Skip to main content
SpringerLink
Log in

Effect of monoamine oxidase A and B and of catechol-O-methyltransferase inhibition on L-DOPA-induced circling behavior

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Summary

The effect of enzyme-inhibiting adjuvants on L-DOPA + benserazide-induced contralateral turning in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats was studied. Both the number of turns and the duration of turning were examined. Inhibition of MAO-A with 10mg/kg Ro 41–1049 increased both parameters; inhibition of COMT with 10mg/kg Ro 40–7592 had a similar effect. In contrast, inhibition of MAO-B with 10mg/kg Ro 19–6327 did not change turning behavior. A further potentiation of turning behavior was observed after the combined administration of both the MAO-A and COMT inhibitor. MAO-A inhibition in conjunction with MAO-B inhibition prolonged the duration of L-DOPA-induced turning but had no effect on the number of turns. However, in conjunction with COMT inhibition, 10mg/kg of the MAO-B inhibitor, Ro 19–6327, significantly affected both the number and duration of turning behavior. An even further potentiation of turning behavior was observed after the combined administration of all three enzyme-inhibitors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Acquas E, Carboni E, de Ree RHA, Da Prada M, Di Chiara G (1992) Extracellular concentrations of dopamine and metabolites in the rat caudate after oral administration of a novel catechol-O-methyltransferase inhibitor Ro 40-7592. J Neurochem 59(1): 326–330

    Google Scholar 

  • Barbeau A (1981) The use of L-DOPA in Parkinson's disease: a 20 year follow-up. Trends Pharmacol Sci 2: 297–299

    Google Scholar 

  • Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F (1973) Brain dopamine and the syndromes of Parkinson and Huntington: clinical, morphological, and neurochemical correlation's. J Neurol Sci 21: 297–301

    Google Scholar 

  • Birkmayer W, Riederer P, Youdim MBH, Linnauer W (1975) The potentiation of the akinetic effect after L-DOPA treatment by an inhibitor a MAO-B, deprenyl. J Neural Transm 36: 303–326

    Google Scholar 

  • Borgulya J, Bruderer H, Bernauer K, Zürcher G, Da Prada M (1989) Catechol-O-methyltransferease-inhibiting pyrocatechol deratives: synthesis and structure-activity studies. Helv Chim Acta 72: 952–968

    Google Scholar 

  • Brannan T, Martinez-Tica J, Yahr MD (1992) Catechol-O-methyltransferase inhibition increases striatal L-DOPA and dopamine: an in vivo study in rats. Neurology 42: 683–685

    Google Scholar 

  • Butcher SP, Fairbrother IS, Kelly JS, Arbuthnott GW (1990) Effect of selective monoamine oxidase inhibitors on the in vivo release and metabolism of dopamine in the rat striatum. J Neurochem 55: 981–988

    Google Scholar 

  • Buu NT (1989) Modification of vesicular dopamine and norepinephrine by monoamine oxidase inhibiters. Biochem Pharmacol 38: 1692–1695

    Google Scholar 

  • Buu NT, Angers M (1987) Effect of different monoamine oxidase inhibitors on the metabolism of L-DOPA in the rat brain. Biochem Pharmacol 36: 1731–1735

    Google Scholar 

  • Christmas AJ, Coulson CJ, Maxwell DP, Riddel D (1972) A comparison of the pharmacological and biochemical properties of substrate selective monoamine oxidase inhibitors. Br J Pharmacol 45: 490–503

    Google Scholar 

  • Colzi A, D'Agostini F, Kettler R, Borroni E, DaPrada M (1990) Effect of selective and reversible MAO inhibitors on dopamine outflow in rat striatum: a microdialysis study. J Neural Transm [Suppl] 32: 79–84

    Google Scholar 

  • Da Prada M, Kettler R, Cesura AM, Richards JG (1988) Reversible, enzyme-activated monoamine oxidase inhibitors: new advances. Pharmacol Res Commun [Suppl] 4: 21–33

    Google Scholar 

  • DaPrada M, Kettler R, Keller NH, Cesura AM, Richards JG, Saura Marti J, Muggli-Maniglio D, Wyss PC, Kyburz E, Imhof R (1990) From moclobemide to Ro 19-6327 and Ro 41-1049: the development of a new class of reversible, selective MAO-A and MAO-B inhibitors. J Neural Transm [Suppl] 29: 279–292

    Google Scholar 

  • Davis TL, Roznoski M, Burns RS (1995) Effects of tolcapone in Parkinson's patients taking L-dihydroxyphenylalanine/carbidopa and selegiline. Mov Disord 10(3): 349–351

    Google Scholar 

  • Demarest KT, Smith DJ, Azzaro AJ (1980) The presence of the type A form of monoamine oxidase within nigrostriatal dopamine-containing neurons. J Pharmacol Exp Ther 215: 461–468

    Google Scholar 

  • Elsworth JD, Sandler M, Lees AJ, Ward C, Stern GM (1982) The contribution of amphetamine metabolites of (−)deprenyl to its antiparkinsonian properties. J Neural Transm 54: 105–110

    Google Scholar 

  • Fowler CJ, Tipton KF (1984) On the substrate specificities of the two forms of monoamine oxidase. J Pharm Pharmacol 36: 111–115

    Google Scholar 

  • Fowler CJ, Oreland L, Marcusson J, Winblad B (1980) Titration of human brain monoamine oxidase A and B by deprenyl and clorgyline. Naunyn Schmiedebergs Arch Pharmacol 311: 263–272

    Google Scholar 

  • Francis A, Pierce LB, Roth JA (1985) Cellular localization of MAO-A and B in brain. Evidence from kainic acid lesions in striatum. Brain Res 334: 59–64

    Google Scholar 

  • Gervas JJ, Muradas V, Bazan E, Aguado BS, de Yebenens JG (1983) Effects of 3-OM-dopa on monoamine metabolism in rat brain. Neurology 33: 278–282

    Google Scholar 

  • Green AR, Mitchell BD, Tordoff AFC, Youdim MBH (1977) Evidence for dopamine deamination of both type A and 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 60: 343–349

    Google Scholar 

  • Guldberg HC, Marsden CA (1975) Catechol-O-methyltransferase: pharmacological aspects and physiological role. Pharmacol Rev 27: 135–206

    Google Scholar 

  • Heikkila RE, Cabbat L, Manzino L, Duviosin RC (1981) Potentiation by deprenyl of L-Dopa induced circling in nigral lesioned rats. Pharmacol Biochem Behav 15: 75–79

    Google Scholar 

  • Hovevey-Sion D, Kopin U, Stull RW, Goldstein DS (1989) Effects of monoamine oxidase inhibitors on levels of catechols and homovanillic acid in striatum and plasma. Neuropharmacology 28: 791–797

    Google Scholar 

  • Johnston JP (1968) Some observations upon a new inhibitor of monoamine oxidase in brain tissue. Biochem Pharmacol 17: 1285–1297

    Google Scholar 

  • Kaakkola S, Wurtman RJ (1993) Effects of catechol-O-methyltransferase inhibitors and L-3,4-dihydroxyphenylalanine with or without carbidopa on extracellular dopamine in rat striatum. J Neurochem 60(1): 137–144

    Google Scholar 

  • Karoum F, Chuang LW, Eisler T, Calne DB, Liebowitz MR, Quitkin FM, Klein DF, Wyatt RJ (1982) Metabolism of (−)deprenyl to amphetamine and metamphetamine may be responsible for deprenyl's therapeutic benefit: a biological assessment. Neurology 32: 503–509

    Google Scholar 

  • Kato T, Dong B, Ishii K, Kinemuchi H (1986) Brain dialysis; in vivo metabolism of dopamine and serotonine by monoamine oxidase A but not by B in the striatum of unrestrained rats. J Neurochem 46: 1277–1282

    Google Scholar 

  • Kelder D, Fagervall I, Fowler CJ, Ross SB (1989) Regulation of the monoamine concentration in the rat brain by intraneuronal monoamine oxidase. Biogen Amines 6: 1–14

    Google Scholar 

  • Knoll J, Magyar K (1972) Some puzzling pharmacological effects of monoamine oxidase inhibitors. Adv Biochem Psychopharmacol 5: 393–408

    Google Scholar 

  • König, JFR, Klippel RA (1963) The rat brain: a stereotaxic atlas of the forebrain and low parts of the brain stem. Williams and Wilkins, Baltimore

    Google Scholar 

  • Levitt P, Pintar JE, Breakefield XO (1982) Immunocytochemical demonstration of monoamine oxidase B in brain astrocytes and serotonergic neurons. Proc Natl Acad Sci USA 79: 6385–6389

    Google Scholar 

  • Limousin P, Pollak P, Gervason-Tournier CL, Hommel M, Perret JE (1993) Ro 40-7592, a COMT inhibitor, plus levodopa in Parkinson's disease. Lancet 341: 1605

    Google Scholar 

  • Linden IB, Nissenen E, Etemadzadeh E, Kaakkola S, Männistö P, Pohto P (1988) Favourable effect of catechol-O-methyltransferase inhibition by OR-462 in experimental model of Parkinson's disease. J Pharmacol Exp Ther 247(1): 289–293

    Google Scholar 

  • Maj J, Rogoz G, Skuza G, Sowinski H, Superata J (1990) Behavioural and neurochemical effects of Ro 40-7592, a new COMT inhibitor with a potential therapeutic activity in Parkinson's disease. J Neural Transm [P-D Sect] 2: 101–112

    Google Scholar 

  • Männistö PT, Toumainen P (1991) Effect of high single doses of levodopa and carbidopa on brain dopamine and its metabolites: modulation by selective inhibitors of monoamine oxidase and/or catechol-O-methyltransferase in the male rat. Naunyn Schmiedebergs Arch Pharmacol 344: 412–418

    Google Scholar 

  • Nissinen E, Linden EB, Schultz E, Kaakkola S, Männistö FT, Pohto P (1988) Inhibition of catechol-O-methyltransferase by two novel disubstituted catechol in the rat. Eur J Pharmacol 153: 263–269

    Google Scholar 

  • Parkinson Study Group (1993) A controlled trial of lazabemide (Ro 19-6327) in untreated Parkinson's disease. Ann Neurol 33: 350–356

    Google Scholar 

  • Parkinson Study Group (1994) A controlled trial of lazabemide (Ro 19-6327) in levodopa treated Parkinson's disease. Arch Neurol 51: 342–347

    Google Scholar 

  • Pieri M, Pieri L, Saner A, Da Prada M, Heavely W (1975) A comparison of drug-induced rotation in rats lesioned in the medial forebrain bundle with 5,6-dihydroxytryptamine or 6-hydroxytryptamine. Arch Int Pharmacol Ther 217(1): 118–130

    Google Scholar 

  • Pieri M, Schaffner R, Pieri L, Da Prada M, Heavily W (1978) Turning in MFB-lesioned rats and antagonism of neuroleptic induced catalepsy after lisuride and LSD. Life Sci 22: 1615–1622

    Google Scholar 

  • Reches A, Fahn S (1982) 3-O-methyldopa blocks dopa metabolism in rat corpus striatum. Ann Neurol 12: 267–271

    Google Scholar 

  • Reynolds JP, Elsworth JD, Blau K, Sandler M, Lees AJ, Stern GM (1978) Deprenyl is metabolized to metamphetamine and amphetamine in man. Br J Clin Pharmacol 6: 543–544

    Google Scholar 

  • Roberts JW, Cora-Locatelli G, Bravi D, Amantea MA, Mouradian MM, Chase TN (1994) Catechol-O-methyltransferase inhibitor tolcapone prolongs levodopa/carbidopa action in parkinsonian patients. Neurology 44: 2685–2688

    Google Scholar 

  • Roth JA, Freor K (1978) Deamination of dopamine and its 3-O-methylated derivative by human brain monoamine oxidase. Biochem Pharmacol 27: 1606–1608

    Google Scholar 

  • Sharpless NN, Meunter MD, Tyce GM, Owen CA (1972) 3-methoxy-4-hydroxyphenylalanine (3-O-methyldopa) in plasma during oral L-DOPA therapy of patients with Parkinson's disease. Clin Chim Acta 37: 359–369

    Google Scholar 

  • Schoepp DD, Azzaro AJ (1981) Specificity of endogenous substrates for types A and B monoamine oxidase in rat striatum. J Neurochem 36: 2025–2031

    Google Scholar 

  • Stenström A, Hardy J, Oreland L (1987) Intra- and extradopamine-synaptosomal localization of monoamine oxidase in striatal homogenates from four species. Biochem Pharmacol 36: 2931–2935

    Google Scholar 

  • Ungerstedt U, Arbuthnott G (1970) Quantitative recording of rotational behavioral in rats after 6-hydroxy-dopamine lesions of the nigro-striatal dopamine system. Brain Res 24: 485–493

    Google Scholar 

  • Wachtel SR, Abercrombie ED (1994) L-3,4-dihydroxyphenylalanine-induced dopamine release in striatum of intact and 6-hydroxydopamine-treated rats: differential effects of monoamine oxidase A and B inhibitors. J Neurochem 63(1): 108–117

    Google Scholar 

  • Wade LA, Katzman R (1975) 3-O-methyldopa uptake and inhibition of L-Dopa at the blood brain barrier. Life Sci 17: 131–136

    Google Scholar 

  • Waldmeier PC, Delini-Stula A, Maitre L (1976) Preferential deamination of dopamine by an A type monoamine oxidase in rat brain. Naunyn Schmiedebergs Arch Pharmacol 292: 9–14

    Google Scholar 

  • Yang HYT, Neff NH (1973) β-phenylethylamine: a specific substrate for type B monoamine oxidase in the brain. J Pharmacol Exp Ther 187: 365–371

    Google Scholar 

  • Yang HYT, Neff NH (1974) The monoamine oxidase of the brain: selective inhibition with drugs and the consequences for the metabolism of biogenic amine. J Pharmacol Exp Ther 189: 733–740

    Google Scholar 

  • Zürcher G, Colzi A, Da Prada M (1990) Ro 40-7592: inhibition of COMT in rat brain an extracerebral tissues. J Neural Transm [Suppl] 32: 375–380

    Google Scholar 

Download references

Author information

Author notes

  1. M. J. Heeringa

    Present address: Department of Medicinal Chemistry, University Center for Pharmacy, Groningen, The Netherlands

Authors and Affiliations

  1. Pharmaceutical Research Department, F. Hoffmann-La Roche & Co. Ltd, Basel, Switzerland

    F. d'Agostini, M. DaPrada & G. Damsma

  2. Department of Medicinal Chemistry, University Center for Pharmacy, Groningen, The Netherlands

    P. DeBoer

Authors
  1. M. J. Heeringa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. d'Agostini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. DeBoer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. DaPrada
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Damsma
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Deceased

Rights and permissions

Reprints and permissions

About this article

Cite this article

Heeringa, M.J., d'Agostini, F., DeBoer, P. et al. Effect of monoamine oxidase A and B and of catechol-O-methyltransferase inhibition on L-DOPA-induced circling behavior. J. Neural Transmission 104, 593–603 (1997). https://doi.org/10.1007/BF01291878

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01291878

Keywords

Search

Navigation