Pharmacology of M & B 18,706, a drug which selectively reduces decerebrate rigidity

Abstract

1 (+/-)-10-(3-Dimethylamino-2-methylpropyl)-2-valeroylphenothiazine hydrochloride (M & B 18,706) has been compared with dimethothiazine, chloropromazine, diazepam and baclofen for potency in reducing decerebrate rigidity in the cat and rat and for activity in causing ataxia or sedation.2 When given intravenously M & B 18,706 had seven times the potency of dimethothiazine and one-half the potency of chlorpromazine in reducing the rigidity of the intercollicular decerebrate cat. When administered orally M & B 18,706 and chlorpromazine were equi-potent in reducing rigidity but M & B 18,706 was less effective than chlorpromazine in producing ataxia in this species.3 In the rat, M & B 18,706 had one-quarter the potency of chlorpromazine for reducing decerebrate rigidity but had from 1/20th to 1/200th its potency in tests for sedative or tranquillizing activity.4 M & B 18,706, like dimethothiazine and chlorpromazine, had little effect on the rigidity of ischaemic decerebrate cats and failed to inhibit polysynaptic spinal reflexes.5 M & B 18,706 had intravenous potency comparable to chlorpromazine in reducing the pressor action of noradrenaline in the spinal cat.