The Contribution of cocoa additive to cigarette smoking addiction

Page 150 of 207 RIVM report 650270002
Phenylethylamine
increased the urinary excretion of phenylacetic acid and mandelic acid (27-29).
Kinetic parameters
Phenylethylamine crosses the blood-brain barrier easily and its concentration in the
brain after peripheral injection peaks within 5 minutes and returns to normal level
within 30 min. The turnover of endogenous phenylethylamine in the brain is high
with a half-life of 0.4 min (11).
Critical assessment
In-vitro studies have shown that phenylethylamine is rapidly absorbed by the
pulmonary endothelial tissue and is also rapidly inactivated by pulmonary MAO.
When radioactively labelled 14 C-phenylethylamine was injected intravenously in rat,
radioactivity was measured in all tissues, including the brain. Phenylethylamine
crosses the blood-brain barrier easily and its concentration in the brain after
peripheral injection peaks within 5 minutes and returns to normal level within 30 min.
The turnover of endogenous phenylethylamine in the brain is high with a half-life of
0.4 min. 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. Based on in-vitro kinetic data of
phenylethylamine, the pulmonary MAO will reduce the phenylethylamine intake
through cigarette smoking.
Conclusion
There are no in-vivo pharmacokinetic data available on respiratory intake of
phenylethylamine. Based on the in-vitro data, probably pulmonary MAO will reduce
the bioavailability of phenylethylamine through cigarette smoking.
TOXICOLOGY
Acute toxicity
Human
The effect of 5 mg phenylethylamine in apple juice on 27 healthy volunteers was
studied using a randomized placebo-controlled double-blind procedure.
Phenylethylamine produced symptoms like headache, dizziness and discomfort in
some volunteers (30).
Animal
LD50 oral mouse 400 mg/kg (1)
LDLo oral rat 800 mg/kg (1)
LD50 subcutaneous mouse 320 mg/kg (1)
LD50 intravenous mouse 100 mg/kg (1)
LDLo intraperitoneal rat 100 mg/kg (1)
In one study, stereotyped sniffing behaviour together with forepaw padding -defined
as the phenylethylamine syndrome- was induced by MAO-B inhibitors in rats
injected with 30 mg/kg i.p. phenylethylamine. The comparison of the abilities of the
MAO-B inhibitors to induce the syndrome and to inhibit MAO-B in rat brain
homogenates indicated that at least 75% of MAO-B activity in rat brain had to be
inhibited to induce the phenylethylamine syndrome. A good correlation was found
between the abilities of MAO-B inhibitors to induce the behavioral syndrome and to