TRANQUILLIZING AND HYPOTENSIVE ACTIVITIES OF TWELVE PHENOTHIAZINES.

Twelve phenothiazine derivatives have been compared in relation to their central sedative, tranquillizing and hypotensive activities. The ED50's of the compounds to suppress the conditioned response, unconditioned response and forced locomotor activity were determined. Suppressions of the conditioned and unconditioned responses were taken as criteria for tranquillizing and central sedative activities respectively. The "tranquillizing ratio" (ED50 for unconditioned response/ED50 for conditioned response) was used as the criterion of tranquillizing activity in relation to sedative activity and for purposes of comparison this ratio was assigned a value of unity for chlorpromazine. Perphenazine was the most potent drug in suppressing the conditioned and unconditioned responses whereas fluopromazine had the maximal "tranquillizing index" activity. Six compounds had great, three moderate and three mild hypotensive activity when doses of 1 mg/kg were injected intravenously into dogs. The relationship of the chemical structure to the central sedative activity is discussed.