Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1971 Feb;41(2):198–212. doi: 10.1111/j.1476-5381.1971.tb08022.x

Some neurochemical effects of amphetamine, methylamphetamine and p-bromomethyl-amphetamine in the rat

B E Leonard, Susan A Shallice
PMCID: PMC1703283  PMID: 5572273

Abstract

1. Low doses of D-amphetamine increased brain noradrenaline concentrations in the rat; doses greater than 5 mg/kg, however, caused a decrease. Methylamphetamine also showed this dual effect, but a reduction in brain noradrenaline concentration only occurred when doses greater than 10 mg/kg were administered. p-Bromomethylamphetamine did not significantly reduce brain noradrenaline concentrations even at a dose of 60 mg/kg. The order of potency in reducing the concentration of noradrenaline correlated with the central stimulant effects; D-amphetamine produced the greatest and p-bromomethylamphetamine the least increase in motor activity.

2. D-Amphetamine and D-methylamphetamine potentiated the action of 4,α-dimethyl-m-tyramine (H77/77) in depleting brain noradrenaline; the greatest potentiation was produced by D-amphetamine. This suggests that the phenylethylamines may affect brain noradrenaline concentrations by acting on the reserpine resistant uptake mechanism.

3. Differences were found in the effect of the three drugs on brain dopamine concentrations; D-amphetamine caused a decrease while p-bromomethylamphetamine caused an increase. Methylamphetamine had no effect on the concentration of dopamine. Only p-bromomethylamphetamine significantly reduced the depletion of brain dopamine concentrations caused by H77/77.

4. Methylamphetamine and p-bromomethylamphetamine reduced the concentration of 5-hydroxytryptamine (5-HT) in the brain; administration of the same dose of D-amphetamine did not change the concentration of 5-HT.

5. Changes in the blood and brain concentrations of tyrosine and tryptophan, and in the concentration of γ-amino-n-butyric acid in the brain could not be correlated with the changes observed in the concentrations of biogenic amines in the brain.

Full text

PDF
198

Selected References

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

  1. BAIRD J. R., LEWIS J. J. THE EFFECTS OF COCAINE, AMPHETAMINE AND SOME AMPHETAMINE-LIKE COMPOUNDS ON THE IN VIVO LEVELS OF NORADRENALINE AND DOPAMINE IN THE RAT BRAIN. Biochem Pharmacol. 1964 Nov;13:1475–1482. doi: 10.1016/0006-2952(64)90197-2. [DOI] [PubMed] [Google Scholar]
  2. Carlsson A., Fuxe K., Hamberger B., Malmfors T. Effect of a new series of bicyclic compounds with potential thymoleptic properties on the reserpine-resistant uptake mechanism of central and peripheral monoamine neurones in vivo and in vitro. Br J Pharmacol. 1969 May;36(1):18–28. doi: 10.1111/j.1476-5381.1969.tb08299.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carlsson A., Lindqvist M., Dahlström A., Fuxe K., Masuoka D. Effects of the amphetamine group on intraneuronal brain amines in vivo and in vitro. J Pharm Pharmacol. 1965 Aug;17(8):521–523. doi: 10.1111/j.2042-7158.1965.tb07717.x. [DOI] [PubMed] [Google Scholar]
  4. Carlsson A., Waldeck B. Effects of amphetamine, tyramine, and protriptyline on reserpine-resistant amine-concentrating mechanisms of adrenergic nerves. J Pharm Pharmacol. 1966 Apr;18(4):252–253. doi: 10.1111/j.2042-7158.1966.tb07860.x. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. FULLER R. W., WALTERS C. P. INHIBITION OF MONOAMINE OXIDASE ACTION ON KYNURAMINE BY SUBSTRATE AMINES AND STEREOISOMERIC ALPHA-METHYL AMINES. Biochem Pharmacol. 1965 Feb;14:159–163. doi: 10.1016/0006-2952(65)90071-7. [DOI] [PubMed] [Google Scholar]
  7. GOLDSTEIN M., CONTRERA J. F. The inhibition of norepinephrine and epinephrine synthesis in vitro. Biochem Pharmacol. 1961 Jul;7:77–78. doi: 10.1016/0006-2952(61)90129-0. [DOI] [PubMed] [Google Scholar]
  8. GUROFF G., KING W., UNDENFRIEND S. The uptake of tyrosine by rat brain in vitro. J Biol Chem. 1961 Jun;236:1773–1777. [PubMed] [Google Scholar]
  9. HESS S. M., UDENFRIEND S. A fluorometric procedure for the measurement of tryptamine in tissues. J Pharmacol Exp Ther. 1959 Nov;127:175–177. [PubMed] [Google Scholar]
  10. 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]
  11. Häggendal J., Hamberger B. Quantitative in vitro studies on noradrenaline uptake and its inhibition by amphetamine, desipramine and chlorpromazine. Acta Physiol Scand. 1967 Jul-Aug;70(3):277–280. doi: 10.1111/j.1748-1716.1967.tb03626.x. [DOI] [PubMed] [Google Scholar]
  12. Knoll J., Vizi E. S., Ecseri Z. Psychomimetic methylamphetamine derivatives. Arch Int Pharmacodyn Ther. 1966 Feb;159(2):442–451. [PubMed] [Google Scholar]
  13. Leonard B. E., Tonge S. R. The effects of some hallucinogenic drugs upon the metabolism of noradrenaline. Life Sci. 1969 Aug 1;8(15):815–825. doi: 10.1016/0024-3205(69)90142-8. [DOI] [PubMed] [Google Scholar]
  14. Littleton J. M. The interaction of dexamphetamine with inhibitors of noradrenaline biosynthesis in rat brain in vivo. J Pharm Pharmacol. 1967 Jun;19(6):414–415. doi: 10.1111/j.2042-7158.1967.tb09575.x. [DOI] [PubMed] [Google Scholar]
  15. MCLEAN J. R., MCCARTNEY M. Effect of D-amphetamine on rat brain noradrenaline and serotonin. Proc Soc Exp Biol Med. 1961 May;107:77–79. doi: 10.3181/00379727-107-26540. [DOI] [PubMed] [Google Scholar]
  16. MOORE K. E., LARIVIERE E. W. EFFECTS OF D-AMPHETAMINE AND RESTRAINT ON THE CONTENT OF NOREPINEPHRINE AND DOPAMINE IN RAT BRAIN. Biochem Pharmacol. 1963 Nov;12:1283–1288. doi: 10.1016/0006-2952(63)90196-5. [DOI] [PubMed] [Google Scholar]
  17. MOORE K. E. THE ROLE OF ENDOGENOUS NOREPINEPHRINE IN THE TOXICITY OF D-AMPHETAMINE IN AGGREGATED MICE. J Pharmacol Exp Ther. 1964 Apr;144:45–51. [PubMed] [Google Scholar]
  18. MOORE K. E. TOXICITY AND CATECHOLAMINE RELEASING ACTIONS OF D- AND L-AMPHETAMINE IN ISOLATED AND AGGREGATED MICE. J Pharmacol Exp Ther. 1963 Oct;142:6–12. [PubMed] [Google Scholar]
  19. Miller F. P., Cox R. H., Jr, Snodgrass W. R., Maickel R. P. Comparative effects of p-chloroamphetamine and p-chloro-N-methylamphetamine on rat brain norepinephrine, serotonin and 5-hydroxyindole-3-acetic acid. Biochem Pharmacol. 1970 Feb;19(2):435–442. doi: 10.1016/0006-2952(70)90199-1. [DOI] [PubMed] [Google Scholar]
  20. Parmar S. S. Antagonism between stereoisomeric amphetamines, amphetamine derivatives and other monoamine oxidase inhibitors. Biochem Pharmacol. 1966 Oct;15(10):1497–1505. doi: 10.1016/0006-2952(66)90195-x. [DOI] [PubMed] [Google Scholar]
  21. Pletscher A., Da Prada M., Burkard W. P., Bartholini G., Steiner F. A., Bruderer H., Bigler F. Aralkylamines with different effects on the metabolism of aromatic monoamines. J Pharmacol Exp Ther. 1966 Oct;154(1):64–72. [PubMed] [Google Scholar]
  22. SMITH C. B. EFFECTS OF D-AMPHETAMINE UPON BRAIN AMINE CONTENT AND LOCOMOTOR ACTIVITY OF MICE. J Pharmacol Exp Ther. 1965 Jan;147:96–102. [PubMed] [Google Scholar]
  23. Schubert J., Nybäck H., Sedvall G. Effect of antidepressant drugs on accumulation and disappearance of monoamines formed in vivo from labelled precursors in mouse brain. J Pharm Pharmacol. 1970 Feb;22(2):136–139. doi: 10.1111/j.2042-7158.1970.tb08410.x. [DOI] [PubMed] [Google Scholar]
  24. Snyder S. H., Axelrod J., Zweig M. A sensitive and specific fluorescence assay for tissue serotonin. Biochem Pharmacol. 1965 May;14(5):831–835. doi: 10.1016/0006-2952(65)90102-4. [DOI] [PubMed] [Google Scholar]
  25. Tonge S. R., Leonard B. E. The effects of some hallucinogenic drugs upon the metabolism of 5-hydroxy-tryptamine in the brain. Life Sci. 1969 Aug 1;8(15):805–814. doi: 10.1016/0024-3205(69)90141-6. [DOI] [PubMed] [Google Scholar]
  26. UCHIDA T., O'BRIEN R. D. THE EFFECTS OF HYDRAZINES ON RAT BRAIN 5-HYDROXYTRYPTAMINE, NOREPINEPHRINE, AND GAMMA-AMINOBUTYRIC ACID. Biochem Pharmacol. 1964 May;13:725–730. doi: 10.1016/0006-2952(64)90008-5. [DOI] [PubMed] [Google Scholar]
  27. WAALKES T. P., UDENFRIEND S. A fluorometric method for the estimation of tyrosine in plasma and tissues. J Lab Clin Med. 1957 Nov;50(5):733–736. [PubMed] [Google Scholar]
  28. Weissman A., Koe B. K. Behavioral effects of L-alpha-methyltyrosine, an inhibitor of tyrosine hydroxylase. Life Sci. 1965 May;4(10):1037–1048. doi: 10.1016/0024-3205(65)90223-7. [DOI] [PubMed] [Google Scholar]
  29. Welch A. S., Welch B. L. Solvent extraction method for simultaneous determination of norepinephrine, dopamine, serotonin, and 5-hydroxyindoleacetic acid in a single mouse brain. Anal Biochem. 1969 Aug;30(2):161–179. doi: 10.1016/0003-2697(69)90387-x. [DOI] [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