Pharmacological analysis of the neuromuscular properties of diethylcarbamazine citrate in vitro

Abstract

The actions of diethylcarbamazine citrate (DECC) have been examined on agonist- and electrically-induced contractures and twitches of the isolated chick biventer cervicis and rat phrenic nerve-hemidiaphragm muscle preparations in order to analyse the effects of this commonly-prescribed anthelmintic drug at the neuromuscular junction. DECC (5 x 10(-1)-1.5 mM) produced a concentration-dependent initial augmentation of the indirect electrically-evoked twitches followed by a sustained, longer-lasting secondary depression of the twitches of all the skeletal muscle-nerve preparations examined. The DECC-induced twitch depression was competitively reversed by increasing the bathing fluid calcium ion concentration (Ca2+). DECC (10(-3)-2.5 x 10(-2) M) caused marked augmentation of the contractural responses of innervated chick biventer muscle preparations induced by bath-applied low concentrations of carbachol, acetylcholine or nicotine, and depressed those contractural responses of the muscle elicited by hgh concentrations of the agonists. On their own accord, high concentrations of DECC (10(-1)-2.5 mM) dose-dependently contracted isolated chick biventer cervicis muscle preparations, and demonstrated measurable anticholinesterase activity. It is concluded that DECC has both direct (post-junctional) and indirect (pre-junctional) effects at the neuromuscular junction, and that the neuromuscular blockade produced by this anthelmintic agent is probably post-junctional in origin.