Majallah-i Dānishgāh-i ̒Ulūm-i Pizishkī-i Bābul (Oct 2003)
Effect of Dextromethorphan on the neuromuscular transmission of the chick biventer cervicis muscle preparation
Abstract
Background and Objective: Dextromethorphan is a well-known over-the-counter antitussive drug with over 45 years of clinical usage experience. Its toxicity is low, but extremely high doses may produce muscle or CNS depression, drowsiness and gastrointestinal upset. In the present study, the effect of dextromethorphan on the neuromuscular transmission of isolated chick biventer cervicis muscle preparation was examined. Methods: This isolated chick (About 3 weeks old) biventer cervicis muscle was put in the organ bath. The organ bath had a vessel with volume of about 70ml, it contained tyrode solution aerated with oxygen and was kept at 37°C. The nerve supplying the twitch-fibers was located in the tendon against which the electrodes were placed. It was stimulated usually at a frequency of 0.1 HZ, duration of 0.5 msec. and voltage of 5-10 volt and twitch response was recorded by a polygraph apparatus after transferring through a transducer. Findings: Dextromethorphan in the range of 2.5 to 5.4 µM has an inhibitory effect on the twitch response to indirect electrical stimuli and contracture of exogenous acetylcholine. The inhibitory effect of dextromethorphan was not antagonized by physostigmine or 4-aminopyridin. Potentiation to twitch response due to 10 fold greater duration of the stimuli was decreased by dextromethorphan. Both tetanosis and facilitating after tetanosis were inhibited in the presence of dextromethorphan. Twitch response to the direct electrical stimuli was inhibited by dextromethorphan. Caffeine significantly antagonized the inhibitory effect of dextromethorphan on the twitch response to indirect electrical stimuli. Dose-response curves of acetylcholine and carbachol in the presence of dextromethorphan shifted to right with a decrease in the efficacy. Conclusion: These results suggested that the inhibitory effect of dextromethorphan on the neuromuscular transmission of the chick biventer cervicis muscle is mediated through blockade of sarcoplasmic reticulum calcium channels.
