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Preclinical Evaluation of l-Deprenyl: Lack of Amphetamine-Like Abuse Potential

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Inhibitors of Monoamine Oxidase B

Part of the book series: Milestones in Drug Therapy ((MDT))

Abstract

l-Deprenyl is a useful and effective drug in the clinical treatment of parkinsonism and holds promise for treatment of Alzheimer’s disease. However, a recurrent concern with its use has been that it is a phenyl-alkylamine derivative which undergoes metabolic transformation to active compounds with its major metabolites in vivo being l-meth-amphetamine and l-amphetamine [1–3]. As the clinical use of amphetamine-like psychostimulants is limited by their potential for abuse, the question arises as to whether l-deprenyl possesses amphetamine-like abuse liability. Also, the reinforcing effects of cocaine may be mediated by inhibition of dopamine reuptake [4]; l-deprenyl, in addition to its MAO-B actions, also inhibits dopamine reuptake [5, 6]. Therefore, evaluation of l-deprenyl for cocaine-like abuse liability also is a relevant topic of research.

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References

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

    Article  Google Scholar 

  2. Phillips SR. Amphetamine, p-hydroxyamphetamine and ß-phenethylamine in mouse brain and urine after (—)- and (+)-deprenyl administration. J Pharmac Pharmacol 1981; 31: 739–741.

    Article  Google Scholar 

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

    Article  Google Scholar 

  4. Ritz MC, Lamb RJ, Goldberg SR, Kuhar MJ. Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science 1987; 237: 1219–1223.

    Article  Google Scholar 

  5. Knoll J. (-)-Deprenyl (selegiline, Movergan®) facilitates the activity of the nigrostriatal neuron. In: Riederer P, Przuntek J, editors. MAO-B inhibitor selegiline (R-(—)-deprenyl). J Neural Transm 1987; 25: [Supplement] 45–66.

    Google Scholar 

  6. Knoll J. The pharmacology of selegiline ((—)-deprenyl). New aspects. In: Rinne UK, Pakkenberg H, Jensen NO, editors. New strategies in the treatment of Parkinson’s disease. Acta Neurol Scand 1989; 80: [Supplement] 83–91.

    Google Scholar 

  7. Winters WD. The continuum of CNS excitatory states and hallucinosis. In: Siegel RK, West W, editors. Hallucinations: behavior, experience and theory. New York: Wiley 1975: 53–75.

    Google Scholar 

  8. Hermann WM. Development and critical evaluation of an objective procedure for the electroencephalographic classification of psychotropic drugs. In: Hermann WM, editor. Electroencephalography in drug research. Stuttgart: Gustav Fischer 1982: 249–351.

    Google Scholar 

  9. Itil TM, editor. Psychotropic drugs and the human EEG. Vol. 8. Modern problems in pharmacopsychiatry. Basel: Karger 1974.

    Google Scholar 

  10. Serafetinides EA, Willis BA. A method for quantifying EEG for psychopharmacological research. Int Pharmacopsychiatry 1973; 8: 245–247.

    Google Scholar 

  11. Saphiro DM, Glasser M. Measurement and comparison of EEG drug effects. In: Itil TM, editor. Psychotropic drugs and human EEG. Vol. 8. Modern problems in pharmacopsychiatry. Basel: Karger 1974: 327–349.

    Google Scholar 

  12. Lukas SF. Brain electrical activity as a tool for studying drugs of abuse. In: Mello NK, editor. Advances in substance abuse. Behavioral and biological research. Vol. 4. London: Jessica Kingsley Publishers 1991: 1–88.

    Google Scholar 

  13. Fink M. EEG and human psychopharmacology. Ann Rev Pharmacol 1969; 9: 241–258.

    Article  Google Scholar 

  14. Fink M, Saphiro DM, Itil TM. EEG profiles of fenfluramine, amobarbital and dextroamphetamine in normal volunteers. Psychopharmacologia 1971; 22: 369–383.

    Article  Google Scholar 

  15. Nickel B, Schulze G, Szelenyi I. Effect of enantiomers of deprenyl (selegiline) and amphetamine on physical abuse liability and cortical electrical activity in rats. Neuropharmacology 1990; 29: 983–992.

    Article  Google Scholar 

  16. Dietsch G. Fourier-Analyse von Elektroencephalographologrammen des Menschen. Pflugers Arch Ges Physiol 1932; 230: 106–112.

    Article  Google Scholar 

  17. Nickel B, Zerrahn H. Pharmacoelectroencephalography in the rat as a method for characterization of different types of analgesics. Postgrad Med J 1987; 63: [Supplement] 3: 45–47.

    Article  Google Scholar 

  18. Nickel B, Szelenyi I. Comparison of changes in the EEG of freely moving rats induced by enciprazine, buspirone and diazepam. Neuropharmacology 1989; 28: 799–803.

    Article  Google Scholar 

  19. Hosoya E. Screening of dependence liability of drugs using rats. Pharmac Ther 1979; 5: 515–517.

    Article  Google Scholar 

  20. Blasig I, Herz H, Reinhold K, Zieglgansberger S. Development of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats. Psychopharmacologia 1973; 33: 19–38.

    Article  Google Scholar 

  21. Goldberg SR, Stolerman IP, editors. Behavioral analysis of drug dependence. London: Academic Press 1986.

    Google Scholar 

  22. Skinner BF, editor. The behavior of organisms. New York: Appleton-Century-Crofts 1938.

    Google Scholar 

  23. Ferster CB, Skinner BF, editors. Schedules of Reinforcement. New York: Appleton-Century-Crofts 1957.

    Google Scholar 

  24. Skinner BF. Two types of conditioned reflex: a reply to Konorski and Miller. J Gen Psyehol 1937; 16: 272–279.

    Article  Google Scholar 

  25. Terrace HS. Stimulus control. In: Honig WK, editor. Operant behavior: areas of research and application. Englewood Cliffs, N.J.: Prentice-Hall 1966: 271–344.

    Google Scholar 

  26. Young R, Glennon RA. Discriminative stimulus properties of amphetamine and structurally related phenylalkylamines. Med Res Rev 1986; 6: 99–130.

    Article  Google Scholar 

  27. Young AM. Discriminative stimulus profiles of psychoactive drugs. In: Mello NK, editor. Advances in substance abuse. Behavioral and biological research. Vol. 4. London: Jessica Kingsley Publishers 1991: 139–203.

    Google Scholar 

  28. Schechter MD. Stimulus properties of ¿l-amphetamine as compared to l-amphetamine. Eur J Pharmacol 1978; 47: 461–464.

    Article  Google Scholar 

  29. Glennon R, Young R. Further investigation of the discriminative stimulus properties of MDA. Pharmacol Biochem Behav 1984; 20: 501–505.

    Article  Google Scholar 

  30. Yasar S, Schindler CW, Cohen C, Thorndike EB, Goldberg SR, Szelenyi I. Drug discrimination analysis of l-deprenyl. 21st annual Meeting; 1991 November 10–15; New Orleans (LA), USA. Society for Neuroscience Abstracts 1991; 17: 1431.

    Google Scholar 

  31. Yang HYT, Neff NH. Beta-phenylethylamine. A specific substrate for type B monoamine oxidase of brain. J Pharmacol Exp Ther 1973; 187: 365–371.

    Google Scholar 

  32. Yang HYT, Neff NH. The monoamine oxidases of brain: Selective inhibition with drugs and the consequences for the metabolism of the biogenic amines. J Pharmacol Exp Ther 1974; 189: 733–740.

    Google Scholar 

  33. Colpaert FC, Niemegeers CJE, Janssen PAJ. Evidence that preferred substrate for type B monoamine oxidase mediates stimulus properties of MAO inhibitors: a possible role for beta-phenylethylamine in the cocaine cue. Pharm Biochem Behav 1980; 13: 513–517.

    Article  Google Scholar 

  34. Johanson CE, Barrett JE. The discriminative stimulus effects of cocaine in pigeons. American College of Neuropsychopharmacology. 29th Annual Meeting; 1990 Dec. 10–14; San Juan, Puerto Rico.

    Google Scholar 

  35. Heinionen EH, Myllyla V, Sotaniemi K, Lamintausta R, Salonem JS, Anttila M, et al. Pharmacokinetics and metabolism of selegiline. In: Rinne UK, Pakkenberg H, Jenssen NO, editors. New strategies in the treatment of Parkinson’s disease. Acta Neurol Scand 1989; 80: [Supplement] 126: 83–91.

    Google Scholar 

  36. Porsolt RD, Pawelec C, Jalfre M. Use of a drug discrimination procedure to detect amphetamine-like effects of antidepressants. In: Colpaert FC, Slangen JL, editors. Drug discrimination: applications in CNS pharmacology. Amsterdam: Elsevier, Biomedical 1982: 193–202.

    Google Scholar 

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

    Article  Google Scholar 

  38. Moser PC. Generalization of l-deprenyl, but not MDL-72974, to the amphetamine stimulus in rats. Psychopharmacol 1990; 101: S40.

    Google Scholar 

  39. Kornetsky C, Bain G. Brain-stimulation reward: A model for drug-induced euphoria. In: Adler M, Cowan A, editors. Testing and evaluation of drugs of abuse. Vol. 6. Modern methods in pharmacology. New York: Wiley-Liss 1990: 211–231.

    Google Scholar 

  40. Gallistel CR, Karaas D. Pimozide and amphetamine have opposite effects on the reward summation function. Pharmacol Biochem Behav 1984; 20: 73–77.

    Article  Google Scholar 

  41. O’Regan D, Kwok RPS, Yu PH, Bailey BA, Greenshaw AJ, Boulton AA. A behavioral and neurochemical analysis of chronic and selective monoamine oxidase inhibition. Psychopharmacologia 1987; 92: 42–47.

    Article  Google Scholar 

  42. Aulakh CS, Cohen RM, Pradhan SN, Murphy DL. Self-stimulation responses are altered following long-term but not short-term treatment with clorgyline. Brain Res 1983; 270: 383–386.

    Article  Google Scholar 

  43. Deneau GA, Yanagita T, Seevers MH. Self-administration of psychoactive substances by the monkey. A measure of psychological dependence. Psychopharmacologia 1969; 16: 30–48.

    Article  Google Scholar 

  44. Schuster CR, Johanson CE. The use of animal models for the study of drug abuse. In: Gibbins RJ, Israel Y, Kalant H, Popham R, Schmidt W, Smart R, editors. Research advances in alcohol and drug problems. Vol. 1. New York: Wiley and Sons 1974: 1–31.

    Google Scholar 

  45. Schuster CR, Thompson T. Self-administration of and behavioral dependence on drugs. Ann Rev of Pharmacol 1969; 9: 483–502.

    Article  Google Scholar 

  46. Winger G, Palmer RK, Woods JH. Drug-reinforced responding: rapid determination of dose-response functions. Drug and Alcohol Dependence 1989; 24: 135–142.

    Article  Google Scholar 

  47. Timar J, Knoll B. The effect of repeated administration of (—)-deprenyl on the phenylethylamine-induced stereotypy in rats. Arch Int Pharmacodyn 1986; 279: 50–60.

    Google Scholar 

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Authors
  1. S. Yasar
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  2. G. Winger
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  3. B. Nickel
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  4. G. Schulze
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  5. S. R. Goldberg
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Editor information

Editors and Affiliations

  1. Dept. of Pharmacology, ASTA Medica AG, Weismüllerstrasse 45, D-6000, Frankfurt/Main 1, Germany

    I. Szelenyi

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© 1993 Springer Basel AG

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Yasar, S., Winger, G., Nickel, B., Schulze, G., Goldberg, S.R. (1993). Preclinical Evaluation of l-Deprenyl: Lack of Amphetamine-Like Abuse Potential. In: Szelenyi, I. (eds) Inhibitors of Monoamine Oxidase B. Milestones in Drug Therapy. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-6348-3_11

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  • DOI: https://doi.org/10.1007/978-3-0348-6348-3_11

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-6349-0

  • Online ISBN: 978-3-0348-6348-3

  • eBook Packages: Springer Book Archive

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