Research Article| Volume 29, ISSUE 1, P15-22, January 01, 1991

Phenylethylaminergic mechanisms in attention-deficit disorder

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      Urinary excretion (24-hr) of β-phenylethylamine (PEA), phenylacetic acid (PAA), phenylalanine (Phe), and p-tyrosine (Tyr), and plasma levels of PAA, Phe, and Tyr were examined in 18 normal children and 26 children diagnosed as having attention-deficit hyperactivity disorder (ADHD). The results indicated that urinary excretion (expressed per g of creatinine) of free and total PEA was significantly lower in the ADHD patients, and plasma levels of Phe and Tyr were also decreased in the ADHD subjects compared with the normal controls.
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        • Baker G.B.
        • Rao T.S.
        • Coutts R.T.
        Electron-capture gas chromatographic analysis of β-phenylethylamine in tissues and body fluids using pentafluorobenzenesulfonyl chloride for derivatization.
        J Chromatogr Biomed Appl. 1986; 381: 211-217
        • Baker G.B.
        • Bieck P.
        • Antonin K.H.
        • Schick C.
        • van Muyden J.
        Urinary increase of β-phenylethylamine and phenylacetic acid in volunteer subjects treated with phenelzine.
        J Neurochem. 1989; 52 (Suppl): S155
        • Bornstein R.A.
        • Baker G.B.
        Neuropsychological correlates of urinary amine metabolites in Tourette's syndrome.
        Int J Neurosci. 1988; 42: 113-120
        • Bornstein R.A.
        • Baker G.B.
        • Carroll A.
        • King G.
        • Ashton S.
        Phenylethylamine metabolism in Tourette's syndrome.
        J Neuropsychiatry Clin Neurosci. 1990; (in press)
        • Boulton A.A.
        Trace amines and the neurosciences: An overview.
        in: Boulton A.A. Baker G.B. Dewhurst W.G. Sandler M. Neurobiology of the Trace Amines. Humana Press, Clifton, NJ1984: 13-24
        • Boulton A.A.
        • Milward L.
        Separation, determination and quantitative analysis of urinary phenylethylamine.
        J Chromatogr. 1971; 57: 187-196
        • Cassens G.
        • Roffman M.
        • Kuruc A.
        • Orsulak P.H.
        • Schildkraut J.J.
        Alterations in brain norepinephrine metabolism induced by environmental stimuli previously paired with inescapable shock.
        Science. 1980; 209: 1138-1139
        • Conners C.K.
        Symptom patterns in hyperkinetic, neurotic, and normal children.
        Child Dev. 1970; 41: 667-682
        • Davis B.A.
        Biogenic amines and their metabolites in body fluids of normal, psychiatric and neurological subjects.
        J Chromatogr. 1989; 466: 89-218
        • DeLisi L.E.
        • Murphy D.L.
        • Karoum F.
        • Mueller E.
        • Targum S.
        • Wyatt R.J.
        Phenylethylamine excretion in depression.
        Psychiatry Res. 1984; 13: 193-201
        • Eriksson T.
        • Carlsson A.
        β-adrenergic control of brain uptake of large neutral amino acids.
        Life Sci. 1988; 42: 1583-1589
        • Fischer E.
        • Heller B.
        • Miró A.H.
        β-phenylethylamine in human urine.
        Arzneim-Forsch. 1968; 18: 1486
        • Fuller N.J.
        • Elia M.
        Factors influencing the production of creatinine: Implications for the determination and interpretation of urinary creatine and creatinine in man.
        Clin Chim Acta. 1988; 175: 199-210
        • Gjerris A.
        • Gjerris F.
        • Soelberg-Sorensen P.
        • et al.
        Do concentrations of neurotransmitters measured in lumbar cerebrospinal fluid reflect the concentration at brain level?.
        Acta Neurochir (Wien). 1988; 91: 55-59
        • Jenner D.A.
        • Harrison G.A.
        • Prior I.A.M.
        • Deonetti D.L.
        • Fujimoto W.Y.
        24-h catecholamine excretion: Relationships with age and weight.
        Clin Chim Acta. 1987; 164: 17-25
        • Karoum F.
        • Potkin S.D.
        • Chuang L.W.
        • Murphy D.L.
        • Liebowitz M.
        • Wyatt R.J.
        Phenylacetic acid excretion in schizophrenia and depression: The origins of PAA in man.
        Biol Psychiatry. 1984; 19: 165-178
        • Karoum F.
        • Torrey E.F.
        • Murphy D.L.
        • Wyatt R.J.
        The origin, drug interaction, urine, plasma and CSF concentration of phenylacetic acid in normal and psychiatric patients.
        in: Boulton A.A. Baker G.B. Dewhurst W.G. Sandler M. Neurobiology of the Trace Amines. Humana Press, Clifton, NJ1984: 457-473
        • Kessler J.A.
        • Gordon E.K.
        • Reid J.L.
        • Kopin I.J.
        Homovanillic acid and 3-methoxy-4-hydroxyphenylethyleneglycol production by the monkey spinal cord.
        J Neurochem. 1976; 26: 1057-1061
        • Khan A.U.
        • Dekirmenjian H.
        Urinary excretion of catecholamine metabolites in hyperkinetic child syndrome.
        Am J Psychiatry. 1981; 138: 108-110
        • Leckman J.F.
        • Maas J.W.
        • Redmond E.J.
        • Heninger G.R.
        Effects of oral clonidine on plasma 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) in man: Preliminary report.
        Life Sci. 1980; 26: 2179-2185
        • Linnoila M.
        • Ninan P.T.
        • Scheinin M.
        • et al.
        Reliability of norepinephrine and major monoamine metabolite measurements in CSF of schizophrenic patients.
        Arch Gen Psychiatry. 1983; 40: 1290-1294
        • Maas J.W.
        • Hattox S.E.
        • Greene N.M.
        • Landis D.H.
        3-Methoxy-4-hydroxyphenylethyleneglycol production by human brain in vivo.
        Science. 1979; 205: 1025-1027
        • Markianos E.
        • Beckmann H.
        Diurnal changes in dopamine β-hydroxylase, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol in serum of man.
        J Neural Transm. 1976; 39: 79-93
        • Pardridge W.M.
        Regulation of amino acid availability to the brain.
        in: Nutrition and the Brain. vol 1. Raven Press, New York1977
        • Philips S.R.
        • Boulton A.A.
        The effects of monoamine oxidase inhibitors on some arylalkylamines in rat striatum.
        J Neurochem. 1979; 33: 159-167
        • Philips S.R.
        • Baker G.B.
        • McKim H.R.
        Effects of tranylcypromine on the concentration of some trace amines in the diencephalon and hippocampus of the rat.
        Experientia. 1980; 36: 241-242
        • Potkin S.G.
        • Karoum F.
        • Chuang L.-W.
        • Cannon-Spoor H.E.
        • Phillips I.
        • Wyatt R.J.
        Phenylethylamine in chronic paranoid schizophrenia.
        Science. 1979; 206: 470-471
        • Raiteri M.
        • del Carmine R.
        • Bertollini A.
        • Levi G.
        Effects of sympathomimetic amines on the synaptosomal transport of noradrenaline, dopamine and 5-hydroxytryptamine.
        Eur J Pharmacol. 1977; 41: 133-143
        • Rogeness G.A.
        • Maas J.W.
        • Javors M.A.
        • Macedo C.A.
        • Fischer C.
        • Harris W.R.
        Attention deficit disorder symptoms and urine catecholamines.
        Psychiatry Res. 1989; 27: 241-251
        • Sabelli H.C.
        • Mosnaim A.D.
        Phenylethylamine hypothesis of affective behaviour.
        Am J Psychiatry. 1974; 131: 695-699
        • Sabelli H.C.
        • Fawcett J.
        • Gusovsky F.
        • et al.
        Clinical studies on the phenylethylamine hypothesis of affective disorder: Urine and blood phenylacetic acid and phenylalanine dietary supplements.
        J Clin Psychiatry. 1986; 47: 66-70
        • Semba J.I.
        • Nankai M.
        • Maruyama Y.
        • Kaneno S.
        • Watanabe A.
        • Takahashi R.
        Increase in urinary β-phenylethylamine preceding the switch from mania to depression: A “rapid cycler”.
        J Nerv Ment Dis. 1988; 176: 116-119
        • Shekim W.O.
        • Javaid J.
        • Dekirmenjian H.
        • Chapel J.L.
        • Davis J.M.
        Effects of d-amphetamine on urinary metabolites of dopamine and norepinephrine in hyperactive boys.
        Am J Psychiatry. 1982; 139: 485-488
        • Shekim W.O.
        • Javaid J.
        • Davis J.M.
        • Bylund D.B.
        Urinary MHPG and HVA excretion in boys with attention deficit disorder and hyperactivity treated with d-amphetamine.
        Biol Psychiatry. 1983; 18: 707-714
        • Szymanski H.V.
        • Naylor E.W.
        • Karoum F.
        Plasma phenylethylamine and phenylalanine in chronic schizophrenic patients.
        Biol Psychiatry. 1987; 22: 194-198
      1. Usdin E. Sandler M. Trace Amines and The Brain. Marcel Dekker, New York1976
        • Wong J.T.F.
        • Baker G.B.
        • Coutts P.T.
        Rapid and simple procedure for the determination of urinary phenylacetic acid using derivatization in aqueous medium followed by electron-capture gas chromatography.
        J Chromatogr Biomed Appl. 1988; 428: 140-146
        • Wood D.R.
        • Reimherr F.W.
        • Wender P.H.
        Treatment of attention deficit disorder with dl-phenylalanine.
        Psychiatry Res. 1985; 16: 21-26
        • Yeung J.M.
        • Baker G.B.
        • Coutts R.T.
        A simple automated gas chromatographic analysis of amino acids and its application to brain tissue and urine.
        J Chromatogr Biomed Appl. 1986; 378: 293-304
        • Yoshimoto S.
        • Kaku H.
        • Shimogawa S.
        • Watanabe A.
        • Nakagawara M.
        • Takahashi R.
        Urinary trace amine excretion and platelet monoamine oxidase activity in schizophrenia.
        Psychiatry Res. 1987; 21: 229-236
        • Yu P.H.
        • Davis B.A.
        • Durden D.A.
        • et al.
        Further studies on platelet monoamine oxidase and penosulfotransferase and plasma levels of acid metabolites in aggressive and non-aggressive prisoners and children with attention deficit disorder.
        in: Boulton A.A. Maitre L. Bieck P.R. Riederer P. Neuropsychopharmacology of the Trace Amines. Humana Press, Clifton, NJ1985
        • Zametkin A.J.
        • Brown G.L.
        • Karoum F.
        • et al.
        Urinary phenylethylamine response to d-amphetamine in 12 boys with attention deficit disorder.
        Am J Psychiatry. 1984; 141: 1055-1058
        • Zametkin A.J.
        • Karoum F.
        • Rapoport J.L.
        • Brown G.L.
        • Wyatt R.J.
        Phenylethylamine excretion in attention deficit disorder.
        J Am Acad Child Psychiatry. 1984; 23: 310-314
        • Zametkin A.J.
        • Rapoport J.L.
        • Murphy D.T.
        • Ismond D.
        Treatment of hyperactive children with monoamine oxidase inhibitors: I. Clinical efficacy.
        Arch Gen Psychiatry. 1985; 42: 962-967
        • Zametkin A.J.
        • Linnoila M.
        • Karoum F.
        • Sallee R.
        Pemoline and urinary excretion of catecholamines and indoleamines in children with attention deficit disorder.
        Am J Psychiatry. 1986; 143: 359-362
        • Zametkin A.J.
        • Karoum F.
        • Ropoport J.L.
        Treatment of hyperactive children with d-phenylalanine.
        Am J Psychiatry. 1987; 144: 792-794