Abstract
In vivo clorgyline (5 mg/kg) and (-)-deprenyl (5 mg/kg) selectively inhibit monoamine oxidase (MAO) type A and B activities in rat brain hypothalamus and caudate nucleus using 5-hydroxytryptamine (5-HT), noradrenaline (NA), and beta-phenylethylamine (PEA) as substrates. Clorgyline induces a significant increase in NA concentrations of hypothalamus and caudate nucleus; however (-)-deprenyl is without effect. The combination of clorgyline and (-)-deprenyl at the above doses completely inhibits both forms of MAO, resulting in an even greater increase in NA levels in both brain areas than observed with clorgyline. The non-selective inhibitor tranylcypromine (5 mg/kg) produced a similar effect. Rats pretreated with the selective or the non-selective inhibitors but given L-DOPA (50 mg/kg) have a similar pattern of brain NA, but its concentrations are higher in both brain regions. The results indicate that although in vitro NA may be an exclusive substrate for MAO type A, in vivo, when this enzyme form is selectively inhibited, NA at high concentrations can be a substrate for MAO type B.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- CHANG C. C. A SENSITIVE METHOD FOR SPECTROPHOTOFLUOROMETRIC ASSAY OF CATECHOLAMINES. Int J Neuropharmacol. 1964 Dec;3:643–649. doi: 10.1016/0028-3908(64)90089-9. [DOI] [PubMed] [Google Scholar]
- Ekstedt B. Substrate specificity of the different forms of monoamine oxidase in rat liver mitochondria. Biochem Pharmacol. 1976 May 15;25(10):1133–1138. doi: 10.1016/0006-2952(76)90359-2. [DOI] [PubMed] [Google Scholar]
- Fowler C. J., Tipton K. F. Deamination of 5-hydroxytryptamine by both forms of monoamine oxidase in the rat brain. J Neurochem. 1982 Mar;38(3):733–736. doi: 10.1111/j.1471-4159.1982.tb08692.x. [DOI] [PubMed] [Google Scholar]
- Goridis C., Neff N. H. Evidence for a specific monoamine oxidase associated with sympathetic nerves. Neuropharmacology. 1971 Sep;10(5):557–564. doi: 10.1016/0028-3908(71)90021-9. [DOI] [PubMed] [Google Scholar]
- Green A. R., Mitchell B. D., Tordoff A. F., Youdim M. B. Evidence for dopamine deamination by both type A and type B monoamine oxidase in rat brain in vivo and for the degree of inhibition of enzyme necessary for increased functional activity of dopamine and 5-hydroxytryptamine. Br J Pharmacol. 1977 Jul;60(3):343–349. doi: 10.1111/j.1476-5381.1977.tb07506.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Green A. R., Youdim M. B. Effects of monoamine oxidase inhibition by clorgyline, deprenil or tranylcypromine on 5-hydroxytryptamine concentrations in rat brain and hyperactivity following subsequent tryptophan administration. Br J Pharmacol. 1975 Nov;55(3):415–422. doi: 10.1111/j.1476-5381.1975.tb06946.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnston J. P. Some observations upon a new inhibitor of monoamine oxidase in brain tissue. Biochem Pharmacol. 1968 Jul;17(7):1285–1297. doi: 10.1016/0006-2952(68)90066-x. [DOI] [PubMed] [Google Scholar]
- Yang H. Y., Neff N. H. The monoamine oxidases of brain: selective inhibition with drugs and the consequences for the metabolism of the biogenic amines. J Pharmacol Exp Ther. 1974 Jun;189(3):733–740. [PubMed] [Google Scholar]