Some Pharmacological Properties of Thioproperazine and Their Modification by Anti‐parkinsonian Drugs

Abstract

The pharmacological properties of a phenothiazine derivative thioproperazine have been compared with those of chlorpromazine, and the modifications by some antiParkinsonian drugs of its actions on the central nervous system have been studied.Thioproperazine was less potent than chlorpromazine in lowering blood pressure and antagonizing adrenaline in the cat, in depressing respiratory rate in the rabbit, in producing hypothermia and analgesia and in reducing the minimum anaesthetic dose of hexobarbitone in mice, and in protecting rats from convulsions induced by tryptamine. It was roughly equipotent to chlorpromazine in reducing locomotor activity of mice. Thioproperazine was more potent than chlorpromazine in protecting grouped mice from the acute toxicity of dexamphetamine, in preventing the acute behavioural disturbances produced by dexamphetamine in the rat, in producing a state of experimental catatonia in the rat and in preventing the emetic action of apomorphine in the dog. Hyoscine, benztropine or promethazine greatly reduced the ability of thioproperazine to prevent behavioural changes due to dexamphetamine in the rat and also abolished symptoms of experimental catatonia produced by thioproperazine. In contrast, the antiapomorphine activity of thioproperazine in the dog was not reduced to any extent by hyoscine or benztropine.

Central Effects of Anticholinergic Drugs Measured by the Apomorphine Gnawing Test in Mice

“…This result agrees with other published evidence which has revealed that anticholinergic drugs antagonize several behavioural effects considered to be highly characteristic for neuroleptic drugs: catalepsy and antiamphetamine actions of neuroleptics (MORPURGO 1962;MORPURGO & THEOBALD 1964;LESLIE & MAXWELL 1964). PEDERSEN (1967) found that a small dose of flupentixol (a very potent neuroleptic drug) was without significant effect against the gnawing in mice induced by apomorphine in combination with anticholinergics.…”

Interaction between some anticholinergic agents and phenothiazines: Potentiation of phenothiazine sedation and its antagonism

“…<) These findings in man must also be reviewed in the light of other studies in different animal species which appear at variance with the findings reported here. In man, the anticholinergic agents and the phenothiazine compounds induce a marked potentiation of central nervous system depreSSion, whereas it would appear that in studies with rats o BroWll, M. L.: Personal communication, 1965. an antagonistic action between these groups of drugs has been reported 14 and a similar antagonistic effect has been seen by others. 12,15 Anticholinesterase agents have been found to potentiate CPZ-induced behavioral changes in rats by increasing the disruption of aVOidance-responding in these animals.…”

Modification by Drugs of the Metabolism of 3,4‐dihydroxyphenylethylamine, Noradrenaline and 5‐hydroxytryptamine in the Brain

“…The phenothiazine derivatives selected for examination were chlorpromazine, trifluoperazine, which causes a high incidence of Parkinsonian side-effects in man (Ayd, 1961), thioridazine, for which a low incidence of these side-effects has been reported (Cole & Clyde, 1961), and thioproperazine, which has a potent catatonic action in rats (Leslie & Maxwell, 1964). Chlorpromazine has been reported to increase the acid metabolites of dopamine in the brain of the rabbit (Anden et al, 1964).…”