The Contribution of cocoa additive to cigarette smoking addiction

RIVM report 650270002 Page 149 of 207
Phenylethylamine
phenylethylamine was injected intravenously in rat, radioactivity was measured in all
tissues, including the brain. Its clearance from these tissues and from brain regions
was very fast (24). Phenylethylamine has been found also in various mouse tissues:
the highest concentrations were found in the small intestine, followed by the blood
and liver. Concentrations of approximately of 5 ng/g wet weight were detected in
brain tissue, which increased after inhibition of monoamine oxidase by pargyline
(25). Phenylethylamine is highly lipid-soluble and readily crosses the blood-brain
barrier. Blood-borne phenylethylamine is accumulated by the brain against a
concentration gradient. Brain and peripheral phenylethylamine are in dynamic
equilibrium (16, 26).
Metabolism
In the nervous tissue, phenylethylamine is synthesized by decarboxylation of
phenylalanine, a reaction that is catalyzed by the enzyme aromatic L-amino acid
decarboxylase. Phenylethylamine is metabolized by MAO, primarily by type-B (and
to a small extent MAO-A), and aldehyde dehydrogenase to phenylacetic acid, which
is the major metabolite of phenylethylamine in the brain. The regional distribution of
phenylacetic acid in the brain coincides with that of phenylethylamine. Exogenous
phenylethylamine in humans is primarily metabolized to phenylacetic acid.
Approximately 10% of brain phenylethylamine is also metabolized to
phenylethanolamine by dopamine-ß-hydroxylase. Phenylethanolamine is present in
human brain and animal brain and may function as a cotransmitter in norepinephrine
synapses (11, 16).
Monoamine oxidase is responsible for the pulmonary metabolism of
phenylethylamine. In a study the effects of treatment of rats with the tricyclic
antidepressant desmethylimipramine (DMI) on the disposition of phenylethylamine in
isolated perfused rat lungs was investigated. DMI accumulation in the lung reached a
plateau after 6 days of treatment with mean values of 1.1, 6.1, and 315 nmol/lung at
dose levels of 0.67, 6.7, and 33 mumol/kg/day, respectively. During a 10-min
perfusion at a concentration of 10 -6 M phenylethylamine was rapidly taken up and
extensively metabolized by lungs from control animals. Phenylethylamine clearance
in perfused lung was decreased in a dose-related manner by DMI treatment with a
corresponding decrease in its metabolism. In efflux experiments, unmetabolized
phenylethylamine was only found in the perfusate from lungs of DMI-treated rats. It
was concluded that phenylethylamine clearance after DMI treatment results almost
entirely from inhibition of pulmonary MAO (21).
Inactivation of phenylethylamine was studied in a preparation of rabbit lung perfused
with Krebs physiological medium at 37 ºC. Percentage removal was high with
phenylethylamine (95%). Inactivation of phenylethylamine could be accounted for by
metabolic degradation to deaminated products, which appeared in lung effluent
within 90 s of the beginning of amine perfusion. When intrapulmonary metabolism of
phenylethylamine was inhibited by simultaneous perfusion with semicarbazide (10
mM) and pargyline (10 µM), the removal rate was unaltered, establishing that uptake
of the amine from the vascular space is not dependent on metabolism at least for 4
min infusions (22).
Excretion
Phenylethylamine is excreted in the urine. Oral ingestion of phenylethylamine