THE EFFECT OF PREINCUBATION ON THE INHIBITORY EFFECT OF NEOSTIGMINE AND DIMETHYLCARBAMATE OF (2-HYDROXY-5-PHENYLBENZYL) TRIMETHYLAMMONIUM BROMIDE (RO-2-683) ON THE ENZYMATIC HYDROLYSIS OF PROCAINE

¹ Department of Anesthesia, Mercy Hospital and Section on Anesthesiology, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pa.

1. Preincubation of various concentrations of neostigmine and Ro 2-683 with plasma, markedly influenced their inhibitory effect on the enzymatic hydrolysis of procaine.

2. Preincubation for relatively short periods increased the inhibitory effect of identical concentrations of the same inhibitor.

3. The duration of preincubation necessary for optimal inhibition was shorter with Ro 2-683 than with neostigmine and shorter with the higher inhibitor concentrations than with the lower ones.

4. Only insignificant inhibition was observed when neostigmine and procaine were added simultaneously to the plasmas. Ro 2-683, in higher concentrations, afforded considerable protection against hydrolysis, even when it was added to the plasmas simultaneously with the substrate.

5. Incubation for 24 hours markedly decreased the inhibitory potency of both neostigmine and Ro 2-683, with the exception of the highest concentration.

6. The decrease of the inhibitory potency of neostigmine and Ro 2-683 is probably due to both enzymatic and alkaline hydrolysis of these agents.