Cholinergic-independent effects of amphetamine on mammalian skeletal muscle contractions.
Studies were designed to investigated the cholinergic-independent mechanism(s) by which (+)-amphetamine produces a biphasic modification of directly stimulated contractions of skeletal muscle in the rat phrenic nerve-diaphragm preparation. In tissues pretreated with alpha-bungarotoxin, low concentrations of (+)-amphetamine (2.7-1.08 x 10(-4) M) enhanced muscle blockade. In other studies (Gerald, Meldrum and Skau, Res. Commun, chem. Path. Pharmac., 1982), high K+ concentrations or low Na+ concentrations antagonized amphetamine-enhancement of the twitch, while potentiating the blockade; in contrast K+-free media augmented amphetamine-induced enhancement of contractions. Low concentrations of amantadine, tetracaine, and tetrodotoxin increased the facilitatory response to (+)-amphetamine while the inhibitory effects of (+)-amphetamine were potentiated by higher concentrations of these antagonists; similar biphasic effects were observed with (-)-amphetamine and tetracaine. (+)-Amphetamine reserved the marked enhancement of the twitch produced by veratridine while, conversely, this neurotoxin failed to alter muscle contractions after (+)-amphetamine pretreatment. These findings suggest that amphetamine-induced enhancement and blockade of directly-stimulated skeletal muscle resulted from alterations in Na+ fluxes, possibly through interactions with membrane ionic channels.
D000547:Amantadine / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D003964:Diaphragm / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000502:physiology; D010791:Phrenic Nerve / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains / Q000502:physiology; D013748:Tetracaine / Q000494:pharmacology
D000662:Amphetamines; D002038:Bungarotoxins; D013748:Tetracaine; D000547:Amantadine