Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1969 Sep;37(1):94–103. doi: 10.1111/j.1476-5381.1969.tb09526.x

Blockade of biogenic amine synthesis

Its effect on the responses to Leptazol and dexamphetamine in rats

P S J Spencer, T A R Turner
PMCID: PMC1703769  PMID: 5343360

Abstract

1. The convulsive effects of leptazol in the rat are potentiated by prior treatment with dexamphetamine.

2. An intact dopamine synthesis is necessary for the potentiation of the convulsive action of leptazol.

3. An intact noradrenaline synthesis is not necessary for this action of amphetamine, as long as the dopamine synthesis is intact.

4. An intact 5-hydroxytryptamine synthesis is not necessary for the potentiation to be shown.

5. Blockade of either noradrenaline, dopamine or 5-hydroxytryptamine synthesis has no direct effect on leptazol convulsions.

6. It is possible that it is an intact 3-4 dihydroxyphenylalanine (dopa) synthesis rather than an intact dopamine synthesis that is involved.

Full text

PDF
96

Selected References

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

  1. BERTLER A., CARLSSON A., ROSENGREN E. A method for the fluorimetric determination of adrenaline and noradrenaline in tissues. Acta Physiol Scand. 1958 Dec 15;44(3-4):273–292. doi: 10.1111/j.1748-1716.1958.tb01627.x. [DOI] [PubMed] [Google Scholar]
  2. CARLSSON A., LINDQVIST M. In-vivo decarboxylation of alpha-methyl DOPA and alpha-methyl metatyrosine. Acta Physiol Scand. 1962 Jan;54:87–94. doi: 10.1111/j.1748-1716.1962.tb02331.x. [DOI] [PubMed] [Google Scholar]
  3. CARLSSON A., WALDECK B. A fluorimetric method for the determination of dopamine (3-hydroxytyramine). Acta Physiol Scand. 1958 Dec 15;44(3-4):293–298. doi: 10.1111/j.1748-1716.1958.tb01628.x. [DOI] [PubMed] [Google Scholar]
  4. Carlsson A., Fuxe K., Hökfelt T. Failure of dopamine to accumulate in central noradrenaline neurons after depletion with diethyldithiocarbamate. J Pharm Pharmacol. 1967 Jul;19(7):481–483. doi: 10.1111/j.2042-7158.1967.tb08116.x. [DOI] [PubMed] [Google Scholar]
  5. Carlsson A., Lindqvist M., Fuxe K., Hökfelt T. Histochemical amd biochemical effects of diethyldithiocarbamate on tissue catecholamines. J Pharm Pharmacol. 1966 Jan;18(1):60–62. doi: 10.1111/j.2042-7158.1966.tb07773.x. [DOI] [PubMed] [Google Scholar]
  6. DAY M. D., RAND M. J. A hypothesis for the mode of action of alpha-methyldopa in relieving hypertension. J Pharm Pharmacol. 1963 Apr;15:221–224. doi: 10.1111/j.2042-7158.1963.tb12778.x. [DOI] [PubMed] [Google Scholar]
  7. DAY M. D., RAND M. J. SOME OBSERVATIONS ON THE PHARMACOLOGY OF ALPHA-METHYLDOPA. Br J Pharmacol Chemother. 1964 Feb;22:72–86. doi: 10.1111/j.1476-5381.1964.tb01545.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Day M. D., Rand M. J. Mode of action of methyldopa. J Pharm Pharmacol. 1967 Jun;19(6):395–396. doi: 10.1111/j.2042-7158.1967.tb09566.x. [DOI] [PubMed] [Google Scholar]
  9. Dingell J. V., Owens M. L., Norvich M. R., Sulser F. On the role of norepinephrine biosynthesis in the central action of amphetamine. Life Sci. 1967 Jun 1;6(11):1155–1162. doi: 10.1016/0024-3205(67)90197-x. [DOI] [PubMed] [Google Scholar]
  10. FRIEBEL H., KLATT I. Zur Prüfung der antikonvulsiven Wirkung von Arzneimitteln mit dem Pentamethylentetrazol-Krampf-Test. Arzneimittelforschung. 1959 Apr;9(4):245–247. [PubMed] [Google Scholar]
  11. FULLER R. W., HINES C. W., MILLS J. LOWERING OF BRAIN SEROTONIN LEVEL BY CHLORAMPHETAMINES. Biochem Pharmacol. 1965 Apr;14:483–488. doi: 10.1016/0006-2952(65)90221-2. [DOI] [PubMed] [Google Scholar]
  12. Frey H. H., Magnussen M. P. Different central mediation of the stimulant effects of amphetamine and its p-chloro analogue. Biochem Pharmacol. 1968 Jul;17(7):1299–1307. doi: 10.1016/0006-2952(68)90067-1. [DOI] [PubMed] [Google Scholar]
  13. Gerst E. C., Steinsland O. S., Walcott W. W. Use of constant temperature and sodium borohydride in the trihydroxyindole method for catecholamines. Cancer Res. 1966 Oct;12(11 Pt 2):659–669. [PubMed] [Google Scholar]
  14. Goldstein M. Inhibition of norepinephrine biosynthesis at the dopamine-beta-hydroxylation stage. Pharmacol Rev. 1966 Mar;18(1):77–82. [PubMed] [Google Scholar]
  15. HESS S. M., CONNAMACHER R. H., OZAKI M., UDENFRIEND S. The effects of alpha-methyl-DOPA and alpha-methyl-metatyrosine on the metabolism of norepinephrine and serotonin in vivo. J Pharmacol Exp Ther. 1961 Nov;134:129–138. [PubMed] [Google Scholar]
  16. Hanson L. C. Evidence that the CCENTRAL ACTION OF (+)-amphetamine is mediated via catecholamines. Psychopharmacologia. 1967;10(4):289–297. doi: 10.1007/BF00403897. [DOI] [PubMed] [Google Scholar]
  17. Hashimoto Y., Ohi Y., Imaizumi R. Inhibition of brain dopamine beta-oxidase in vivo by disulfiram. Jpn J Pharmacol. 1965 Dec;15(4):445–446. doi: 10.1254/jjp.15.445. [DOI] [PubMed] [Google Scholar]
  18. Koe B. K., Weissman A. p-Chlorophenylalanine: a specific depletor of brain serotonin. J Pharmacol Exp Ther. 1966 Dec;154(3):499–516. [PubMed] [Google Scholar]
  19. LIPPMANN W., WISHNICK M. EFFECT OF DL-P-CHLORO-N-METHYLAMPHETAMINE ON THE CONCENTRATIONS OF MONOAMINES IN THE CAT AND RAT BRAIN AND RAT HEART. Life Sci. 1965 Apr;4:849–857. doi: 10.1016/0024-3205(65)90279-1. [DOI] [PubMed] [Google Scholar]
  20. PLETSCHER A., BURKARD W. P., BRUDERER H., GEY K. F. DECREASE OF CEREBRAL 5-HYDROXYTRYPTAMINE AND 5-HYDROXYINDOLACETIC ACID BY AN ARYLALKYLAMINE. Life Sci. 1963 Nov;11:828–833. doi: 10.1016/0024-3205(63)90094-8. [DOI] [PubMed] [Google Scholar]
  21. PLETSCHER A., BURKARD W. P., GEY K. F. EFFECT OF MONOAMINE RELEASERS AND DECARBOXYLASE INHIBITORS ON ENDOGENOUS 5-HYDROXYINDOLE DERIVATIVES IN BRAIN. Biochem Pharmacol. 1964 Mar;13:385–390. doi: 10.1016/0006-2952(64)90156-x. [DOI] [PubMed] [Google Scholar]
  22. Randrup A., Munkvad I. Brain dopamine and amphetamine-induced stereotyped behaviour. Acta Pharmacol Toxicol (Copenh) 1967;25(Suppl):62–62. doi: 10.1111/j.1600-0773.1967.tb03049.x. [DOI] [PubMed] [Google Scholar]
  23. SPECTOR S., SJOERDSMA A., UDENFRIEND S. BLOCKADE OF ENDOGENOUS NOREPINEPHRINE SYNTHESIS BY ALPHA-METHYL-TYROSINE, AN INHIBITOR OF TYROSINE HYDROXYLASE. J Pharmacol Exp Ther. 1965 Jan;147:86–95. [PubMed] [Google Scholar]
  24. Scheel-Krüger J., Randrup A. Production of a stereotyped behaviour in rats by dopamine in the absence of noradrenaline. Acta Pharmacol Toxicol (Copenh) 1967;25(Suppl):61–61. doi: 10.1111/j.1600-0773.1967.tb03048.x. [DOI] [PubMed] [Google Scholar]
  25. Sulser F., Owens M. L., Norvich M. R., Dingell J. V. The relative role of storage and synthesis of brain norepinephrine in the psychomotor stimulation evoked by amphetamine or by desipramine and tetrabenazine. Psychopharmacologia. 1968;12(4):322–332. doi: 10.1007/BF00401410. [DOI] [PubMed] [Google Scholar]
  26. Turner T. A., Spencer P. S. Effect of pretreatment with monoamine oxidase inhibitors or (+)-amphetamine on leptazol convulsions in mice and rats. J Pharm Pharmacol. 1968 Dec;20(Suppl):122S+–122S+. doi: 10.1111/j.2042-7158.1968.tb09872.x. [DOI] [PubMed] [Google Scholar]
  27. VON EULER U. S., FLODING I. A fluorimetric micromethod for differential estimation of adrenaline and noradrenaline. Acta Physiol Scand Suppl. 1955;33(118):45–56. [PubMed] [Google Scholar]
  28. Weissman A., Koe B. K. Contrasting locomotor effects of catecholamine releasers and tyrosine hydroxylase inhibitors in MAO-inhibited mice. Psychopharmacologia. 1967 Aug 4;11(3):282–286. doi: 10.1007/BF00405235. [DOI] [PubMed] [Google Scholar]
  29. Weissman A., Koe B. K., Tenen S. S. Antiamphetamine effects following inhibition of tyrosine hydroxylase. J Pharmacol Exp Ther. 1966 Mar;151(3):339–352. [PubMed] [Google Scholar]
  30. van ROSSUM J., van der SCHOOT J., HURKMANS J. A. Mechanism of action of cocaine and amphetamine in the brain. Experientia. 1962 May 15;18:229–231. doi: 10.1007/BF02148316. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES