SOME NEUROPHARMACOLOGICAL PROPERTIES OF THIORIDAZINE HYDROCHLORIDE (MELLARIL)

¹ Departments of Pharmacology, University of Utah College of Pharmacy and College of Medicine, Salt Lake City, Utah

Thioridazine hydrochloride (Mellaril, TP-21, 2-methylmercapto-10-[2'-(N-methyl-piperidyl- 2'')-ethyl-1'] phenothiazine hydrochloride) and chiorpromazine hydrochloride (Thorazine) have been examined for neuropharmacological properties in mice and rats by several standardized tests. Although thioridazine is less depressant than chlorpromazine when measured on the basis of minimal neurological deficit, the profiles of neurotoxicity of the 2 compounds are otherwise remarkably similar. Thioridazine and chlorpromazine exhibit a similar level of effectiveness as measured by ability to reduce amphet-amine toxicity in aggregated mice and to block a conditioned escape response in rats. Both drugs reduce spontaneous motor activity and low-frequency electroshock seizure thresholds in mice. Although both drugs lower body temperature and prolong hexobarbital sleep time in mice, chlorpromazine is more potent by these tests. In mice, both drugs are devoid of anticonvulsant activity, as measured by 5 tests, and neither drug significantly alters the intravenous pentylenetetrazol threshold or the maximal electroshock seizure latency, or completely prevents audiogenic seizures. The significance of these findings is discussed.