Summary
Several dopamine (DA) receptor agonists, notably N,N-dipropyl-2-aminotetralin analogues differing in the number and position of phenolic hydroxyl groups, were evaluated in model systems for pre- and postsynaptic dopaminergic activity. Apomorphine, piribedil and pergolide were included for comparison. All compounds inhibited the γ-butyrolactone (GBL)-induced increase in DA concentrations in the rat striatum and olfactory tubercle, although a dosedependency could not be demonstrated for one of the compounds, i.e. N,N-dipropyl-2-amino-5,6-dihydroxytetralin. In addition to the reversal of the DA-increase all compounds decreased the HVA and DOPAC levels in a dose-dependent manner, in much the same way as in normal, non GBL-pretreated rats.
The potencies of the drugs to decrease HVA in normal rats and to inhibit the DA-increase and to decrease HVA in GBL-pretreated rats, both in the striatum and the olfactory tubercle were compared with each other and with the potencies to induce stereotyped behaviour. It may be concluded that (1) N,N-dipropyl-2-amino-7-hydroxytetralin shows the largest difference in activity in the biochemical and the behavioural models, suggesting a selective presynaptic activity. This was corroborated by the appearance of a marked hypomotility after low doses of this compound; (2) The potencies to decrease striatal HVA concentrations are generally somewhat different from the potencies to inhibit GBL-induced DA-increases, but appear to be comparable to the potencies to inhibit GBL-induced dihydroxyphenylalanine (DOPA)-increases; (3) There is no indication that the DA agonists in general are more potent at presynaptic receptors in the tubercle than in the striatum.
Similar content being viewed by others
References
Anden NE, Rubenson A, Fuxe K, Hökfelt T (1967) Evidence for dopamine receptor stimulation by apomorphine. J Pharm Pharmacol 19:627–629
Anden NE, Strömbom U, Svensson TH (1973) Dopamine and noradrenaline receptor stimulation: Reversal of reserpine-induced suppression of motor activity. Psychopharmacologia 29:289–298
Bannon MJ, Bunney EB, Zigun JR, Skirboll LR, Roth RH (1980) Presynaptic dopamine receptors: Insensitivity to kainic acid and the development of supersensitivity following chronic haloperidol. Naunyn-Schmiedeberg's Arch Pharmacol 312:161–165
Cannon JG, Lee T, Goldman HD, Costall B, Naylor RJ (1977) Cerebral dopamine agonist properties of some 2-aminotetralin derivatives after peripheral and intracerebral administration. J Med Chem 20:1111–1116
Carlsson A (1975) Receptor-mediated control of dopamine metabolism. In: Usdin E, Bunney WE (eds) Pre- and postsynaptic receptors. Marcel Dekker, New York, pp 49–63
Costall B, Naylor RJ, Cannon JG, Lee T (1977) Differentiation of dopamine mechanisms mediating stereotyped behaviour and hyperactivity in the nucleus accumbens and the caudate-putamen. J Pharm Pharmacol 29:337–342
Costall B, Naylor RJ (1981) The hypotheses of different dopamine receptor mechanisms. Life Sci 28:215–229
Di Chiara G, Porceddu ML, Fratta W, Gessa GL (1977) Postsynaptic receptors are not essential for dopaminergic feedback regulation. Nature 267:270–272
DiGiulio AM, Groppetti A, Cattabeni F, Galli CL, Maggi A, Algeri S, Ponzio F (1978) Significance of dopamine metabolites in the evaluation of drugs acting on dopaminergic neurons. Eur J Pharmacol 52:201–207
Feenstra MGP, Rollema H, Horn AS, Dijkstra D, Grol CJ, Westerink BHC, Westerbrink A (1980a) Effect of dihydroxy-2-amino-tetralin derivatives on dopamine metabolism in the rat striatum. Naunyn-Schmiedeberg's Arch Pharmacol 310:219–225
Feenstra MGP, Rollema H, Dijkstra D, Grol CJ, Horn AS, Westerink BHC (1980) Effect of non-catecholic 2-aminotetralin derivatives on dopamine metabolism in the rat striatum. Naunyn-Schmiedeberg's Arch Pharmacol 313:213–219
Goodale DB, Rusterholz DB, Long JP, Flynn JR, Walsh B, Cannon JG, Lee T (1980) Neurochemical and behavioural evidence for a selective presynaptic dopamine receptor agonist. Science 210:1141–1143
Hjorth S, Carlsson A, Wikström H, Lindberg P, Sanchez D, Hacksell U, Arvidsson LE, Svensson U, Nilsson JLG (1981) 3-PPP, a new centrally acting DA-receptor agonist with selectivity for autoreceptors. Life Sci 28:1225–1238
Horn AS, Feenstra MGP, Grol CJ, Rollema H, van Oene JC, Westerink BHC (1981) Multiple dopamine receptors: fact, fiction or confusion? Pharm Weekblad Sci Ed, 3:145–165
Horn AS, de Vries J, Dijkstra D, Mulder AH (1982) Is TL-99 a selective presynaptic dopamine receptor agonist? Eur J Pharmacol 83:35–45
Kebabian JW, Calne DB (1979) Multiple receptors for dopamine. Nature 277:93–96
Kehr W, Carlsson A, Lindquist M, Magnusson T, Atack C (1972) Evidence for a receptor-mediated feedback control of striatal tyrosine hydroxylase activity. J Pharm Pharmacol 24:744–747
Langer SZ, Arbilla S, Kamal L, Cantrill R (1983) Peripheral and central dopamine receptors modulating the release of neurotransmitters. Acta Pharmaceut Suec Suppl 1:108–117
Lark PD, Craven BR, Bosworth RCL (1968) The handling of chemical data. Pergamon Press, Oxford
Lehmann J, Briley M, Langer SZ (1983) Characterization of dopamine autoreceptor and 3H spiperone binding sites in vitro with classical and novel dopamine receptor agonists. Eur J Pharmacol 88:11–26
McDermed JD, McKenzie GM, Phillips AP (1975) Synthesis and pharmacology of some 2-aminotetralins. Dopamine receptor agonists. J Med Chem 18:362–367
McDermed JD, McKenzie GM, Freeman HS (1976) Synthesis and dopaminergic activity of (±), (+) and (−)-2-dipropylamino-5-hydroxy-1,2,3,4-tetrahydronaphthalene. J Med Chem 19:547–549
McDermed JD, Freeman HS, Ferris RM (1979) Enantioselectivity in the binding of (+)- and (−)-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene and related agonists to dopamine receptors. In: Usdin E, Kopin J, Barchas J (eds) Catecholamines: Basic and clinical frontiers, vol 1. Pergamon Press, New York, pp 568–570
Meltzer H (1980) Relevance of dopamine autoreceptors for psychiatry: Preclinical and clinical studies. Schizophrenia Bull 6:456–475
Nowycky MC, Roth RH (1979) Presynaptic dopamine receptors. Development of supersensitivity following treatment with fluphanazine decanoate. Naunyn-Schmiedeberg's Arch Pharmacol 300:247–254
Pastor G, Fallon S, Welch JJ, Liebeman JM (1983) Postsynaptic dopamine agonist properties of TL-99 are revealed by yohimbine cotreatment. Eur J Pharmacol 87:459–464
Rabey JM, Passeltiner P, Merkey K, Asano T, Goldstein M (1981) Stimulation of pre- and postsynaptic dopamine receptors by an ergoline and by a partial ergoline. Brain Res 225:347–356
Roos BE (1969) Decrease in homovanillic acid as evidence for dopamine receptor stimulation by apomorphine in the neostriatum of the rat. J Pharm Pharmacol 21:263–264
Roth RH, Murrin C, Walters JR (1976) Central dopaminergic neurons: Effects of alterations in impulse flow on the accumulation of dihydroxyphenylacetic acid. Eur J Pharmacol 36:163–171
Seeman P (1980) Brain dopamine receptors. Pharmacol Rev 32:229–313
Seiler MP, Markstein R (1982) Further characterization of structural requirements for agonists at the striatal dopamine D1-receptor. Mol Pharmacol 22:281–289
Sethy VH, van Woert MH (1974) Regulation of striatal acetylcholine concentration by dopamine receptors. Nature 251:529–530
Skirboll LR, Grace AA, Bunney BS (1979) Dopamine-auto- and postsynaptic receptors: Electrophysiological evidence for differential sensitivity to dopamine agonists. Science 206:80–82
Starke K, Reimann W, Zumstein A, Hertting G (1978) Effect of dopamine receptor agonists and antagonists on release of dopamine in the rabbit caudate nucleus in vitro. Naunyn-Schmiedeberg's Arch Pharmacol 305:27–36
Strömbom U (1976) Catecholamine receptor agonists. Effects on motor activity and rate of tyrosine hydroxylation in mouse brain. Naunyn-Schmiedeberg's Arch Pharmacol 292:167–176
Tissari HA, Porceddu ML, Argiolas A, Di Chiara G, Gessa GL (1978) Dopamine-synthesis and tyrosine hydroxylase are regulated by independent DA-receptor mediated mechanisms. Life Sci 23:653–658
Ungerstedt U (1979) Central dopamine mechanisms and unconditioned behaviour. In: Horn AS, Korf J, Westerink BHC (eds) The neurobiology of dopamine. Academic Press, London, pp 577–596
Waggoner WG, McDermed JD, Leighton HJ (1980) Presynaptic regulation of tyrosine hydroxylase activity in rat striatal synaptosomes by dopamine analogs. Mol Pharmacol 18:91–99
Walters JR, Roth RH (1974) Dopaminergic neurons: Drug-induced antagonism of the increase in tyrosine hydroxylase activity produced by cessation of impulse flow. J Pharmacol Exp Ther 191:82–91
Westerink BHC (1977) The effect of midbrain lesions on the regulation of metabolism in the substantia nigra and the striatum of rat brain. In: Regional dopamine metabolism in rat brain. Ph. D. Thesis, University of Groningen, pp 91–105
Westerink BHC, Korf J (1977) Rapid concurrent automated fluorimetric assay of noradrenaline, dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid 3-methoxytyramine in milligram amounts of nervous tissue after isolation on Sephadex G-10. J Neurochem 29:697–706
Westerink BHC, Mulder TBA (1981) Determination of picomole amounts of dopamine, noradrenaline, 3,4-dihydroxyphenylalanine, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid in nervous tissue after one-step purification on Sephadex G-10, using high-performance liquid chromatography with a novel type of electrochemical detection. J Neurochem 36:1449–1462
Westerink BHC, Spaan SJ (1982) Estimation of the turnover of 3-methoxytyramine in the rat striatum by HPLC with electrochemical detection: Implication for the sequence in the cerebral metabolism of dopamine. J Neurochem 38:342–347
Westfall TC, Besson MJ, Giorguieff MF, Glowinski J (1976) The role of presynaptic receptors in the release and synthesis of 3H-dopamine by slices of rat striatum. Naunyn-Schmiedeberg's Arch Pharmacol 292:279–287
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Feenstra, M.G.P., Sumners, C., Goedemoed, J.H. et al. A comparison of the potencies of various dopamine receptor agonists in models for pre- and postsynaptic receptor activity. Naunyn-Schmiedeberg's Arch. Pharmacol. 324, 108–115 (1983). https://doi.org/10.1007/BF00497015
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00497015