약학회지 (YAKHAK HOEJI)

  • 제43권1호
  • /
  • Pages.33-41
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  • 1999
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  • 0377-9556(pISSN)
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  • 2383-9457(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

6-하이드록시도파민으로 유도된 흰주 뇌내의 도파민 고갈에 대한 $\ell$-디프레닐의 억제효과

${\ell}-Deprenyl$ (Selegiline) Prevents 6-Hydroxydopamine-induced Depletion of Dopamine and Its Metabolites in Rat Brain

  • 발행 : 1999.02.01
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초록

Whereas as selective inhibitor of monoamine oxidase type B, ${\ell}-deprenyl$ (selegiline), is now widely used in the treatment of Parkinson's disease, the precise action mechanism of the drug remains elusive. In this study, to investigate protective effect of ${\ell}-deprenyl$ against the dopamine depletion induced by 6-hydroxydopamine (6-OHDA), the changes in tissue contents of dopamine, serotonine (5-HT) and their metabolites by ${\ell}-deprenyl$ were examined in intact and 6-OHDA-lesioned rat brain. In intact rats, a single intraperitoneal (i.p.) administration of ${\ell}-deprenyl$ showed a no change in striatal dopamine and its metabolites at low concentrations (0.25 and 1 mg/kg), but significantly inhibited dopamine metabolism at a higher concentration (10 mg/kg). The repeated administration of ${\ell}-deprenyl$ (0.25 and 1 mg/kg, i.p., for 21 consecutive days) reduced the contents of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) in dose-dependent manners without changes in dopamine content. Bilateral intracerebroventricular (i.c.v) infusion of 6-OHDA ($100{\;}\mu\textrm{g}/10{\;}{\mu}{\ell}/hemisphere$) depleted dopamine in striatum and septum by 81% and 90% respectively. When rats were pretreated with ${\ell}-deprenyl$ before 6-OHDA administration, the striatal and septal dopamine levels were significantly increased by about 3.0-fold and 3.4-fold, respectively, compared to the untreated 6-OHDA-lesioned rat. Pretreatment of ${\ell}-deprenyl$ also significantly enhanced the dopmaine metabolites, DOPAC, HVA and 3-methoxytyramine, in the striatum, and DOPAC in the septum. These results indicate that a ${\ell}-deprenyl$ pretreatment prevents 6-OHDA-induced depletion of striatal dopamine and its metabolites.

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참고문헌

  1. Basic & Clinical pharmacology (6th ed.) Katzung, B. G.
  2. Adv. Biochem. Psychopharmacol. v.5 Some puzzling pharmacological effects of monoamine oxidase inhibitors Knoll, j.;Magyar, K.
  3. Eur. J. Pharmacol. v.226 The molecular pharmacology of L-deprenyl Gerlach, M.;Riederer, P.;Youdim, M. B. H.
  4. Nature v.265 Dopamine is a monoamine oxidase B substrate in man Glover, V.;Sandler, M.;Owen, F.;Riley, G. J.
  5. Acta Neurol Scand v.84 no.suppl 136 A review of the pharmacology of selegiline Heinonen, E. H.;Lammintausta, R.
  6. J. Pharmacol. Exp. Ther. v.189 The monoamine oxidase of brain:selective inhibition with druges and the consequences for the metabolism of the biogenic amines Yang, H. Y.;T.;Neff, N. H.
  7. European Journal of Pharmacology v.163 Chronic L-deprenyl-induced up-re-gulation of dopamine uptake carrier Wiener, H. L.;Hashim, A.;Lajtha, A.;Sershen, H.
  8. Life Sciences v.48 Deprenyl induced activities of both superoxide dismutase & catalase but not of glutathione peroxidase in the striatum of young male rat Carrillo, M. C.;Kanai, S.;Nokubo, M.;Kitani, K.
  9. British journal of pharmacology v.117 Protection of aged sudstantia nigra of the rat against oxidative damage by(-)-deprenyl. Cruz, C. P.;Revilla, E.;Steffen, V.;Rodriguez-Gomez, J. A.;Cano, J.;Machado, A.
  10. Neurosci. Lett. v.224 (-)-Deprenyl protection of 1-methyl-4-phenylpyridium ion (MPP+)-induced apoptosis independent of MAO-B inhibition Le, W.;Jankovic, J.;Xie, W.;Kong, R.;Appel, S. H.
  11. J. Neural. Transm., suppl v.49 Apoptosis in neurodegenerative disorders: potential for therapy by modifying gene transcription Tatton, W. G.;Chalmers-Redman, B. M. E.;Ju, W. Y. H.;Wadia, J.;Tatton, N. A.
  12. J. Neural. Transm. suppl v.41 Is selegiline neuroprotective in Parkinson's disease? Gerlach, M.;Youdim, M. B. H.;Riederer, P.
  13. J. Neuroch. v.63 (-)-Deprenyl reduces PC12 cell apoptosis by inducign new protein synthesis Tatton, W.G.;Ju, W. Y. L.;Holland, D. P.;Tai, C.;Kwan, M.
  14. J. Neural. Transm. suppl v.48 (-)-Deprenyl reduces neuronal apoptosis and facilitates neuronal outgrowth by altering protein synthesis without inhibiting monoamine oxidase Tatton, W. G.;Wadia, J. S.;AChalmer-Redman, R. M. E.;Tatton, N. A.
  15. Neurochem. Res. v.19 The effects of monoamine oxidase B inhibition in dopamine metabolism in rats with nigro-striatal lesions sCARR, E.;Wingerchuck, D. M.;Juorio, A. V.;Paterson, I. A.
  16. J. Neurochem v.65 Influence of selective inhibition of monoamine oxidase A or B on striatal metabolism of L-DOPA in hemiparkinsonian rats Finberg, J. P. M.;Wang, J.;Goldstein, D. S.;Kopin, I. J.;Bankiewics, K. S.
  17. Int. Rev. Neurol v.31 Animal models of parkinsornism using selective neurotoxins: clinical and basic implications Zigmond, M. J.;Stricker, E.
  18. J. Pharmcol. Exp. Ther. v.174 Effect of 6-hydroxydopamine on brain morepinephrine and dopamine: Evidence for selective degeneration of catecholamine neurons Breese, G.;Traylor, T. D.
  19. J. Biol. Chem. v.193 Protein measurement with the Folin phenol reagent Lowry, O. H.;Rosebrough, N. J.;Farr, A. L.;Randall, R. J.
  20. Br. J. Pharmacol. v.34 Evidence that dopamine deamination by both type A and type B monoamine oxidase in rat brain in vivo and for the degree of enzyme inhibition necessary to increase functional activity of dopamine and 5-hydroxytryptamine Green, A. R.;Mitchell, B.;Tordorff, A.
  21. Biochem Pharmacol. v.24 Mechanism of action of 6-hydroxyhopamine Sachs, C.;Jonsson, G.
  22. J. Neural. Transm. v.77 Variabillity among brain regions in the specificity of 6-hydroxydopamine (6-OHDA)-induced lesions Commins, D. L.;Shaughnessy, R. A.;Axt, K. J.;Vosmer, G.;Seiden, L. S.
  23. J. Neural Transm. v.22 no.SUP. The pharmacology of (-)-deprenyl Knoll, J.