Summary
The concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured in the striatum of rats after i.p. injection of dipropyl-2-aminotetralin and the four positional isomers of monohydroxy-dipropyl-2-aminotetralin. All compounds except 8-OH dipropylaminotetralin caused a decrease in DOPAC-and HVA-concentrations. In addition, 5-OH-dipropylaminotetralin produced a small elevation in DA concentrations. In contrast, 7-OH dipropylaminotetralin, in doses of 100 μmol/kg and more, decreased DA to 50% and initially increased HVA and DOPAC to about 200%, after which the concentrations of the metabolites fell to 30% or less. The 5-OH isomer was found to be the most potent compound, decreasing HVA concentrations to 70% at a dose of 0.14 μmol/kg. The potencies are compared to those of catechol-group containing DA-agonists such as apomorphine and N,N-dipropyl-5,6-dihydroxy-2-aminotetralin. In addition, a comparison is made with reported behavioural data. It is suggested that the more active N-alkylated 2-aminotetralins have a conformation which corresponds to that of the α rotamer of dopamine.
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Cannon, J. G.: Chemistry of dopaminergic agonists. In: Advances in neurology, Vol. 9 (D. B. Calne, T. N. Chase and A. Barbeau, eds.), pp. 177–183. New York: Raven Press 1975
Cannon, J. G., Lee, T., Goldman, H. D., Costall, B., Naylor, R. J.: Cerebral dopamine agonist properties of some 2-aminotetralin derivatives after peripheral and intracerebral administration. J. Med. Chem. 20, 1111–1116 (1977)
Cannon, J. G., Costall, B., Laduron, P. M., Leysen, J. E., Naylor, R. J.: Effects of some derivatives of 2-aminotetralin on dopaminesensitive adenylate cyclase and on the binding of (3H) haloperidol to neuroleptic receptors in the rat striatum. Biochem. Pharmacol 27, 1417–1420 (1978a)
Cannon, J. G., Hsu, F. L., Long, J. P., Flynn, J. R., Costall, B., Naylor, R. J.: Preparation and biological actions of some symmetrically N,N-disubstituted dopamines. J. Med. Chem. 21, 248–253 (1978b)
Feenstra, M. G. P., Rollema, H., Horn, A. S., Dijkstra, D., Grol, C. J., Westerink, B. H. C., Westerbrink, A.: Effect of dihydroxy-2-aminotetralin derivatives on dopamine metabolism in the rat striatum. Naunyn-Schmiedeberg's Arch. Pharmacol. 310, 219–225 (1980)
Fuxe, K., Fredholm, B. B., Ogren, S. O., Agnati, L. F., Hökfelt, T., Gustafsson, J. A.: Ergot drugs and central monoaminergic mechanisms: a histochemical, biochemical and behavioral analysis. Fed. Proc. 37, 2181–2191 (1978)
Geissler, H. E.: 3-(2-Dipropylamino-äthyl)-phenol, ein neuer, selektiver dopaminerger Agonist. Arch. Pharm. 310, 749–756 (1977)
Grol, C. J.: The chemistry of dopamine. In: The neurobiology of dopamine, (A. S. Horn, J. Korf and B. H. C. Westerink, eds), pp. 7–27. London: Academic Press 1979
Grol, C. J., Rollema, H.: Conformational analysis of dopamine by the INDO molecular orbital method. J. Pharm. Pharmacol. 29, 153–156 (1977)
Grol, C. J., Rollema, H., Asselbergs, H. W.: The effect of 2-substitution on conformations and brain concentrations of phenothiazine-neuroleptics in relation to dopamine-antagonism. J. Pharm. Pharmacol. 31, 667–671 (1979)
Hacksell, U., Svensson, U., Nilsson, J. L. G., Hjorth, S., Carlsson, A., Wikström, H., Lindberg, P., Sanchez, D.: N-alkylated 2-aminotetralins: Central dopamine-receptor stimulating activity. J. Med. Chem. 22, 1469–1475 (1979)
Lark, P. D., Craven, B. R., Bosworth, R. C. L.: The handling of chemical data. Oxford: Pergamon Press 1968
McDermed, J. D., McKenzie, G. M., Phillips, A. P.: Synthesis and pharmacology of some 2-aminotetralins. J. Med. Chem. 18, 362–367 (1975)
McDermed, J. D., McKenzie, G. M., Freeman, H. S.: Synthesis and dopaminergic activity of (±)-, (+)- and (−)-2-dipropylamino-5-hydroxy-1,2,3,4-tetrahydronaphthalene. J. Med. Chem. 19, 547–549 (1976)
McDermed, J. D., Freeman, H. S., Ferris, R. M.: Enantioselectivity in the binding of (+)- and (−)-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene and related agonists to dopamine receptors. In: Catecholamines: Basic and clinical frontiers, Vol. I (E. Usdin, I. Kopin and J. Barchas, eds.), pp. 568–570. New York: Pergamon Press 1979
Neumeyer, J. L., Granchelli, F. E., Fuxe, K., Ungerstedt, U, Corrodi, H.: Aporphines. 11. Synthesis and dopaminergic activity of monohydroxyaporphines. Total synthesis of (±)-11-hydroxyaporhine, (±)-11-hydroxynoraporphine, and (±)-11-hydroxy-N-n-propylnoraporphine. J. Med. Chem. 17, 1090–1095 (1974)
Rollema, H., Westerink, B. H. C., Grol, C. J.: Correlation between neuroleptic-induced suppression of stereotyped behaviour and HVA concentrations in rat brain. J. Pharm. Pharmacol. 28, 321–323 (1976)
Rollema, H., Westerink, B. H. C., Mulder, T. B. A., Dijkstra, D., Feenstra, M. G. P., Horn, A. S.: The significance of COMT-activity in controlling dopamine-agonist levels in brain and serum: Studies with a prodrug and a metabolite of 6,7-ADTN. Eur. J. Pharmacol. 64, 313–323 (1980)
Rusterholz, D. B., Long, J. P., Flynn, J. R., Cannon, J. G., Lee, T., Pease, J. P., Clemens, J. A., Wong, D. T., Bymaster, F. P.: Dopaminergic effects of non-hydroxylated rigid analogs of apomorphine. Eur. J. Pharmacol 52, 73–82 (1979)
Schoenfeld, R. I., Neumeyer, J. L., Dafeldecker, W., Roffler-Tarlov, S.: Comparison of structural and stereoisomers of apomorphine on stereotyped sniffing behavior of the rat. Eur. J. Pharmacol. 30, 63–68 (1975)
Schorderet, M., McDermed, J. D., Magistretti, P.: Dopamine receptors and cyclic AMP in rabbit retina: a pharmacological and stereochemical analysis using semi-rigid analogs of dopamine (aminotetralins) and thioxanthene isomers. J. Physiol. (Paris) 74, 509–513 (1978)
Seeman, P., Titeler, M., Tedesco, J., Weinreich, P., Sinclair, D.: Brain receptors for dopamine and neuroleptics. In: Advances in biochemical psychopharmacology, Vol. 19 (P. J. Roberts, G. N. Woodruff and L. L. Iversen, ed), pp. 167–176. New York: Raven Press 1978
Tedesco, J. L., Seeman, P., McDermed, J. D.: The conformation of dopamine at its receptor: Monohydroxy-2-aminotetralin enantiomers and positional isomers. Mol. Pharmacol. 16, 369–381 (1979)
Uretsky, N. J., Snodgrass, S. R., Lorenzo, A. V.: Studies on the mechanism of depletion of striatal dopamine by α-methyl-mtyrosine. J. Pharmacol. Exp. Ther. 195, 465–479 (1975)
Westerink, B. H. C.: The effects of drugs on dopamine biosynthesis and metabolism in the brain. In: The neurobiology of dopamine (A. S. Horn, J. Korf and B. H. C. Westerink, eds), pp. 255–291. London: Academic Press 1979
Westerink, B. H. C., Korf, J.: Rapid concurrent automated fluorimetric assay of noradrenaline, dopamine, 3,4-dihydroxyphenylacetic, acid, homovanillic acid and 3-methoxytyramine in milligram amounts of nervous tissue after isolation on Sephadex G 10. J. Neurochem. 29, 697–706 (1977)
Westerink, B. H. C., Dijkstra, D., Feenstra, M. G. P., Grol, C. J., Horn, A. S., 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. 61, 7–15 (1980)
Wikström, H., Lindberg, P., Martinson, P., Hjorth, S., Carlsson, A., Hacksell, U., Svensson, U., Nilsson, J. L. G.: Pivaloyl esters of N,N-dialkylated dopamine congeners. Central dopaminereceptor stimulating activity. J. Med. Chem. 21, 864–867 (1978)
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Feenstra, M.G.P., Rollema, H., Dijkstra, D. et al. Effect of non-catecholic 2-aminotetralin derivatives on dopamine metabolism in the rat striatum. Naunyn-Schmiedeberg's Arch. Pharmacol. 313, 213–219 (1980). https://doi.org/10.1007/BF00505736
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DOI: https://doi.org/10.1007/BF00505736