Some Observations on the Physical and Pharmacological Properties of Picrotoxin Solutions

Abstract

A slow and spontaneous decrease in pH was observed with freshly prepared aqueous solutions of commercially available picrotoxin and this change was catalysed by the addition of potassium chloride crystals or by contact with a calomel electrode. The pH at which the solution stabilised was dependent upon the original pH of the solvent and the concentration of the solution. Potassium chloride had little effect upon the pH of freshly prepared saline solutions of picrotoxin. There was no difference in pharmacological activity between freshly prepared picrotoxin solutions, solutions after addition of potassium chloride, or solutions which had been stored. Since freshly prepared solutions of pure samples of the two recognised constituents of picrotoxin (picrotoxinin and picrotin) were found to be electrometrically stable, the factor responsible for the change of pH may be an impurity; an impurity was detected in commercially prepared samples of picrotoxin by paper chromatography. Picrotoxinin was the active principle and picrotin was relatively inactive. Slight elevation of the pH markedly reduced the activity of picrotoxin solutions thus supporting an earlier suggestion that for clinical reliability, picrotoxin should be prepared in a buffered solution. No evidence was found to support the belief that Picrotoxin Injection B.P. 1958 should be protected from light.