The Effect Of Chloroquine On The Smooth Cardiac And Skeletal Muscles: A Re-Evaluation

Abstract

The effect 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 all cases, isolated tissues were used. In addition, the effect of intraperitoneal (IP) administration of 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 effect of acetylcholine (Ach), histamine, nicotine and barium chloride on the guinea pig trachoal smooth muscles. b) Causes short-lived relaxation of rabbit ileal 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 effects on the isolated rabbit heart and opposes the positive chronotropic responses due to adrenaline and isoprenaline probably by pi- adrenergic blocking activity. j.t also antqg&izes the cardiostimulant action of caffeine and barium chloride. “Hie negative chronotropic action could oe the basis of its well known antiarrhythmie property, d ' In addition to causing depression of neuromuscular transmission, chloroquine potentiates the neuromuscular blocking effect of tubocurarine succinylcholine andlignocaLne probably by a non—specific interference with ionic conductance. - 2 - e) Chloroquine has no uterotonic activity 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 of chloroquine needed to totally inhibit oxytocin-induced contractions of rat uterine smooth muscles was 4ng. 'Ibis was equivalent to both concentration of 200pg/ml. f) Chloroquine may exert its alleged abortifacient action by causing sudden changes in intrauterine pressure. Due to its well known toxicity, caution is urged in the use of chloroquine than it is at present and reconsideration of the proposed chloroquinization of salt to counter malaria mena ce in developing countries is suggested before implementation. KEY WORDS . Antagonism . Potentiation .$ inbitition • Relaxation • Contraction . Antiasthiratic .Antiadrenergic . Antiarrhythmic *.Membrane stabilization . Ionic conductance .Intrauteri-ne pressure