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Title: Studies on the pharmacology of some antimalarial drugs
Author: Ojewole, J. A. O.
ISNI:       0000 0001 3455 6478
Awarding Body: University of Strathclyde
Current Institution: University of Strathclyde
Date of Award: 1976
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Pharmacological studies of the antimalarial drugs chloroquine, primaquine, quinine, progtianil and pyrimethamine have been made. These studies have shown that the compounds possess a wide spectrum of pharmacological actions in common on many tissues and organ-systems. In most cases, their effects were biphasic, consisting of an initial stimulation followed by a more permanent inhibitory phase. All five antimalarial compounds, at low concentrations, reduced the base-line tone (tension) of all smooth muscles studied, and augmented electrically-induced contractions of the chick oesophagus, vas deferens and central ear artery preparations. Higher concentrations of the drugs dose-dependently contracted gastrointestinal smooth muscles and inhibited the spontaneous, myogenic rhythmic contractions of intestinal muscles, uterine strips and portal veins in vitro in a dose-dependent manner. In the same dose range they inhibited the electrically-evoked contractions of the chick oesophagus, vas deferens and central ear artery preparations. The drugs relaxed tracheal chain preparations contracted with acetylcholine (in the presence of physostigmine), carbachol, histamine and 5-hydroxytryptamine. In vitro, all five compounds antagonised the actions of standard spasmogens in all preparations examined. This spasmolytic effect of the drugs has been shown to be non-specific in nature. All the five compounds, in very low dosos, augmented the action of acetylcholine on frog rectus abdominis and chick biventer-cervicis muscles. High concentrations of the drugs themselves caused dose-related sustained contractions of the muscles in vitro. In similar concentrations they inhibited, or abolished, the actions of acetylcholine, carbachol, nicotine and potassium chloride. In some cases, low concentrations of the compounds, especially quinine, chloroquine and primaquine, augmented electrically-induced twitches of the chick biventer and rat hemi-diaphragm muscles in vitro, and of the soleus and tibialis anterior muscles of the cat in vivo. High doses of the compounds, themselves inhibited the twitches in a dose-related manner, and augmented the effects of neuromuscular blocking agents on the preparations. The drugs also inhibited tho tetanic as well as the intra-arterially injected acetylcholine- induced contractions of the tibialis anterior muscle in vivo. All the five compounds possessed anticholinesterase activity. In isolated cardiac muscle, all the five drugs studied increased the refractory period and caused negative inotropic and chronotropic responses. However, low concentrations of the quinoline compounds (primaquine, chloroquine and quinine) induced slight but measurable transient positive inotropic and chronotropic affects in the heart. Intravenous injections of each of the five compounds into anaesthetized cats produced similar cardiovascular changes. Those changes consisted of dose-dependent reductions in systemic and pulmonary arterial pressures, left ventricular pressure, left ventricular dP/dt max; and heart rate. Other changes consisted of dose-related increases in right atrial and left ventricular, end-diastolic pressures, P-R interval and QRS complex duration. All the compounds inhibited or abolished the pressor effects of intravenous noradrenaline on the cardiovascular system.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral