Effects of N-propargyl-1-(R)aminoindan (rasagiline) in models of motor and cognition disorders

  • Z. Speiser
  • R. Levy
  • S. Cohen
Part of the Journal of Neural Transmission. Supplement book series (NEURAL SUPPL, volume 52)


N-propargyl-1-(R)aminoindan (rasagiline) is a new and selective irreversible MAO-B inhibitor, currently being considered as the mesylate salt for potential therapy in certain neurological disorders. It has been studied in animal models of cognition and motor dysfunction. Its ability to restore normal motor activity was determined in models of acute drug-induced dopaminergic dysfunction: Its effects in improving cognition and memory deficits was studied in adult and senescent rats that had been exposed to prolonged hypoxia, then subjected to the passive and active avoidance tests. In a-methylp-tyrosine (α-MpT)-induced hypokinesia (100–120mg/kg, i.p.) pretreatment with rasagiline at 2.5 mg/kg i.p. restored motor activity to control level. But pretreatment with reserpine abolished the protective effect of rasagiline. Rasagiline at 0.5mg/kg/day was protective against α-MpT also in hypoxialesioned rats. In haloperidol-induced catalepsy in rats (1.5 mg/kg, s.c.) or mice (4–6mg/kg s.c.), rasagiline improved recovery of normal locomotion, gait and coordination at 0.4–2.4mg/kg i.p. and 1.8–15mg/kg i.p., respectively. In amphetamine-induced stereotypy (0.6mg/kg s.c), rasagiline potentiated this effect at 1.5 mg/kg i.p. In hypoxia-induced impairment of memory and learning, rasagiline at 0.32–0.5 mg/kg/day per os improved performance of adult rats in passive and active avoidance, and of senescent rats in active avoidance. Selegiline was either ineffective or less effective at equivalent doses. Racemic N-propargyl-1-aminoindan (AGN-1135), besides being of lower potency, had a different dose-dependency than rasagiline in antagonizing haloperidolinduced catalepsy or α-MpT-induced hypokinesia. l-(R)aminoindan ((R)AI), a metabolite of rasagiline, in relatively high doses produced effects that were distinct in certain respects from those of rasagiline.


Active Avoidance Prolonged Hypoxia Monoamine Oxidase Type Cognition Disorder Active Avoidance Test 


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  1. Engberg G, Elebring Th, Nissbrandt H (1991) Deprenyl (selegiline), a selective MAO-B inhibitor with active metabolites; effects on locomotor activity, dopaminergic neurotransmission and firing rate of nigral dopamine neurons. J Pharmacol Exp Ther 259: 841–847PubMedGoogle Scholar
  2. Finberg J, Youdim MBH (1985) Modification of blood pressure and nictitating membrane response to sympathetic amines by selective monoamine oxidase inhibitors, types A and B, in the cat. Br J Pharmacol 85: 541–546PubMedCrossRefGoogle Scholar
  3. Finberg JPM, Tenne M, Youdim MBH (1981) Tyramine antagonistic properties of AGN-1135, an irreversible inhibitor of monoamine oxidase type B. Br J Pharmacol 73:65–74PubMedCrossRefGoogle Scholar
  4. Fowler CJ, Callingham BA, Mantle TJ, Tipton KF (1980) The effect of lipophilic compounds upon the activity of rat liver mitochondrial monoamine oxidase A and B. Biochem Pharmacol 29: 1177–1183PubMedCrossRefGoogle Scholar
  5. Gelowitz DL, Richardson JS, Wishart ThB, Yu PH, Lai C-T (1994) Chronic L-deprenyl or L-amphetamine: equal cognitive enhancement, unequal MAO inhibition. 47: 41–45PubMedGoogle Scholar
  6. Heikkila RE, Davoisin JP, Finberg J, Youdim MBH (1985) Prevention of MPTP-induced neurotoxicity by AGN-1133 and AGN-1135, selective inhibitors of monoamine oxidase-B. Eur J Pharmacol 116: 313–317PubMedCrossRefGoogle Scholar
  7. Herrera AJ, Machado A, Cano J (1993) Ageing and monoamine turnover in the lateral geniculate and visual cortex of the rat. Neurochem Int 22: 531–539PubMedCrossRefGoogle Scholar
  8. Horn AS, Snyder SH (1972) Steric requirements for catecholamine uptake by rat brain synaptosomes: studies with rigid analogs of amphetamine. J Pharmacol Exp Ther 180: 523–530PubMedGoogle Scholar
  9. Izquierdo I (1992) Dopamine receptors in the caudate nucleus and memory processes. Trends Pharmacol Sci 13: 7–8PubMedCrossRefGoogle Scholar
  10. Kalir A, Sabbagh A, Youdim MBH (1981) Selective acetylenic “suicide” and reversible inhibitors of monoamine oxidases types A and B. Br J Pharmacol 73: 55–64PubMedCrossRefGoogle Scholar
  11. Lamensdorf I, Youdim MBH, Finberg JPM (1995) Increase in striatal dopamine following chronic selective inhibition of MAO A or B. Isr J Med Sci 31: 739Google Scholar
  12. McCullough LD, Sokolowsky JD, Solomone JD (1993) A neurochemical and behavioral investigation of the involvement of nucleus accumbens dopamine in instrumental avoidance. Neurosci 52: 919–925CrossRefGoogle Scholar
  13. Nilsson OG, Leanza G, Björklund A (1992) Acetylcholine release in the hippocampus: regulation by monoaminergic afferents as assessed by in vivo microdialysis. Brain Res 584: 132–140PubMedCrossRefGoogle Scholar
  14. Riederer P, Youdim MBH (1986) Monoamine oxidase activity and monoamine metabolism in brains of parkinsonian patients treated with l-deprenyl. J Neurochem 46: 1359–1365PubMedCrossRefGoogle Scholar
  15. Speiser Z, Amitzi-Sonder J, Gitter S, Cohen S (1988) Behavioral differences in the developing rat, following postnatal anoxia or postnatally-injected AF-64A, a cholinergic neurotoxin. 30: 89–94PubMedGoogle Scholar
  16. Speiser Z, Reicher S, Gitter S, Cohen S (1989) Tacrine or arecoline mediates reversal of anoxia-or AF-64A-induced behavioural disorders in the developing rat. Neuro-pharmacol 28: 1325–1332Google Scholar
  17. Speiser Z, Amitzi-Zonder J, Ashkenazi R, Gitter S, Cohen S (1990) Central catechola-minergic dysfunction and behavioral disorders following hypoxia in adult rats. Behav Brain Res 37: 19–27PubMedCrossRefGoogle Scholar
  18. Skuza G, Rogoz Z, Quack G, Danysz W (1994) Memantine, anmantadine and L-deprenyl potentiate the action of L-Dopa in monoamine-depleted rats. J Neural Transm 98: 57–67CrossRefGoogle Scholar
  19. Wesnes (1990) Potential of moclobemide to improve cerebral insufficiency identified using a scopolamine model of aging and dementia. Acta Psychiatr Scand [Suppl] 360: 71–72CrossRefGoogle Scholar
  20. Youdim MBH, Finberg JPM, Levy R, Sterling J, Lerner D, Berger-Paskin T, Yellin H (1995) R-Enantiomers of N-propargyl-aminoindan compounds. Their preparation and pharmaceutical compositions containing them. United States Patent 5, 457, 133Google Scholar
  21. Zornetzer, ST (1985) Catecholamine system involvement in age related memory dysfunction. Ann NY Acad Sci 444: 242–254PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1998

Authors and Affiliations

  • Z. Speiser
    • 1
    • 3
  • R. Levy
    • 2
  • S. Cohen
    • 1
  1. 1.Department of Physiology and PharmacologyTel Aviv UniversityKiryat NordauIsrael
  2. 2.Corporate R&D DivisionTeva Pharmaceutical Industries, Ltd.Kiryat NordauIsrael
  3. 3.Department of Physiology and PharmacologyTel Aviv UniversityTel AvivIsrael

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