Baker GB, Bornstein RA, Rouget AC, Ashton SE, van Muyden JC,
Phenylethylaminergic mechanisms in attention-deficit disorder.
Psychiatry 1991 Jan 1;29(1):15-22
"Urinary excretion (24-hr) of beta-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
Matsuishi T, Yamashita Y.
and neurotransmitter studies in patients with learning disabilities]
To Hattatsu 1999 May;31(3):245-8
"To clarify the pathophysiology of learning
disability (LD), we measured the urinary levels of 3-methoxy-4-hydroxyphenyl glycol
(MHPG), and phenylethylamine (PEA) in urine samples collected in a 24 hour period.
Findings were compared with those obtained in age-matched controls and diseased
controls including patients with attention deficit-hyperactivity disorder (ADHD),
infantile autism, and mental retardation. The mean urinary level of MHPG in LD
(n = 6) were not significantly different from those in ADHD (n = 16), mental retardation
(n = 4), infantile autism (n = 5), and the controls (n = 6), while the mean urinary
levels of PEA were significantly lower in LD (n = 6, 91 +/- 17.3 micrograms/mg)
and in ADHD (n = 5, 65 +/- 53.6 micrograms/mg) as compared to age-matched controls
(n = 3, 340 +/- 264.5 micrograms/mg) ANOVA, (p < 0.05). PEA is considered to
play an important role for the pathogenesis of LD and ADHD." [Abstract]
[Decreased beta-phenylethylamine in urine of children with attention
deficit hyperactivity disorder and autistic disorder]
To Hattatsu 2002 May;34(3):243-8
"beta-phenylethylamine (PEA), a biogenic
trace amine, acts as a neuromodulator in the nigrostriatal dopaminergic pathway
and stimulates the release of dopamine. To clarify the mechanism of neurochemical
metabolism in attention deficit hyperactivity disorder (ADHD), we measured the
urine levels of PEA using gas chromatography-chemical ionization-mass spectrometry.
The urinary levels of 3-methoxy-4-hydroxyphenyl glycol (MHPG), homovanillic acid
(HVA), and 5-hydroxy-indoleacetic acid (5-HIAA) were determined by high performance
liquid chromatography. Urine samples were collected in a 24 hour period. Findings
were compared with those obtained from controls (N = 15), children with ADHD (N
= 15), and children with autistic disorder (AD) (N = 5). The mean urinary levels
of MHPG, HVA, and 5-HIAA in the children with ADHD were not significantly different
from those of the controls or those with AD, whereas PEA levels were significantly
lower in children with ADHD (11.23 +/- 13.40 micrograms/g creatinine) compared
with controls (56.01 +/- 52.18 micrograms/g creatinine)." [Abstract]
Zametkin AJ, Karoum F, Linnoila M, Rapoport JL,
Brown GL, Chuang LW, Wyatt RJ.
Stimulants, urinary catecholamines,
and indoleamines in hyperactivity. A comparison of methylphenidate and dextroamphetamine.
Gen Psychiatry 1985 Mar;42(3):251-5
"Children with attention deficit disorder
with hyperactivity were given either methylphenidate hydrochloride or dextroamphetamine
sulfate to compare the effects on urinary excretion of catecholamines, indoleamines,
and phenylethylamine (PEA). Methylphenidate's effects were distinctly different
from those of dextroamphetamine. After methylphenidate administration, both norepinephrine
(NE) and normetanephrine (NMN) concentrations were significantly elevated, and
there was a 22% increase in excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG).
In contrast, after dextroamphetamine treatment, MHPG excretion was significantly
reduced and NE and NMN values were unchanged. Excretion of dopamine and metabolites
was unchanged by either drug. Urinary PEA excretion was not significantly changed
after methylphenidate treatment, but increased 1,600% in response to dextroamphetamine.
Methylphenidate treatment did not significantly alter serotonin or 5-hydroxyindoleacetic
acid excretion. Effects of dextroamphetamine were not tested." [Abstract]
A, Yamashita Y, Koeda T, Hiratani M, Kaneko M, Yamada S, Matsuishi T.
urine phenylethylamine after methylphenidate treatment in children with ADHD.
Neurol 2002 Sep;52(3):372-4
"The urine levels of beta-phenylethylamine,
3-methoxy-4-hydroxyphenyl glycol, homovanillic acid, and 5-hydroxyindoleacetic
acid were measured to clarify the neurochemical mechanism in attention deficit
hyperactivity disorder. beta-Phenylethylamine levels were significantly lower
in attention deficit hyperactivity disorder individuals (n = 37) than in controls
(n = 21). The 22 children with attention deficit hyperactivity disorder were treated
with methylphenidate, and they were further divided into methylphenidate responders
(n = 18) and nonresponders (n = 4). beta-Phenylethylamine levels significantly
increased after methylphenidate therapy in responders, whereas they did not increase
in nonresponders." [Abstract]
Niddam R, Arbilla S, Baud P, Langer SZ.
beta-phenylethylamine but not [3H](+)-amphetamine is released by electrical stimulation
from perfused rat striatal slices.
Eur J Pharmacol 1985
"Perfused rat striatal slices were prelabelled with
either [3H](+)-amphetamine or [3H] beta-phenylethylamine. Electrical stimulation
released a significant amount of radioactivity only from the slices prelabelled
with [3H] beta-phenylethylamine. The electrically evoked release of radioactivity
from slices labelled with [3H] beta-phenylethylamine was entirely calcium-dependent
and was abolished after pretreatment with reserpine (5 mg/kg s.c., 24 h). In addition,
S-sulpiride (1 microM), which facilitates the electrically evoked release of radioactivity
from slices labelled with [3H]DA by blocking dopamine autoreceptors, also induced
an increase of the radioactivity released by electrical stimulation from slices
labelled with [3H] beta-phenylethylamine. Our results indicate that, in spite
of the structural similarities between AMPH and PEA, only the latter which is
the naturally occurring analog of AMPH can be released by electrical stimulation
in a calcium-dependent manner." [Abstract]
MY, Juorio AV, Paterson IA, Boulton AA.
Regulation of aromatic L-amino
acid decarboxylase by dopamine receptors in the rat brain.
Neurochem 1992 Feb;58(2):636-41
"Decarboxylation of phenylalanine by aromatic
L-amino acid decarboxylase (AADC) is the rate-limiting step in the synthesis of
2-phenylethylamine (PE), a putative modulator of dopamine transmission. Because
neuroleptics increase the rate of accumulation of striatal PE, these studies were
performed to determine whether this effect may be mediated by a change in AADC
activity. Administration of the D1 antagonist SCH 23390 at doses of 0.01-1 mg/kg
significantly increased rat striatal AADC activity in an in vitro assay (by 16-33%).
Pimozide, a D2-receptor antagonist, when given at doses of 0.01-3 mg/kg, also
increased AADC activity in the rat striatum (by 25-41%). In addition, pimozide
at doses of 0.3 and 1 mg/kg increased AADC activity in the nucleus accumbens (by
33% and 45%) and at doses of 0.1, 0.3, and 1 mg/kg increased AADC activity in
the olfactory tubercles (by 23%, 30%, and 28%, respectively). Analysis of the
enzyme kinetics indicated that the Vmax increased with little change in the Km
with L-3,4-dihydroxyphenylalanine as substrate. The AADC activity in the striatum
showed a time-dependent response after the administration of SCH 23390 and pimozide:
the activity was increased within 30 min and the increases lasted 2-4 h. Inhibition
of protein synthesis by cycloheximide (10 mg/kg, 0.5 h) had no effect on the striatal
AADC activity or on the increases in striatal AADC activity produced by pimozide
or SCH 23390. The results indicate that the increases in AADC activity induced
by dopamine-receptor blockers are not due to de novo synthesis of the enzyme."
S, Neff NH, Hadjiconstantinou M.
Regulation of tyrosine hydroxylase
and aromatic L-amino acid decarboxylase by dopaminergic drugs.
J Pharmacol 1997 Apr 4;323(2-3):149-57
"We provide evidence that dopamine
receptors differentially modulate tyrosine hydroxylase and aromatic L-amino acid
decarboxylase in the mouse striatum. The dopamine D1 receptor family (D1-like)
antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benazepine
(SCH 23390), elevated aromatic L-amino acid decarboxylase activity and protein
content in striatum, as well as the mRNA for the enzyme in midbrain. The dopamine
D1-like receptor agonist, (+/-)-1-phenyl-2,3,4,5-tetrahydro-(1 H)-3-benzazepine-7,8-diol
(SKF 38393), had no effect on aromatic L-amino acid decarboxylase. The dopamine
D1-like drugs had no effect on tyrosine hydroxylase. In contrast, the dopamine
D2 receptor family (D2-like) antagonists haloperidol and spiperone elevated both
tyrosine hydroxylase and aromatic L-amino acid decarboxylase activities. The increase
in aromatic L-amino acid decarboxylase activity was accompanied by elevated enzyme
protein content but not mRNA. The dopamine D2-like receptor agonists, bromocriptine,
quinpirole and (+/-)-7-hydroxydipropylaminotetralin (7-OH-DPAT), all decreased
striatal tyrosine hydroxylase. Under the conditions used, bromocriptine and 7-OH-DPAT,
but not quinpirole, decreased aromatic L-amino acid decarboxylase activity of
striatum. Both the dopamine D1- and D2-like receptor antagonists enhanced the
turnover of striatal dopamine to differing degrees, as judged by the ratio of
acid metabolites of dopamine to dopamine. Taken together our results indicate
that aromatic L-amino acid decarboxylase can be modulated independently of tyrosine