Acetylcholinesterase inhibition by sulphur and selenium heterosubstituted isomers of N,N-diethylcarbamyl choline and carbaryl.

Nine sulphur and selenium heterosubstituted isomers of N,N-diethylcarbamylcholine and carbaryl have been prepared and their inhibiting activity towards electric eel acetylcholinesterase (E.C. 3.1.1.7) have been measured. The N,N-diethylcarbamylcholines acted only as reversible inhibitors, i.e. they could not carbamylate the enzyme. The reversible inhibition was of mixed type. Sulphur and selenium substitution had only marginal effects on Ki(0.2-0.3 mM) but reduced the value of K'i. The heterosubstituted carbaryl analogues were, with one exception, found to be irreversible inhibitors, about 100 times less potent than carbaryl.

Synthesis and spectroscopic characterization of acetyl-Clx (x = 0,1,2 or 3) and nitroso derivatives of carbaryl and three possible metabolites.

Acetyl-Clx (x = 0,1,2 or 3) and nitroso derivatives of carbaryl, 1-naphthol. 5-hydroxycarbaryl, and 1,5-naphthalenediol were synthesized. Compounds were characterized by infrared, mass, and nuclear magnetic resonance spectroscopy. N-chloroacetylation (Cl = 0,1,2, or 3) of carbaryl was readily accomplished through the pyridine-catalyzed reaction of carbaryl with the appropriate acid chlorides. Trichloroacetylation was also possible through the pyridine-catalyzed reaction with the anhydride. N-nitrosation could also be done readily. N-nitroso- and N-trichloroacetyl carbaryl underwent decomposition to carbaryl on exposure to atmosphere moisture and could be maintained in the pure state only with difficulty. The other derivatives were stable under normal storage conditions.