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Effect of alpha-methyl-para-tyrosine on response to cocaine challenge.

Abstract

This study evaluated the effect of an acute reduction in catecholamine synthesis produced by alpha-methyl-para-tyrosine (AMPT), a tyrosine hydroxylase inhibitor, on cocaine-induced euphoria. In a blinded, placebo-controlled study, AMPT (1 g p.o. T.I.D.) was given to 10 non-treatment-seeking cocaine abusers prior to intranasal administration of 2 mg/kg cocaine. AMPT, but not placebo, reduced plasma levels of the dopamine metabolite homovanillic acid and the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol. AMPT also elevated prolactin levels, indicating inhibition of the tuberoinfundibular dopamine system. AMPT pretreatment produced a trend toward diminished cocaine "high" AMPT also tended to lower heart rate and blood pressure responses to cocaine, but had no effect on serum cocaine levels. Although we cannot rule out the therapeutic potential of the depletion strategy, our results with AMPT alone, at this dose, do not strongly support it.

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  • Authors+Show Affiliations

    ,

    Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.

    , , , , ,

    Source

    Biological psychiatry 42:3 1997 Aug 01 pg 181-90

    MeSH

    Administration, Oral
    Adult
    Arousal
    Cocaine
    Diphenhydramine
    Dopamine
    Double-Blind Method
    Enzyme Inhibitors
    Euphoria
    Female
    Homovanillic Acid
    Humans
    Male
    Methoxyhydroxyphenylglycol
    Methyltyrosines
    Middle Aged
    Norepinephrine
    Prolactin
    Substance-Related Disorders
    alpha-Methyltyrosine

    Pub Type(s)

    Clinical Trial
    Comparative Study
    Journal Article
    Randomized Controlled Trial
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    9232210

    Citation

    Stine, S M., et al. "Effect of Alpha-methyl-para-tyrosine On Response to Cocaine Challenge." Biological Psychiatry, vol. 42, no. 3, 1997, pp. 181-90.
    Stine SM, Krystal JH, Petrakis IL, et al. Effect of alpha-methyl-para-tyrosine on response to cocaine challenge. Biol Psychiatry. 1997;42(3):181-90.
    Stine, S. M., Krystal, J. H., Petrakis, I. L., Jatlow, P. I., Heninger, G. R., Kosten, T. R., & Charney, D. S. (1997). Effect of alpha-methyl-para-tyrosine on response to cocaine challenge. Biological Psychiatry, 42(3), pp. 181-90.
    Stine SM, et al. Effect of Alpha-methyl-para-tyrosine On Response to Cocaine Challenge. Biol Psychiatry. 1997 Aug 1;42(3):181-90. PubMed PMID: 9232210.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Effect of alpha-methyl-para-tyrosine on response to cocaine challenge. AU - Stine,S M, AU - Krystal,J H, AU - Petrakis,I L, AU - Jatlow,P I, AU - Heninger,G R, AU - Kosten,T R, AU - Charney,D S, PY - 1997/8/1/pubmed PY - 1997/8/1/medline PY - 1997/8/1/entrez SP - 181 EP - 90 JF - Biological psychiatry JO - Biol. Psychiatry VL - 42 IS - 3 N2 - This study evaluated the effect of an acute reduction in catecholamine synthesis produced by alpha-methyl-para-tyrosine (AMPT), a tyrosine hydroxylase inhibitor, on cocaine-induced euphoria. In a blinded, placebo-controlled study, AMPT (1 g p.o. T.I.D.) was given to 10 non-treatment-seeking cocaine abusers prior to intranasal administration of 2 mg/kg cocaine. AMPT, but not placebo, reduced plasma levels of the dopamine metabolite homovanillic acid and the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol. AMPT also elevated prolactin levels, indicating inhibition of the tuberoinfundibular dopamine system. AMPT pretreatment produced a trend toward diminished cocaine "high" AMPT also tended to lower heart rate and blood pressure responses to cocaine, but had no effect on serum cocaine levels. Although we cannot rule out the therapeutic potential of the depletion strategy, our results with AMPT alone, at this dose, do not strongly support it. SN - 0006-3223 UR - https://www.unboundmedicine.com/medline/citation/9232210/Effect_of_alpha_methyl_para_tyrosine_on_response_to_cocaine_challenge_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006322396003319 DB - PRIME DP - Unbound Medicine ER -