Research Laboratories, Indianapolis 6, Indiana

The pharmacological actions of a new anticholinesterase agent, 4,4’-oxy-bis- (phenacylpyridinium)chloride (No. 21315) were compared with those of neostigmine. The molar concentration producing 50 per cent inhibition of rat brain cholinesterase was found to be 3.16 x 10^-6 and 2.88 x 10^-4 for No. 21315 and neostigmine, respectively. The enzyme-inhibitor complex formed by No. 21315 was more readily dissociated than that produced by neostigmine.

The two compounds were similar pharmacologically with respect to blood pressure and respiratory changes, gut motility, symptoms of toxicity, and duration of action. Both compounds effectively antagonized the action of d-tubocurarine, the onset of action with No. 21315 being more rapid than with neostigmine. At high dosage No. 21315 manifested a neuromuscular blockig action, which was not as pronounced with neostigmine under identical experimental conditions.