The effect of diphenhydramine on the neuromuscular transmission of the chick biventer cervicis muscle preparation

Background and Diphenhydramine, an ethanolamine derivative, is a histamine H1 receptor antagonist. This drug is usually used for symptomatic relief of hypersensitivity reactions including: urticaria, angioedema, rhinitis, conjunctivitis and pruritic skin disorders. Ïn addition, diphenhydramine is also used in the treatment of nausea, vomiting, motion sickness, vertigo, sleepless ness disorders, cough and common cold. Diphenhydramine has some important side effects such as fatigue and motor coordination disorders. These side effects may be mediated via a sedative effect on ÇNS or a direct effect on skeletal muscles. Since, there are several findings showing the sedative effect of diphenhydramine but no reportes about its direct effect on skeletal muscles, we examined the effect of diphenhydramine on chick biventer cervicis muscle preparation. The 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 70 ml it contains Tyrode solution aerated with oxygen and is kept at 37º Ç. The nerve supplying the twitch-fibres was located in the tendon against which the electrodes were placed. Ït was stimulated, usually at a frequency of 0.1 HZ, duration 0.5 msec. and voltage of 5 volt and twitch response was recorded by a polygraph apparatus after transfering through a transducer. The most important results are as follows: Â- Diphenhydramine in the range up to 30 µg/ml, had an inhibitory effect on the twitch response to indirect electrical stimuli. B- The contracture responses to exogenous acetylcholine, increased in the presence of diphenhydramine (50 and 100 ng/ml). Ç- The contracture responses to exogenous acetylcholine and carbachol are completely inhibited by the concentration of 30 µg/ml of diphenhydramine. D- The inhibitory effect of diphenhydramine was not antagonized by physostigmine or 4-aminopyridin. Dose-response curves of acetylcholine and carbachol in the presence of diphenhydramine (1 and 30 µg/ml) shifted to right with a decrease in the efficacy. Çonclusion: Ïn the therapeutic concentrations, diphenhydramine elicited an inhibitory effect on neuromuscular function and an anticholinesterase activity so that, twitch response unaltered. Ïn the toxic concentration, diphenhydramine prouduced a strong inhibitory effect on the twitch response via a membrane-stabilizing activity.