Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1986 May;88(1):285–290. doi: 10.1111/j.1476-5381.1986.tb09497.x

Stereoselective accumulation of hydroxylated metabolites of amphetamine in rat striatum and hypothalamus.

D F Dougan, A M Duffield, P H Duffield, D N Wade
PMCID: PMC1917092  PMID: 3708221

Abstract

The stereoselective accumulation of alpha-methyl-p-tyramine (AMPT) and alpha-methyl-p-octopamine (AMPO) in rat striatum and hypothalamus after acute and chronic administration of the (+)- and (-)-isomers of amphetamine (Amphet) and the acute administration of (+)- and (-)-AMPT has been investigated by chemical ionization gas chromatography mass spectrometry (c.i.g.c.m.s.). Two h after the administration of (+)- or (-)-AMPT (5 mg kg-1 i.p.), the concentrations of the isomers in striatal tissue were approximately equal; 18 h later, the concentration of the (+)-isomer was 10 times that of the (-)-isomer. The concentrations of AMPO in the striatum and hypothalamus 20 h after administration of (+)-AMPT were 68 ng g-1 and 484 ng g-1 respectively. After the administration of the (-)-isomer of AMPT, small quantities of AMPO were detected in both brain areas. Twenty h after the last of 7 daily injections of (+)-Amphet (5 mg kg-1, i.p.), the concentration of AMPO in the hypothalamus was 5.4 times the concentration at 20 h after one injection. In the striatum, the corresponding ratio for AMPO was 3.5 and for AMPT was 2.5. These data indicate that, although both isomers of AMPT formed from Amphet administered systemically, cross the blood brain barrier, the (+)-isomers AMPT and AMPO are preferentially stored in striatal and hypothalamic aminergic nerve terminals. The accumulations of AMPT and AMPO in rat striatum and hypothalamus after chronic administration of Amphet demonstrates that these metabolites persist in neuronal storage in these brain areas for days after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
285

Selected References

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

  1. AXELROD J. Studies on sympathomimetic amines. II. The biotransformation and physiological disposition of d-amphetamine, d-p-hydroxyamphetamine and d-methamphetamine. J Pharmacol Exp Ther. 1954 Mar;110(3):315–326. [PubMed] [Google Scholar]
  2. Browne R. G., Segal D. S. Metabolic and experimental factors in the behavioral response to repeated amphetamine. Pharmacol Biochem Behav. 1977 May;6(5):545–552. doi: 10.1016/0091-3057(77)90115-0. [DOI] [PubMed] [Google Scholar]
  3. Cattabeni F., Racagni G., Groppetti A. Use of mass fragmentography to detect subcellular localization of drug metabolites acting as false transmitters. Adv Biochem Psychopharmacol. 1973;7:45–55. [PubMed] [Google Scholar]
  4. Cho A. K., Schaffer J. C., Fischer J. F. Accumulation of 4-hydroxyamphetamine by rat striatal homogenates. Biochem Pharmacol. 1975 Aug 15;24(16):1540–1542. doi: 10.1016/0006-2952(75)90034-9. [DOI] [PubMed] [Google Scholar]
  5. Danielson T. J., Boulton A. A. Distribution and occurrence of amphetamine and p-hydroxyamphetamine in tissues of the rat after injection of d-amphetamine sulfate. Eur J Pharmacol. 1976 Jun;37(2):257–264. doi: 10.1016/0014-2999(76)90033-9. [DOI] [PubMed] [Google Scholar]
  6. Duffield P. H., Dougan D. F., Wade D. N., Duffield A. M. A chemical ionization gas chromatographic mass spectrometric assay for octopamine and tyramine in rat brain. Biomed Mass Spectrom. 1981 Apr;8(4):170–173. doi: 10.1002/bms.1200080408. [DOI] [PubMed] [Google Scholar]
  7. Goldstein M., Anagnoste B. The conversion in vivo of D-amphetamine to (+)-p-hydroxynorephedrine. Biochim Biophys Acta. 1965 Aug 24;107(1):166–168. doi: 10.1016/0304-4165(65)90412-5. [DOI] [PubMed] [Google Scholar]
  8. Gordis E. Gas-chromatographic resolution of optical isomers in microgram samples of amphetamine. Biochem Pharmacol. 1966 Dec;15(12):2124–2126. doi: 10.1016/0006-2952(66)90245-0. [DOI] [PubMed] [Google Scholar]
  9. Groppetti A., Costa E. Tissue concentrations of p-hydroxynorephedrine in rats injected with d-amphetamine: effect of pretreatment with desipramine. Life Sci. 1969 Jun 1;8(11):653–665. doi: 10.1016/0024-3205(69)90027-7. [DOI] [PubMed] [Google Scholar]
  10. Jori A., Caccia S., Guiso A., Ballabio M., Garattini S. Selective storage of p-hydroxy-d-amphetamine in the dopaminergic nerve terminals. Biochem Pharmacol. 1979 Apr 1;28(7):1205–1207. doi: 10.1016/0006-2952(79)90329-0. [DOI] [PubMed] [Google Scholar]
  11. Kuhn C. M., Schanberg S. M., Breese G. R. Metabolism of amphetamine by rat brain tissue. Biochem Pharmacol. 1978 Feb 1;27(3):343–351. doi: 10.1016/0006-2952(78)90238-1. [DOI] [PubMed] [Google Scholar]
  12. Lewander T. Displacement of brain and heart noradrenaline by p-hydroxynorephedrine after administration of p-hydroxyamphetamine. Acta Pharmacol Toxicol (Copenh) 1971;29(1):20–32. doi: 10.1111/j.1600-0773.1971.tb00579.x. [DOI] [PubMed] [Google Scholar]
  13. SJOERDSMA A., von STUDNITZ W. Dopamine-beta-oxidase activity in man, using hydroxyamphetamine as substrate. Br J Pharmacol Chemother. 1963 Apr;20:278–284. doi: 10.1111/j.1476-5381.1963.tb01467.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Segal D. S., Mandell A. J. Long-term administration of d-amphetamine: progressive augmentation of motor activity and stereotypy. Pharmacol Biochem Behav. 1974 Mar-Apr;2(2):249–255. doi: 10.1016/0091-3057(74)90060-4. [DOI] [PubMed] [Google Scholar]
  15. Taylor W. A., Sulser F. Effects of amphetamine and its hydroxylated metabolites on central noradrenergic mechanisms. J Pharmacol Exp Ther. 1973 Jun;185(3):620–632. [PubMed] [Google Scholar]

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

RESOURCES