_L-DOPA Cyclohexyl Ester Is a Novel Potent and Relatively Stable Competitive Antagonist Against _L-DOPA Among Several _L-DOPA Ester Compounds

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Author(s)

Abstract

We explored L−DOPA esters with chemically bulky structures to find a potent stable competitive antagonist against L−DOPA, compared to DOPA methyl ester(DOPA ME).In anesthetized rats, DOPA cyclohexyl ester(DOPA CHE), DOPA cyclopentyl ester(DOPA CPE)and DOPA cyclopentyldimethyl ester(DOPA CPDME)at 1μg microinjected into depressor sites of the nucleus tractus solitarii elicited or tended to elicit more marked antagonism against depressor responses to 60 ng L−DOPA, compard to DOPA ME.At 100 ng, DOPA CHE elicited the most potent antagonism.At 1μg, duration of the antagonistic activity of DOPA CHE was approximately three times longer than that of DOPA ME.During microdialysis of the nucleus accumbens, conversion from DOPA CHE at 1μM perfused via probes to extracellular L−DOPA was the lowest among these compounds and less than one half of that from DOPA ME.Binding studies showed that the recognition site for L−DOPA differs from ionotropic glutamatergic, dopaminergic D<SUB>1</SUB> and D<SUB>2</SUB> receptors.We recently found that L−DOPA evoked by transient ischemia may act as a DOPA CHE−sensitive causal factor for glutamate release and resultant neuronal cell death.DOPA CHE is the most potent, relatively stable competitive antagonist against L−DOPA and is a useful mother compound to develop neuroprotective drugs.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 82(1), 40-47, 2000-01-01

    The Japanese Pharmacological Society

References:  41

Cited by:  1

Codes

  • NII Article ID (NAID)
    10008182629
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4966447
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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