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The effect of presynaptic catecholamine depletion on 6-hydroxymelatonin sulfate: a double blind study of alpha-methyl-para-tyrosine.

Abstract

Because it is a competitive inhibitor of tyrosine hydroxylase, alpha-methyl-para-tyrosine (AMPT) is used to study psychiatric disorders. Melatonin serves as a biological marker of catecholamine function since its secretion is regulated by noradrenergic neurons via beta-adrenergic receptors in the pineal gland. Ten healthy volunteers were administered AMPT in a double-blind placebo controlled study. When subjects received AMPT, nocturnal 6-hydroxymelatonin sulfate (6-SM) decreased significantly as compared with promethazine (night 1 P=0.002; and night 2 P=0.001). Urinary MHPG also decreased on both study days (DF1,9 F=9.82, GG=0.0121). Nocturnal 6-SM excretion and melatonin secretion correlated highly (r=0.91, P=0.0007). Behavioral ratings did not reveal a difference in symptomatology and did not correlate with changes in 6-SM or MHPG. This study demonstrates in healthy controls that 6-SM reliably reflects presynaptic catecholamine depletion induced by AMPT without the emergence of behavioral symptoms.

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  • Authors+Show Affiliations

    ,

    Department of Psychiatry and Psychology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.

    , , , ,

    Source

    MeSH

    Adult
    Area Under Curve
    Catecholamines
    Cross-Over Studies
    Double-Blind Method
    Enzyme Inhibitors
    Female
    Humans
    Male
    Melatonin
    Norepinephrine
    Receptors, Presynaptic
    Tyrosine 3-Monooxygenase
    alpha-Methyltyrosine

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    10082229

    Citation

    Krahn, L E., et al. "The Effect of Presynaptic Catecholamine Depletion On 6-hydroxymelatonin Sulfate: a Double Blind Study of Alpha-methyl-para-tyrosine." European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, vol. 9, no. 1-2, 1999, pp. 61-6.
    Krahn LE, Lin SC, Klee GG, et al. The effect of presynaptic catecholamine depletion on 6-hydroxymelatonin sulfate: a double blind study of alpha-methyl-para-tyrosine. Eur Neuropsychopharmacol. 1999;9(1-2):61-6.
    Krahn, L. E., Lin, S. C., Klee, G. G., Lu, P. Y., Ory, S. J., & Zimmermann, R. C. (1999). The effect of presynaptic catecholamine depletion on 6-hydroxymelatonin sulfate: a double blind study of alpha-methyl-para-tyrosine. European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, 9(1-2), pp. 61-6.
    Krahn LE, et al. The Effect of Presynaptic Catecholamine Depletion On 6-hydroxymelatonin Sulfate: a Double Blind Study of Alpha-methyl-para-tyrosine. Eur Neuropsychopharmacol. 1999;9(1-2):61-6. PubMed PMID: 10082229.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The effect of presynaptic catecholamine depletion on 6-hydroxymelatonin sulfate: a double blind study of alpha-methyl-para-tyrosine. AU - Krahn,L E, AU - Lin,S C, AU - Klee,G G, AU - Lu,P Y, AU - Ory,S J, AU - Zimmermann,R C, PY - 1999/3/19/pubmed PY - 1999/3/19/medline PY - 1999/3/19/entrez SP - 61 EP - 6 JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JO - Eur Neuropsychopharmacol VL - 9 IS - 1-2 N2 - Because it is a competitive inhibitor of tyrosine hydroxylase, alpha-methyl-para-tyrosine (AMPT) is used to study psychiatric disorders. Melatonin serves as a biological marker of catecholamine function since its secretion is regulated by noradrenergic neurons via beta-adrenergic receptors in the pineal gland. Ten healthy volunteers were administered AMPT in a double-blind placebo controlled study. When subjects received AMPT, nocturnal 6-hydroxymelatonin sulfate (6-SM) decreased significantly as compared with promethazine (night 1 P=0.002; and night 2 P=0.001). Urinary MHPG also decreased on both study days (DF1,9 F=9.82, GG=0.0121). Nocturnal 6-SM excretion and melatonin secretion correlated highly (r=0.91, P=0.0007). Behavioral ratings did not reveal a difference in symptomatology and did not correlate with changes in 6-SM or MHPG. This study demonstrates in healthy controls that 6-SM reliably reflects presynaptic catecholamine depletion induced by AMPT without the emergence of behavioral symptoms. SN - 0924-977X UR - https://www.unboundmedicine.com/medline/citation/10082229/The_effect_of_presynaptic_catecholamine_depletion_on_6_hydroxymelatonin_sulfate:_a_double_blind_study_of_alpha_methyl_para_tyrosine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-977X(98)00006-6 DB - PRIME DP - Unbound Medicine ER -