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1,2,3,4-Tetrahydro-2-methyl-4,6,7-isoquinolinetriol inhibits tyrosine hydroxylase activity in rat striatal synaptosomes

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Summary

1,2,3,4-tetrahydro-2-methyl-4,6,7-isoquinolinetriol (TMIQ), a tetrahydroisoquinoline derivate of adrenaline, was tested for potency as an analog of the dopamine depleting agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in assays of tyrosine hydroxylase (TH) activity in the striatal synaptosome preparation. TMIQ inhibited TH activity with an IC50 (4 × 10−6M) similar to that found for MPTP (IC50 1 × 10−6M). TH inhibitions produced by IC50 concentrations of TMIQ were reversed by monoamine oxidase (MAO)-A or MAO-B inhibitors (clorgyline or deprenyl), or the dopamine reuptake blocker nomifensine, or excess cofactor (6R)-5,6,7,8-tetrahydro-L-biopterin. TMIQ did not appear to act at the presynaptic D2 sulpiride sensitive autoreceptor for dopamine synthesis modulation. Thesein vitro data are consistent with earlier findings that TMIQ acts as a dopamine depleting agent, and with the possibility that TMIQ may have a degree of MPTP-like activityin vivo.

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  1. O. Phillipson

    Present address: Department of Anatomy, School of Medical Sciences, University of Bristol, UK

Authors and Affiliations

  1. Department of Anatomy, School of Medical Sciences, University of Bristol, UK

    J. Liptrot

  2. Department of Pharmacology, School of Medical Sciences, University of Bristol, UK

    D. Holdup

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Liptrot, J., Holdup, D. & Phillipson, O. 1,2,3,4-Tetrahydro-2-methyl-4,6,7-isoquinolinetriol inhibits tyrosine hydroxylase activity in rat striatal synaptosomes. J. Neural Transmission 96, 51–62 (1994). https://doi.org/10.1007/BF01277928

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  • DOI: https://doi.org/10.1007/BF01277928

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