STUDIES ON PHYSOSTIGMINE AND RELATED SUBSTANCES II. THE DESTRUCTION OF PHYSOSTIGMINE IN BUFFERED SOLUTIONS AND IN SERUM

¹ From the Department of Pharmacology, Harvard Medical School, Boston

1. A method is reported for the quantitative estimation of physostigmine at concentrations between 10^–6 and 10^–8 molar. This method depends upon the quantitative relation of the inhibition of serum cholinesterase activity to the physostigmine concentration in the above range of inhibitor concentration.

2. A colorimetric method for the estimation of physostigmine is described.

3. The decomposition of physostigmine in buffered solutions at pH 5-9 has been studied. The rate of destruction is a reflection of the physostigmine and hydroxyl ion concentrations.

4. The rate of serum inactivation of physostigmine has been shown to be related to the concentration of both the drug and the cholinesterase activity when the serum activity is greater than 15-20% of the normal uninhibited activity. When the physostigmine concentration is sufficient to depress the cholinesterase activity more completely, the rate of physostigmine destruction is slow. This is interpreted as an inhibition due to excess substrate (physostigmine).