The changing pharmacodynamics of metocurine identify the onset and offset of canine gastrocnemius disuse atrophy.
BACKGROUND
Immobilization of skeletal muscle results in disuse atrophy and resistance to nondepolarizing muscle relaxants. We studied the pharmacodynamics of metocurine (MTC) to identify the development and recovery of disuse-related resistance to MTC.


METHODS
Nineteen dogs underwent cast immobilization of a hind limb for as long as 3 weeks. Before, during, and after casting, dogs were intermittently anesthetized with thiamylal-N2O-fentanyl. The blood concentration of MTC and the corresponding degree of paralysis after a brief infusion were recorded and were used to characterize the pharmacokinetics and pharmacodynamics of MTC.


RESULTS
Pharmacodynamic study of the response to MTC demonstrated resistance by the 4th day of casting. The effect-site concentration associated with 50% paralysis of twitch increased after 3 weeks from approximately 250 to 750 ng/ml. After cast removal, resistance persisted for 2 more weeks. Six weeks after cast removal, the effect-site concentration associated with 50% paralysis of twitch was normal in every dog.


CONCLUSIONS
Within the context of this study of immobilization disuse atrophy, pharmacokinetic and pharmacodynamic characterization of antagonist responses can be used to infer muscle disuse-related changes in acetylcholine receptors.
Fung
D L
DL
Department of Anesthesiology, University of California School of Medicine, Davis 95616-8634, USA.
White
D A
DA
Gronert
G A
GA
Disbrow
E
E
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D007103:Immobilization; D009133:Muscular Atrophy / Q000503:physiopathology*; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*; D011950:Receptors, Cholinergic / Q000502:physiology; D014403:Tubocurarine / Q000031:analogs & derivatives* / Q000494:pharmacology
D003473:Neuromuscular Nondepolarizing Agents; D011950:Receptors, Cholinergic; D000109:Acetylcholine; C032943:metocurine; D014403:Tubocurarine