Skip to main content
SpringerLink
Log in

The functional consequences of inhibition of monoamine oxidase type B: comparison of the pharmacological properties ofl-deprenyl and MDL 72145

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

  1. 1.

    The pharmacological properties of two selective inhibitors of monoamine oxidase (MAO) type B,l-deprenyl and MDL 72145 [(E)-2-(3,4-dimethyoxyphenyl)-3-fluoroallylamine, HCl], have been investigated in rats and mice in relation to their effects on MAO.

  2. 2.

    Selective inhibition of MAO B achieved following 18 h pretreatment withl-deprenyl and/or MDL 72145 did not per se lead to prominent pharmacological activity; no effects were seen in the mouse “Behavioural Despair” test, hypothermia induced by reserpine in mice was neither prevented nor reversed and there was no change in the cardiovascular responsiveness of the pithed rat to tyramine, noradrenaline or stimulation of the spinal sympathetic outflow.

  3. 3.

    l-Deprenyl differed from MDL 72145 in that short term treatment with this drug caused positive effects in the “Behavioural Despair” test, reversal of reserpine hypothermia, indirect sympathomimetic stimulation of blood pressure and heart rate in the pithed rat and ipsilateral rotation in rats with unilateral nigro-striatal lesions. Qualitatively similar effects were seen with dexamphetamine.

  4. 4.

    The marked difference between the pharmacological effects of MDL 72145 andl-deprenyl despite equivalent inhibition of MAO B suggests that many of the pharmacological actions ofl-deprenyl result from its amphetaminelike sympathomimetic properties. MDL 72145 can, therefore, be considered a more reliable tool with which to explore the functional importance of MAO B inhibition in experimental animals and man.

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

  • Bey P, Fozard J, Lacoste JM, McDonald JA, Zreika M, Palfreyman MG (1984a) (E)-2-3,4-dimethoxyphenyl)-3-fluoroallylamine: a selective, enzyme-activated inhibitor of type B monoamine oxidase. J Med Chem 27:9–10

    Google Scholar 

  • Bey P, Fozard J, McDonald IA, Palfreyman MG, Zreika M (1984b) MDL 72145: a potent and selective inhibitor of MAO type B. Br J Pharmacol 81:50P

  • Blackwell B (1981) Adverse effects of antidepressant drugs. Part I: Monoamine oxidase inhibitors and tricyclics. Drugs 21:201–219

    Google Scholar 

  • Birkmayer W, Riederer P, Youdim MBH (1982) (−)Deprenyl in the treatment of Parkinson's Disease. Clin Neuropharmacology 5:195–230

    Google Scholar 

  • Caramona MM (1982) Monoamine oxidase of types A and B in the saphenous vein and mesenteric artery of the dog. Naunyn-Schmiedeberg's Arch Pharmacol 319:121–124

    Google Scholar 

  • Denes B, Greef K (1984) Investigations on the mechanism of positive inotropic action of (+)-tranylcypromine in isolated guineapig atria. Arzneimittelforschung 34:266–270

    Google Scholar 

  • Elsworth JD, Glover V, Reynolds GP, Sandler M, Lees AJ, Phuadradit P, Shaw KM, Stern GM, Kumar P (1978) Deprenyl administration in man: a selective monoamine oxidase inhibitor without the cheese effect. Psychopharmacology 57:33–38

    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 

  • Finberg JPM, Tenne M (1982) Relationship between tyramine potentiation and selective inhibition of monoamine oxidase types A and B in the rat vas deferens. Br J Pharmacol 77:13–21

    Google Scholar 

  • Fowler CJ (1982) Selective inhibitors of monoamine oxidase types A and B and their clinical usefulness. Drugs of the Future 7:501–517

    Google Scholar 

  • Fowler CJ, Ross SB (1984) Selective inhibitors of monoamine oxidase A and B: Biochemical, pharmacological and clinical properties. Med Res Rev 4:323–358

    Google Scholar 

  • Fozard JR, Spedding M, Palfreyman MG, Wagner J, Möhring J, Koch-Weser J (1980) Depression of sympathetic nervous function bydl-α-monofluoromethyldopa, an enzyme-activated, irreversible inhibitor ofl-aromatic amino acid decarboxylase. J Cardiovasc Pharmacol 2:229–245

    Google Scholar 

  • Fozard JR, Palfreyman MG, Zreika M (1984) The comparative pharmacology of two selective inhibitors of monoamine oxidase B: Deprenyl and MDL 72145. Br J Pharmacol 82:309P

  • Gillespie JS, Muir TC (1967) A method of stimulating the complete sympathetic outflow from spinal cord to the blood vessels in the pithed rat. Br J Pharmacol 30:78–87

    Google Scholar 

  • Heikkila RE, Cabbat FS, Manzino L, Duvoisin RC (1981) Potentiation by deprenyl ofl-dopa induced circling in nigral-lesioned rats. Pharmac Biochem Behav 15:75–79

    Google Scholar 

  • Jaffe JH (1980) Drug addition and drug abuse. In: Gilman AG, Goodman LS, Gilman A (eds) The pharmacological basis of therapeutics, 6th edn. Macmillan, New York, pp 535–584

    Google Scholar 

  • Jalfre M, Bucher B, Coston A, Mocquet G, Porsolt RD (1982) Neuropharmacological profile of MD 780515, a new reversible inhibitor of type A monoamine oxidase. Arch Int Pharmacodyn Ther 259:194–221

    Google Scholar 

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

    Google Scholar 

  • Karoum F, Chuang L-W, Eisler TMS, Calnc DB, Leibowitz MR, Quitkin FR, Klein DF, Wyatt RJ (1982) Metabolism of (−)deprenyl to amphetamine and methamphetamine may be responsible for deprenyl's therapeutic benefit: a biochemical assessment. Neurology 32:503–509

    Google Scholar 

  • Knoll J (1979) (−)Deprenyl — the MAO inhibitor without the “cheese effect”. Trends Neurol Sci 2:111–113

    Google Scholar 

  • Knoll J (1983) Deprenyl (selegiline): the history of its development and pharmacological action. Acta Neurol Scand 68 (Suppl 95): 57–80

    Google Scholar 

  • Knoll J, Magyar K (1972) Some pharmacological effects of monoamine oxidase inhibitors. In: Coste E, Sandler M (eds) Monoamine oxidases — new vistas. Raven Press, New York pp 393–408

    Google Scholar 

  • Koulu M, Lammintansta R (1981) Effects ofl-deprenyl on human growth hormone secretion. J Neural Transm 51:223–231

    Google Scholar 

  • Lancet Editorial (1982) Deprenyl in Parkinson's Disease. Lancet (ii):695–696

  • Lavie P, Wajsbort J, Youdim MBH (1980) Deprenyl does not cause insomnia in parkinsonian patients. Comm Psychopharmacol 4:303–307

    Google Scholar 

  • McDonald I, Lacoste JM, Bey P, Palfreyman MG, Zreika M (1985) Enzyme-activated irreversible inhibitors of monoamine oxidase: phenylallylamine structure-activity relationships. J Med Chem 28:186–193

    Google Scholar 

  • Neff NH, Goridis C (1972) Neuronal monoamine oxidase: specific enzyme types and their rate of formation. Adv Biochem Psychopharmacol 5:307–323

    Google Scholar 

  • Palfreyman MG, Zreika M, McDonald I, Fozard JR, Bey P (1983) MDL 72145, an irreversible inhibitor of MAO B. L'encephale 9, Suppl 1:A3

    Google Scholar 

  • Philips SR (1981) Amphetamine, p-hydroxyamphetamine and β-phenethylamine in mouse brain and urine after (−)- and (+)-deprenyl administration. J Pharmac Pharmacol 31:739–741

    Google Scholar 

  • Porsolt RD, Bertin A, Jalfre M (1977) Behavioural despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229:327–336

    Google Scholar 

  • Porsolt RD, Pawelec C, Roux S, Jalfre M (1984) Discrimination of the amphetamine cue. Effects of A, B and mixed type inhibitors of monoamine oxidase. Neuropharmacol 23:569–573

    Google Scholar 

  • Reynolds GP, Elsworth JD, Blau K, Sandler M, Lees AJ, Stern GM (1978) Deprenyl is metabolized to methamphetamine and amphetamine in man. Br J Clin Pharmacol 6:542–544

    Google Scholar 

  • Riederer P, Reynolds GP, Jellinger K (1984) The pharmacology of Parkinson's disease:l-dopa and beyond. Trends Pharmacol Sci 5:25–27

    Google Scholar 

  • Robin M, Forler C, Palfreyman MG (1985) Effect of chronic apomorphine on the development of denervation supersensitivity. Pharmacol Biochem Behav 22:547–551

    Google Scholar 

  • Simpson LL (1978) Evidence that deprenyl, a type B monoamine oxidase inhibitor, is an indirectly acting sympathomimetic amine. Biochem Pharmacol 27:1591–1595

    Google Scholar 

  • Thornton C, Dore CJ, Elsworth JD, Herbert M, Stern GM (1980) The effect of deprenyl, a selective monoamine oxidase B inhibitor, on sleep and mood in man. Psychopharmacol 70:163–166

    Google Scholar 

  • Ungerstedt U (1971) Postsynaptic supersensitivity after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system in the rat brain. Acta Physiol Scand (Suppl) 367:69–93

    Google Scholar 

  • Zreika M, McDonald IA, Bey P, Palfreyman MG (1984) MDL 72145, an enzyme-activated irreversible inhibitor with selectivity for monoamine oxidase type B. J Neurochem 43:448–454

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Merrell-Dow Research Institute, 16 rue d'Ankara, F-67084, Strasbourg Cedex, France

    John R. Fozard, Monique Zreika, Marc Robin & Michael G. Palfreyman

Authors
  1. John R. Fozard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Monique Zreika
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marc Robin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael G. Palfreyman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fozard, J.R., Zreika, M., Robin, M. et al. The functional consequences of inhibition of monoamine oxidase type B: comparison of the pharmacological properties ofl-deprenyl and MDL 72145. Naunyn-Schmiedeberg's Arch. Pharmacol. 331, 186–193 (1985). https://doi.org/10.1007/BF00634237

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00634237

Key words

Search

Navigation