THE SYMPATHOMIMETIC EFFECTS OF 2-PYRIDINE ALDOXIME METHYLCHLORIDE (2-PAM CL)

¹ Department of Pharmacology, Hahnemann Medical College and Hospital, Philadelphia, Pennsylvania

2-Pyridine aldoxime methylchloride has been shown to cause an increase in blood pressure when a dose of 10 mg/kg or more was administered intravenously to dogs. The blood pressure elevation is of a biphasic nature, a transient spike followed by a sustained rise. The first spike is caused by ganglionic stimulation since it is blocked by hexamethonium. Facilitation of ganglionic transmission occurred in the superior cervical ganglion of cats.

The second phase, a sustained pressor effect, is not reduced by hexamethoniunm, atropine, hemtmorrhagic shock or tetraethylpyrophosphate. It is markedly diminished by phenoxybenzamine as well as by pretreatment with reserpine. A 2-PAM Cl induced rise of blood catecholamine levels was shown in dogs receiving a constant infusion of norepinephrine. The rise was similar to that caused by nicotine in time sequence but differed from tyramine since the tyramine rise occurred later, after the peak prossor effect was over. Dose-respomise curves for normal and chronically denervated nictitating membranes of eats showed a reduction of the maximum of the curve after denervation. The second sustained phase of the blood pressure respose of 2-PAM Cl is due to a sympathomimetic action mediated by release of catecholamines or by the prevention of their uptake. In many of its actions 2-PAM Cl resembles nicotine.