A New Chemical Structure with Specific Depressant Effects on the Amygdala and on the Hyper-irritability of the ‘Septal Rat’

Abstract

THE compound, 5-(2-dimethylaminoethyl)-2,3-dihydro-2-phenyl-l,5-benzothiazepin-4(5H)-one hydrochloride (SQ 10,496), was synthesized in our laboratories by Dr. John Krapcho¹. This compound had no striking effects in normal laboratory animals; but its apparent specificity in antagonizing the hyper-irritability exhibited by rats with bilateral lesions of the septal area (‘septal rats’)² aroused our interest. The behavioural abnormalities (exaggerated reactions to a puff of air, to the approach of a probe or glove, and to handling) of the ‘septal rats’ were scored at various times following drug injections and the per cent decrease in irritability calculated by comparing post-drug scores to pre-drug scores (usually one hour). The median effective doses (ED₅₀'s) for reducing the scores were determined for chlorpromazine hydrochloride, chlordiazepoxide hydrochloride, pentobarbital sodium and SQ 10,496 after their intraperitoneal injection.