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“In vitro” effect of some 5-hydroxy-indolalkylamine derivatives on monoamine uptake system

  • J. A. Morón
  • V. Perez
  • E. Fernández-Alvarez
  • J. L. Marco
  • M. Unzeta
Part of the Journal of Neural Transmission. Supplement book series (NEURAL SUPPL, volume 52)

Summary

Three different indolalkylamine derivatives (FA 102, FA 69, FA 70) having in common an -OH group at 5 position of the indole ring and differing in the presence of a methyl group at the N or the acetylenic group of the side chain, have been synthesized and assayed as monoamine oxidaseA (MAO-A) [E.C.1.4.3.4] inhibitors. They were effective inhibitors with, in some cases, similar potencies to clorgyline. “In vitro” experiments were performed on rat brain synaptosomes to investigate whether these MAO-A inhibitors had any effect on noradrenaline (NA), dopamine (DA) and 5hydroxytryptamine (5-HT) transport systems in different rat brain regions. The effect of these drugs were compared with those of clorgyline and 1deprenyl. FA 102, FA 69, FA 70 behaved as inhibitors of 3H-monoamine uptake with similar rank of order of potency for amine uptake inhibition: 5-HT > DA > NA. The IC50 values for FA 102, FA 69, FA 70, respectively, were: 17 μM, 60 μM, 18 μM for 5HT uptake in cortex and 37 μM, 55 μM and 20 μM in hippocampus; 70 μM, 385 μM, 695 μM for NA uptake in cortex and 315 μM, 255 μM and 600 μM in hypothalamus; 270 μM, 160 μM, 40 μM for DA uptake in striatum. l-Deprenyl was a very poor inhibitor of monoamine uptake, whereas clorgyline behaved similarly to these indolalkylamine derivatives. Comparing these results with the IC50 values of Citalopram, nisoxetine and GBR12909, specific and selective inhibitors of 5-HT, NA and DA transport systems respectively, indicated that these indolalkylamine derivatives interact more strongly with the 5HT uptake system.

Keywords

Indole Ring Krebs Buffer Parkinson Study Group Monoamine Uptake Acetylenic Group 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Bradford HJ (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254PubMedCrossRefGoogle Scholar
  2. Cruces MA, Elorriaga D, Fernández-Alvarez E, Prieto O (1988) Synthesis and biochemical properties of N-acetylenic and N-allenic derivatives of 2-aminemethylindoles as selective inhibitors of monoamine oxidase. Pharmacol Res Commun 20: 102–107CrossRefGoogle Scholar
  3. Dodd PR, Hardy JA, Dakley AE, Edwarson JA, Perry EK, Dalaunoy JP (1981) A rapid method for preparing synaptosomes: comparison with alternative procedures. Brain Res 226: 107–118PubMedCrossRefGoogle Scholar
  4. Fang J, Yu PH (1994) Effect of l-deprenyl, its structural analogues and some monoamine oxidase inhibitors on monoamine uptake. Neuropharmacol 33: 763–768CrossRefGoogle Scholar
  5. Murphy DL, Aulakh CS, Garrick NA, Sunderland T (1987) Monoamine oxidase inhibitors as antidepressants; implications for the mechanism of action of antidepressants and psychobiology of the affective disorders and some related disorders. In: Meltzer H (ed) Psychopharmacology: the third generation of progress. Raven Press, New York, pp 545–552.Google Scholar
  6. The Parkinson Study Group (1989) Effect of deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med 321: 1364CrossRefGoogle Scholar
  7. Schildkraut JJ (1965) The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry 122: 509–522PubMedGoogle Scholar
  8. Valtier D, Dement WC, Mignot E (1992) Monoaminergic uptake in synaptosomes prepared from frozen brain tissue samples of normal and narcoleptic canines. Brain Res 588: 115–119PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1998

Authors and Affiliations

  • J. A. Morón
    • 1
  • V. Perez
    • 1
  • E. Fernández-Alvarez
    • 2
  • J. L. Marco
    • 2
  • M. Unzeta
    • 1
    • 1
  1. 1.Departament de Bioquímica i Biologia MolecularUniversitat Autonoma de BarcelonaBellatera (Barcelona)Spain
  2. 2.Departament de Química OrgánicaC.S.I.C.MadridSpain

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