PHARMACOLOGY OF M & B 18,706, A DRUG WHICH SELECTIVELY REDUCES DECEREBRATE RIGIDITY

Abstract

(±)‐10‐(3‐Dimethylamino‐2‐methylpropyl)‐2‐valeroylphenothiazine hydrochloride (M & B 18,706) has been compared with dimethothiazine, chlorpromazine, diazepam and baclofen for potency in reducing decerebrate rigidity in the cat and rat and for activity in causing ataxia or sedation. 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. 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. 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. M & B 18,706 had intravenous potency comparable to chlorpromazine in reducing the pressor action of noradrenaline in the spinal cat.

A Comparison of the Actions of Some Drugs on Decerebrate Rigidity, Muscle Spindle Activity and Α‐adrenoceptors

“…Furthermore, dimethothiazine, chlorpromazine (Maxwell & Read, 1972) and M & B 18,706 (Maxwell et al, 1974) have less than one-tenth the potency in reducing the rigidity of cats decerebrated by the ischaemic method than they do in reducing intercollicular decerebrate rigidity. The rigidity of cats decerebrated by the ischaemic method is not due to enhanced activity of fusimotor neurones (Granit, 1970).…”

“…The method used to measure the degree of decerebrate rigidity and its reduction by drugs was that described by Maxwell & Read (1972) and Maxwell, Read & Sumpter (1974). The electromyogram (EMG) of the quadriceps muscle was recorded and integrated whilst that muscle was slowly stretched by the weight of the lower leg.…”