STUDIES ON PHYSOSTIGMINE AND RELATED SUBSTANCES III. BREAKDOWN PRODUCTS OF PHYSOSTIGMINE; THEIR INHIBITORY EFFECT ON CHOLINESTERASE AND THEIR PHARMACOLOGICAL ACTION

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

1. Rubreserine and eserine blue are strong inhibitors of cholinesterase. On serum cholinesterase in vitro their potency on a molar basis is 1/100th that of physostigmine. Eseroline and eserine brown are devoid of this action.

2. Rubreserine and eserine blue sensitize the leech muscle strip and the rectus abdominis muscle of the frog to acetylcholine. They cause an increase in amplitude of contraction and tonus of the isolated small intestine of the rabbit, a decrease in heart rate of the isolated, denervated mammalian heart, and a constriction of the pupil of the eye of the cat and rabbit. The action upon the isolated gut, heart rate, and pupil of the eye can be abolished promptly and completely by atropine.

3. The maximal twitch height of the calf muscle of the cat in response to single, brief supramaximal condenser discharges was increased by rubreserine and eserine blue in a similar way as with physostigmine.

4. Experiments are reported on the pharmacological action of rubreserine and eserine blue upon normal rabbits and dogs after intravenous injection and on the toxicity of rubreserine, eserine blue, and physostigmine in mice after intravenous injection.

5. Reasons are discussed for the failure of previous investigators to show the pharmacological properties of rubreserine and eserine blue.