EMESIS INDUCED BY THE INTRACEREBROVENTRICULAR ADMINISTRATION OF HYDERGINE AND MECHLORETHAMINE HYDROCHLORIDE

¹ Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York

A cannula was aseptically implanted in the lateral, third or fourth ventricle of dogs and, after recovery, Hydergine or mechlorethamine was injected into these cerebral ventricles to induce emesis. With Hydergine, the ED5O was 0.55 µg for the lateral, 0.15 µg for the third and 0.02 µg for the fourth ventricle. The corresponding geometric mean latencies were 19.0, 12.0 and 7.7 min respectively. Statistical analyses of these values showed that both the dosage and latency for one ventricular route were significantly different from those for another. Furthermore, in four dogs with chemoceptive trigger-zone ablation, emesis was not obtained with as much as 20 to 100 times the ED50 for the fourth ventricle route. With mechlorethamine, the ED50's could not be accurately determined. They were approximately 750, 320 and 113 µg for the lateral, third and fourth ventricles respectively. In three dogs with chemoceptive trigger-zone ablation, emesis was not observed at doses 9 or more times the estimated ED50 for the fourth ventricle route. Perphenazine, 0.1 mg/kg i.v., was found to be effective, while chlorpromazine, 2.0 mg/kg i.v., was not effective in preventing emesis induced by moderately large doses of mechlorethamine injected into the fourth ventricle.