Abstract
Thein vitro inhibition of rat brain monoamine oxidase type A (Mao-a) by various dopamine analogues is reported and compared to some established inhibitors of the enzyme. The estimated ic50's were found to be in the range 10−5–10−3 mol/1. This makes these compounds more than 10 000 times less potent than the selectiveMao-a inhibitor harmaline and more than 10 times less potent than the selectiveMao-b inhibitors pargyline and deprenyl. When the brain concentrations that are reached after peripheral administration of these drugs are taken into account it is unlikely that inhibition ofMao is relevant to their effects as has been suggested. Also the endogenous brain concentrations of some tetrahydroisoquinolines are probably too low to produce an inhibition of the enzyme.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
di Chiara G, Balakleevsky A, Porceddu ML, Tagliamonte A, Gessa GL. Inhibition by apomorphine of dopamine deamination in the rat brain. J Neurochem 1974;23:1105–8.
Hoffmann IS, Naylor RJ, Cubeddu LX. Presynaptic effects of 2-aminotetralins on striatal dopaminergic neurons. J Pharmacol Exp Ther 1980;215:486–93.
Costall B, Lim SK, Naylor RJ, Cannon JG. On the preferred rotameric conformation for dopamine agonist action: an illusory quest? J Pharm Pharmacol 1982;34:246–54.
Yamanaka Y. Effect of salsolinol on rat brain and liver monoamine oxidase. Jpn J Pharmacol 1971;21:833–6.
Sjöquist B, Magnuson E. Analysis of salsolinol and salsoline in biological samples using deuterium-labelled internal standards and gas chromatography-mass spectrometry. J Chromatogr 1980;183:17–24.
Barker SA, Monti JA, Tolbert LC, Brown GB, Christian ST. Gas chromatographic-mass spectrometric evidence for the identification of 6,7-dihy-droxy-1,2,3,4-tetrahydroisoquinoline as a normal constituent of rat brain. Biochem Pharmacol 1981;30:2461–8.
Waldmeier PC, Delini-Stula A, Maître L. Preferential deamination of dopamine by an A type monoamine oxidase in rat brain. Naunyn Schmiedebergs Arch Pharmacol 1976;292:9–14.
Demarest KT, Moore KE. Type A monoamine oxidase catalyzes the intraneuronal deamination of dopamine within nigrostriatal, mesolimbic, tuberoinfundibular and tuberohypophyseal neurons in the rat. J Neural Transm 1981;52:175–87.
Feenstra MGP, Rollema H, Horn AS, Dijkstra D, Grol CJ, Westerink BHC, Westerbrink A. Effect of dihydroxy-2-aminotetralin derivatives on dopamine metabolism in the rat striatum. Naunyn Schmiedebergs Arch Pharmacol 1980;310:219–25.
Westerink BHC, Dijkstra D, Feenstra MGP, Grol CJ, Horn AS, Rollema H, Wirix E. Dopaminergic prodrugs: Brain concentrations and neurochemical effects of 5,6- and 6,7-Adtn after administration as dibenzoyl esters. Eur J Pharmacol 1980;61:7–15.
Feenstra MGP, Rollema H, Mulder TBA, Westerink BHC, Horn AS. Amperometric detection of low concentrations of dopamine receptor agonists after liquid Chromatographic sample enrichment: Effect of O-methylation on brain concentrations of dipropyl-5,6-Adtn and dipropyl-6,7-Adtn. Life Sci 1983;32:459–65.
Robinson DS, Lovenberg W, Keiser H, Sjoerdsma A. Effects of drugs on human blood platelet and plasma amine oxidase activity in vitro and in vivo. Biochem Pharmacol 1968;17:109–19.
Owen F, Bourne RC, Lai JCK, Williams R. The heterogeneity of monoamine oxidase in distinct populations of rat brain mitochondria. Biochem Pharmacol 1977;26:289–92.
Schoepp DD, Azzaro AJ. Specificity of endogenous substrates for types A and B monoamine oxidase in rat striatum. J Neurochem 1981;36:2025–31.
Westerink BHC, Horn AS. Do neuroleptics prevent the penetration of dopamine agonists into the brain? Eur J Pharmacol 1979;58:39–48.
Demarest KT, Smith DJ, Azzaro AJ. The presence of the type A form of monoamine oxidase within nigrostriatal dopamine-containing neurons. J Pharmacol Exp Ther 1980;215:461–8.
Roberts PJ, Davis A.Adtn (2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene): A prototype for possible dopaminergic false transmitters? In: Roberts PJ, Woodruff GN, Iversen LL, red. Dopamine, Advances in Biochemical Psychopharmacology Vol. 19. New York: Raven Press, 1978:177–91.
Westerink BHC, Dijkstra D, Feenstra MGP, Horn AS, Rollema H. Selective storage in vivo of 5,6-Adtn in dopamine-rich areas of the rat brain. Eur J Pharmacol 1980;64:115–21.
Heikkila R, Cohen G, Diembiec D. Tetrahydroisoquinoline alkaloids: Uptake by rat brain homogenates and inhibition of catecholamine uptake. J Pharmacol Exp Ther 1971;179:250–8.
Cohen G, Mytilineou C, Barrett RE. 6,7-Dihydroxy-tetrahydroisoquinoline: Uptake and storage by peripheral sympathetic nerve of the rat. Science 1972;175:1269–72.
Melchior C, Collins MA. The route and significance of endogenous synthesis of alkaloids in animals.Crc Crit Rev Toxicol 1982;313–56.
Collins AC, Cashaw JL, Davis VE. Dopamine-derived tetrahydroisoquinoline alkaloids-inhibitors of neuroamine metabolism. Biochem Pharmacol 1973;22:2337–48.
Meller E, Friedman J, Schweizer JW, Friedhoff AJ. Tetrahydro-β-carbolines: specific inhibitors of type A monoamine oxidase in rat brain. J Neurochem 1977;28:995–1000.
Glover V, Liebowitz J, Armando I, Sandler M. β-Carbolines as selective monoamine oxidase inhibitors: in vivo implications. J Neural Transm 1982;54:209–18.
Author information
Authors and Affiliations
Additional information
In honour of Professor Faber on the occasion of his 25-years' professorate.
Rights and permissions
About this article
Cite this article
Feenstra, M.G.P., van der Velden, T., Dijkstra, D. et al. Inhibition of rat brain monoamine oxidase type A by 2- aminotetralin and tetrahydroisoquinoline analogues of dopamine. Pharmaceutisch Weekblad Scientific Edition 5, 131–133 (1983). https://doi.org/10.1007/BF01961468
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01961468