NEUROMUSCULAR BLOCKING ACTIVITY AND OTHER PHARMACOLOGIC PROPERTIES OF VARIOUS CARNITINE DERIVATIVES

¹ Department of Biochemistry, McGill University, Montreal, Canada

Although carnitine has long been known to be present in the body, little is known of its physiologic function. Acetylcarnitine also is present in the body and has important biochemical properties but its cholinomimetic properties are not clear. Carnitine has two sites for ester formation and a variety of mono- and diester derivatives of it have been prepared and tested for: a) neuromuscular blocking activity on the isolated rat phrenic nerve-diaphragm and frog sciatic nerve-gastrocnemius muscle preparations; b) acetylcholine-like activity on cat blood pressure, guinea-pig ileum and physostigmine-treated frog rectus muscle; and c) hydrolysis by the cholinesterases. It was found that while certain carboxyl group derivatives of carnitine and acetylcarnitine, e.g., nitrile, ethyl chloride and choline, were potent neuromuscular blockers, they were less active than d-tubocurarine, decamethonium and succinylcholine. Acetyl-dl-carnitylcholine has one-eighth the acetylcholine-like activity of acetylcholine and the ratio of its nicotinic to its muscarinic activity is unity. True cholinesterase rather than pseudocholinesterase partly destroys acetyl-dl-carnitylcholine. This destruction is completely inhibited by physostigmine.