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British Journal of Pharmacology and Chemotherapy logoLink to British Journal of Pharmacology and Chemotherapy
. 1964 Apr;22(2):301–317. doi: 10.1111/j.1476-5381.1964.tb02035.x

Some pharmacological properties of thioproperazine and their modification by anti-parkinsonian drugs

G B Leslie, D R Maxwell
PMCID: PMC1703976  PMID: 14190465

Abstract

The pharmacological properties of a phenothiazine derivative thioproperazine have been compared with those of chlorpromazine, and the modifications by some anti-Parkinsonian 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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ASKEW B. M. Hyperpyrexia as a contributory factor in the toxicity of amphetamine to aggregated mice. Br J Pharmacol Chemother. 1962 Oct;19:245–257. doi: 10.1111/j.1476-5381.1962.tb01186.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BOYD E. M., CASSELL W. A. Agents affecting apomorphine-induced vomiting. J Pharmacol Exp Ther. 1957 Mar;119(3):390–394. [PubMed] [Google Scholar]
  3. BRAND E. D., HARRIS T. D., BORISON H. L., GOODMAN L. S. The anti-emetic activity of 10-(gamma-dimethylaminopropyl)-2-chlorophenothiazine (chlorpromazine) in dog and cat. J Pharmacol Exp Ther. 1954 Jan;110(1):86–92. [PubMed] [Google Scholar]
  4. BURN J. H., HOBBS R. A test for tranquillizing drugs. Arch Int Pharmacodyn Ther. 1958 Jan 1;113(3-4):290–295. [PubMed] [Google Scholar]
  5. DE SALVA S. J., OESTER Y. T. The effect of central depressants on certain spinal reflexes in the acute high cervical cat. Arch Int Pharmacodyn Ther. 1960 Feb 1;124:255–262. [PubMed] [Google Scholar]
  6. DELAY J., DENIKER P., ROBERT R., BEEK H., BARANDE R., EURIEULT M. Syndromes neurologiques expérimentaux et thérapeutique psychiatrique. I. Effets neurologiques d'un nouveau neuroleptique majeur, le 7843 RP. Presse Med. 1959 Jan 24;67(4):123–126. [PubMed] [Google Scholar]
  7. DENHAM J., CARICK D. J. Therapeutic value of thioproperazine and the importance of the associated neurological disturbances. J Ment Sci. 1961 Mar;107:326–345. doi: 10.1192/bjp.107.447.326. [DOI] [PubMed] [Google Scholar]
  8. DEWS P. B. The measurement of the influence of drugs on voluntary activity in mice. Br J Pharmacol Chemother. 1953 Mar;8(1):46–48. doi: 10.1111/j.1476-5381.1953.tb00749.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DOMINO E. F. Human pharmacology of tranquilizing drugs. Clin Pharmacol Ther. 1962 Sep-Oct;3:599–664. doi: 10.1002/cpt196235599. [DOI] [PubMed] [Google Scholar]
  10. EHRINGER H., HORNYKIEWICZ O. [Distribution of noradrenaline and dopamine (3-hydroxytyramine) in the human brain and their behavior in diseases of the extrapyramidal system]. Klin Wochenschr. 1960 Dec 15;38:1236–1239. doi: 10.1007/BF01485901. [DOI] [PubMed] [Google Scholar]
  11. FINK G. B., LARSON R. E. Some determinants of amphetamine toxicity in aggregated mice. J Pharmacol Exp Ther. 1962 Sep;137:361–364. [PubMed] [Google Scholar]
  12. FRIEND D. G. Modern diuretics and diuretic therapy. Clin Pharmacol Ther. 1960 Mar-Apr;1:5–11. doi: 10.1002/cpt196012v. [DOI] [PubMed] [Google Scholar]
  13. Gaddum J. H. A method of recording the respiration. J Physiol. 1941 Jan 14;99(2):257–264. doi: 10.1113/jphysiol.1941.sp003899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. HIEBEL G., BONVALLET M., DELL P. Action de la chlorpromazine (Largactil 45 60 RP) au niveau du système nerveux central. Sem Hop. 1954 Jun 6;30(37):2346–2353. [PubMed] [Google Scholar]
  15. HOEHN R., LASAGNA L. Effects of aggregation and temperature on amphetamine toxicity in mice. Psychopharmacologia. 1960 Feb 12;1:210–220. doi: 10.1007/BF00402742. [DOI] [PubMed] [Google Scholar]
  16. KLINE N. S., METTLER F. A. The extrapyramidal system and schizophrenia. Rev Can Biol. 1961 Jun;20:583–587. [PubMed] [Google Scholar]
  17. LAMBERT P. A., COURVOISIER S., JULOU L. [3-(1-methylsulfonyl-4-piperazino)-propyl] phenothiazine (R.P. 9.260)]. Psychopharmacologia. 1961;2:209–213. doi: 10.1007/BF00407981. [DOI] [PubMed] [Google Scholar]
  18. LASAGNA L., DEKORNFELD T. J. Methotrimeprazine: a new phenothiazine derivative with analgesic properties. JAMA. 1961 Dec 2;178:887–890. doi: 10.1001/jama.1961.03040480017004. [DOI] [PubMed] [Google Scholar]
  19. LASAGNA L., MCCANN W. P. Effect of tranquilizing drugs on amphetamine toxicity in aggregated mice. Science. 1957 Jun 21;125(3260):1241–1242. doi: 10.1126/science.125.3260.1241. [DOI] [PubMed] [Google Scholar]
  20. LEITCH A., CULLEN W., ROBERTSON D. The treatment of mania by thioproperazine (Majeptil). A preliminary report. Psychopharmacologia. 1962 Oct 5;3:307–315. doi: 10.1007/BF00411371. [DOI] [PubMed] [Google Scholar]
  21. LINGJAERDE O. CLINICAL EXPERIENCES WITH THIOPROPERAZINE ("MAJEPTIL") IN CHRONIC SCHIZOPHRENIA, PSYCHOTIC EXCITATION, AND SENILE AGITATION. Psychopharmacologia. 1963 May 21;4:281–293. doi: 10.1007/BF00408183. [DOI] [PubMed] [Google Scholar]
  22. MARTIN W. R., DEMAAR E. W., UNNA K. R. Chlorpromazine. I. The action of chlorpromazine and related phenothiazines on the EEG and its activation. J Pharmacol Exp Ther. 1958 Mar;122(3):343–358. [PubMed] [Google Scholar]
  23. MAXWELL D. R., PALMER H. T., RYALL R. W. A comparison of the analgesic and some other central properties of methotrimeprazine and morphine. Arch Int Pharmacodyn Ther. 1961 Jun 1;132:60–73. [PubMed] [Google Scholar]
  24. MORPURGO C. Effects of antiparkinson drugs on a phenothiazine-induced catatonic reaction. Arch Int Pharmacodyn Ther. 1962 May 1;137:84–90. [PubMed] [Google Scholar]
  25. ROTHBALLER A. B. The effects of catecholamines on the central nervous system. Pharmacol Rev. 1959 Jun;11(2 Pt 2):494–547. [PubMed] [Google Scholar]
  26. SCHENKER E., HERBST H. PHENOTHIAZINE UND AZAPHENOTHIAZINE ALS HEILMITTEL. Fortschr Arzneimittelforsch. 1963;5:269–627. [PubMed] [Google Scholar]
  27. SU C., LEE C. Y. The mode of neuromuscular blocking action of chlorpromazine. Br J Pharmacol Chemother. 1960 Mar;15:88–94. doi: 10.1111/j.1476-5381.1960.tb01214.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. SWINYARD E. A., CLARK L. D., MIYAHARA J. T., WOLF H. H. Studies on the mechanism of amphetamine toxicity in aggregated mice. J Pharmacol Exp Ther. 1961 Apr;132:97–102. [PubMed] [Google Scholar]
  29. Schweitzer A., Wright S. Effects on the knee jerk of stimulation of the central end of the vagus and of various changes in the circulation and respiration. J Physiol. 1937 Jan 18;88(4):459–475. doi: 10.1113/jphysiol.1937.sp003453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. TEDESCHI D. H., TEDESCHI R. E., FELLOWS E. J. Central serotonin antagonist activity of a number of phenothiazines. Arch Int Pharmacodyn Ther. 1961 Jun 1;132:172–179. [PubMed] [Google Scholar]
  31. WIRTH W., GOSSWALD R., HORLEIN U., RISSE K. H., KREISKOTT H. Zur Pharmakologie acylierter Phenothiazin-Derivate. Arch Int Pharmacodyn Ther. 1958 May 1;115(1-2):1–31. [PubMed] [Google Scholar]

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