Abstract

Purified, authenic isomeric forms of carnitine (Ct) and acetylcarnitine (ACt) were compared with choline and acetylcholine. Mean log dose-response curves for the degree of isometric contracture of isolated frog rectus abdominis muscle showed that choline was more potent than l- or d-ACt and that these were more potent than l- or d-Ct. d- Turbocurarine, 1.4 x 10^-6 M, shifted the dose-response curves for l-ACt, d-ACt and acetyicholine one log unit parallel to the right without depressing the maximal response, indicating competitive antagonism. The Ct's and ACt's were neither anticholinesterases nor substrates for cholinesterases. Nicotinic action of the ACt's was principally at the neuromuscular junction. They blocked transmission in the cat anterior tibialis muscle by depolarization like other quatennary ammonium compounds and augmented the effects of other depolarizing blockers. Their muscaninic activity was limited to effects on salivation, pupil diameter and blood pressure and was blocked by atropine. The ACt's more closely resembled choline than acetylcholine in potency and duration of action. The increased potency resulting from acetylating Ct suggests that electrophilic or cationic sites of the receptor may be as important as the anionic sites where drug-receptor interactions are considered to occur for cholinergic or anticholinergic actions.