GANGLIOPLEGIC ACTIVITY OF DI-TERT.-BUTYLNITROXIDE, A STABLE FREE RADICAL, AND ANALOGUES

¹ Department of Experimental Pharmacology, Experimental Therapeutics Research Section, Lederle Laboratories Division, American Cyanamid Co., Pearl River, New York

Various tests demonstrated that di-tert.-butylnitroxide, a permanently stable free radical, possesses potent, oral, ganglioplegic activity. In studying the pharmacology of 15 congeners, it was found that ganglionic blockade was not restricted to compounds with a free electron; certain analogues with conventional physicochemical properties produced a similar action. Sufficient shielding of the basic nitrogen atom appeared to be of major importance.

Blockade of nerve impulse transmission across sympathetic ganglia was suggested by the concomitant augmentation of the epinephrine and phenethylamine vasopressor responses and reduction of the mean blood pressure of rats following oral treatment. More definitive evidence was revealed by the ability of di-tert.-butylnitroxide and di-t-butylhydroxylamine HCl to inhibit the increased contractility of the nictitating membrane, urinary bladder and myocardium to preganglionic stimulation but not to stimulation of either the postganglionic nerves or the effector organ. In addition, normal postganglionic potentials could not be elicited by preganglionic stimnulation of the superior cervical and ciliary nerves after injecting the compounds.