The pharmacological actions of chlorpromazine have been described in detail by Courvoisier, Fournel, Ducrot, Kolsky, and Koetschet (1953). This substance was introduced into anaesthetic practice by Laborit and Huguenard (1951) and is given together with promethazine and pethidine, so that it is impossible to know what contribution each makes to the joint effect. We have therefore compared their pharmacological properties quantitatively as well as qualitatively.The properties tested were the power to reduce body temperature; the effect on skeletal muscle stimulated directly and through the nerve; the chronic toxicity; the power to potentiate (a) pentobarbitone, (b) morphine; the anti-adrenaline action; the anti-acetylcholine action; the antihistamine action; and the local anaesthetic action. METHODS Body TemperatureEight male mice were used in each experiment, their rectal temperatures being recorded by inserting a lubricated thermocouple into the rectum. This thermocouple was connected to a moving coil galvanometer and the cold junction thermocouple was placed in a constantly stirred water bath at 250 C. The mice were held in position by fastening the tail with adhesive tape to one end of a wire and turning the other end into a loop round the chest. Each mouse was placed in a small celluloid cage of hemispherical cross-section. After half an hour to an hour their temperatures remained steady, and then four mice were used as controls and were injected with saline, while the other four were injected with the substance being tested. The mean difference in temperature between the two groups of mice before the injections was taken as zero and allowance was always made for this difference in calculating the mean temperature-difference between the test mice and the controls recorded at 15-min. intervals. Skeletal MuscleThe sciatic-gastrocnemius preparation of the cat was used as described by Dale and Gasser (1926). The muscle was stimulated indirectly through the sciatic nerve by rectangular voltage pulses and directly through the muscle by means of induction shocks from a Lewis rotary contact breaker. The rates of stimulation were adjusted so that they were both about 8 or 9/min., and the muscle was continuously stimulated by each method alternately at 1 min. intervals. Injections were made into the right iliac artery close to the bifurcation of the abdominal aorta.The phrenic nerve-diaphragm preparation of the rat was also used. The experimental procedure was the same as that described by Bfilbring (1946), the nerve being stimulated by a pair of platinum electrodes submerged in the organ bath (50 ml.). Anti-adrenaline ActionThe anti-adrenaline actions of chlorpromazine, promethazine and pethidine were compared on three preparations-the vessels of the rabbit ear, the blood pressure of the spinal cat, and the smooth muscle of the rabbit uterus.(a) Vessels of Rabbit Ear.-The central artery of the rabbit ear was cannulated and injections were made into it by means of the device described by Gaddum and Kwiatkowski (1938)...
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