Effects of Chlorpromazine on Cerebral Circulation and Electroencephalogram in Cats

Abstract

In several recent experimental and clinical studies the action of chlorpromazine (2-chloro-10-[3-dimethylaminopropyl] phenothiazine hydrochloride) upon central nervous structures has been studied. Thus, Laborit and Hugu\l=e'\nard 10 demonstrated its general sedative action, and Courvoisier et al.2 reported several effects of the drug which were due to its central depressing action, e. g., its vasodilating, muscle-relaxant, and antiemetic properties. Both groups also pointed out that chlorpromazine potentiated anesthesia. Dobkin et al.,3 furthermore, have shown that it depresses reflexes elicited from the respiratory tract. Terzian 17 and Hiebel et al.6 studied the effects of chlorpromazine upon the EEG. They found that the drug induced a synchronized pattern with slow waves and spindles, due to its depressing action upon the reticular activating system of the brain stem. Similar results have been obtained by Turner et al.18 and others in clinical studies.Chlorpromazine has also been used as a muscle-relaxant in motor disorders and psychic states characterized by spasticity or tension ( Lehmann and Haurahan12 and Basmajian and Szatmarix).( Reservationsanslaget). through an influence upon the reticular system of the brain stem. This action of the drug may be of significance for the explanation of its effect upon the muscle tone.The present study was carried out with a new method of recording the cerebral blood flow (Ingvar and Söderberg8), by which it has been demonstrated that general changes in the EEG may be accompanied by changes of the cerebral vascular resistance (Ing¬ var7; Ingvar and Söderberg*). It has now been found that chlorpromazine in the lightly anesthetized preparation reduces the cerebral vascular resistance and that spindles and slow waves at the same time may appear in the EEG. MethodThe method, which is described in detail else¬ where (Ingvar and Söderberg"), measures the out¬ flow from the cannulated superior sagittal sinus (after elimination of diploic anastomoses) by an electric drop recorder. Preparations under pentobarbital (Nembutal) or thiopental (Penthothal) anesthesia or of the encéphale or cerveau isolé type (prepared under ether, followed by thio¬ pental) were used. The EEG was recorded with bipolar leads from rostral parts of the brain.The blood pressure was measured in the femoral artery with an electromanometer. Chlorpromazine* was slowly administered intravenously in a 0.5% solution (usually in doses of 1 mg. per kilogram) or intra-arterially, in the carotid artery. The ear skin temperature was measured as an index of cutaneous blood flow. ResultsIn the lightly anesthetized animal with intact brain stem chlorpromazine was found to reduce the cerebral vascular resistance.