PHARMACOLOGICAL PROPERTIES OF SOME NEOSTIGMINE ANALOGS

¹ Pharmacology Department, Hoffmann-La Roche Inc., Nutley 10, N. J.

A series of twenty neostigmine analogs has been studied for relative pharmacological activity. The phenolic compound, 3-hydroxy phenyltrimethylammonium bromide (Ro 2-2561) has strong anti-curare action but minimal cholinergic action and low toxicity. The acetyl derivative has similar anti-curare action but increased cholinergic action and lower toxicity. The benzoyl derivative has similar anti-curare action but less cholinergic action and lower toxicity. Substitutions in the benzoyl group such as CH₃, Cl, NH₂, NO₂ do not improve the anti-curare action. The 2- and 4-benzoyl esters, the cyclohexyl, benzoyl and phenethyl derivatives and the unsubstituted phenyl derivatives have less activity.