The Effect of Chloroquine on the Smooth. Cardiac and Skeletal Musclej: a Re-evaluation

The e ffect of chloroquine on the responses of smooth, cardiac and skeletal muscles to various drugs have been investigated using small laboratory animal3 such as guinea pigs, rats and rabbits. In a ll cases, isolated tissues were used. In addition, the e ffec t of intraperitoneal ( IP ) administration o f chloroquine on pregnant rats was undertaken, to investigate its alleged abortifacient action. In this investigation, the dose-response relationship, the possible mechanism of action and its implication are discussed. Ghloroquine was found to have the following properties:a) Relaxes the tracheal smooth muscles and opposes the constsictor e ffec t o f acetylcholine (Ach), histamine, nicotine and barium chloride on the guinea p ig trachoal smooth muscles. b) Causes short-lived relaxation of rabbit i le a l muscles and antagonizes the spontaneous contractior/ninduced by acetylcholine, nicotine and barium chloride possibly by membrane stabilization and local anaesthetic properties. o) Exhibits negative inotropio and chronotorpic e ffects on the isolated rabbit heart and opposes the positive chronotropic responses due to adrenaline and isoprenaline probably by p iadrenergic blocking activ ity . j.t also antqg&izes the cardiostimulant action of caffeine and barium chloride. “Hie negative chronotropic action could oe the basis of i t s well known antiarrhythmie property, d ' In addition to causing depression o f neuromuscular transmission, chloroquine potentiates the neuromuscular blocking e ffe c t of tubocurarine succinylcholine andlignocaLne probably by a non—specific interference with ion ic conductance. 2 e) Chloroquine has no uterotonic activ ity of its own, but inhibits the contractions of rat uterine smooth muscles induced by carbachol, oxytocin and prostagland (PGP2^) (prostin) probalby by extensive, non-specific interference with calcium conductance. The dose o f chloroquine needed to to ta lly inhibit oxytocin-induced contractions o f rat uterine smooth muscles was 4ng. 'Ibis was equivalent to both concentration o f 200pg/ml. f ) Chloroquine may exert its alleged abortifacient action by causing sudden changes in intrauterine pressure. Due to its well known tox ic ity , caution is urged in the use of chloroquine than i t is at present and reconsideration o f the proposed chloroquinization of sa lt to counter malaria mena ce in developing countries is suggested before implementation.