CHOLINESTERASE STUDIES WITH (R) 3,3-TRIMETHYLINDOLINYL)-N-(1-PHENYLETHYL)CARBAMATE AND -TRIMETHYLINDOLINYL)-N-(1-PHENYLETHYL)CARBAMATE())

A limited number of carbamates have been found useful for treatment of cholinergic symptoms with pyridostigmine and physostigmine being the main focus. In recent years 5-(1,3,3-trimethylindolinyl)N,N-dimethylca rbamate (I) has received considerable attention in the Chinese literat ure for a similar role. We report on the first synthesis of stereoisom ers of an analog of (I). The isomers prepared were (R)( + 3,3-trimethy lindolinyl)-N-(1-phenylethyl)carbamate (II) and 3,3-trimethylindolinyl )-N-(1-phenylethyl)carbamate (III). The pK(a) value for each isomer wa s 6.8. Eel acetylcholinesterase inhibition studies were carried out at 25.0-degrees-C over the pH range of 6.0 to 9.0. They reflect the firs t pH profiles using enantiomorphs of a cholinesterase inhibitor. The i nhibition potencies for (II) and (III) over the range examined were si milar. At pH 7.60 the k(i) for II = 7.38 x 10(3) M-1 min-1 (SD = 398) and for (III) the k(i) = 6.67 x 10(3) M-1 min-1 (SD = 355). In accord with the findings of Wilson and Bergmann20 on physostigmine our result s indicate that the protonated form of (II) and (III) is the more pote nt inhibitor.