The effects of amphetamine isomers on rotarod performance.

The amphetamine isomers impair the rotarod performance of rats in a dose-related manner, with (+)-amphetamine approximately four-times as potent as its (-)-isomer. At a rotation speed of 4 rpm, 60 min after i.p. administration, the TD50 values (mg/kg) were: (+)-amphetamine, 24 (21.9-26.4) and (-)-amphetamine, 96 (76.3-118.4), with the curves not deviating from parallelism. Coadministration of the peripheral cholinesterase inhibitor neostigmine salicylate (0.005 mg/kg) attenuated (+)-amphetamine neurotoxicity [30 (26.4-34.1)]. These results, in conjunction with previously reported effects of the drug on isolated nerve-muscle preparations, suggest that the muscle weakness produced by high doses of amphetamine may result from inhibition of transmission at the neuromuscular junction.