The Contribution of cocoa additive to cigarette smoking addiction

Page 148 of 207 RIVM report 650270002
Phenylethylamine
depletion by reserpine or by blockade of the amine pump by imipramine (16).
Other
Critical assessment
Phenylethylamine is classified as a neuromodulator of dopaminergic and possibly
serotonergic and noradrenergic synapses. Phenylethylamine produced a
bronchoconstriction of isolated perfused lungs of guinea-pig. No data are available on
phenylethylamine inhalation effects in human. Therefore it is unknown whether the
phenylethylamine dose in cigarette will exert a bronchoconstrictory effect.
Phenylethylamine exerts both positive inotropic and vasoconstrictory effects in dogs.
Phenylethylamine tended to produce an initial tachycardia followed by a bradycardia
in dogs. Phenylethylamine has amphetamine-like effects in rats including
symphatomimetic effects, increasing nonspecific motoractivity, exploratory behavior,
steoreotypic behavior, electrophysiological alerting, reinforcement of complex
sesquences behavior and anorectic effects. It is suggested that endogenous
phenylethylamine may contribute to the antidepressant, stimulant, or euphoriant
effects of several drugs. Phenylethylamine exerts its CNS effect at high doses or
when the MAO is inhibited. Based on the current CNS data, it is unknown whether
the phenylethylamine dose in cigarette is enough to exert any CNS effect.
Conclusion
Not enough data are available on inhalation effects of phenylethylamine on the
pulmonary system in human. Therefore, it is unknown whether the phenylethylamine
dose in cigarettes (estimated 12.1 mg/day/25 cigarettes) will affect the pulmonary
system. The (longterm) effects of phenylethylamine or its pyrolysis/combustion
products on the pulmonary system are also unknown and need further study.
PHARMACOKINETICS
Absorption
In-vitro studies with perfused lungs of rats and rabbits have shown that a large
portion of the exposed phenylethylamine (95 %) is transported rapidly through the
pulmonary endothelium. No data were available on the absorption through the alveoli
epithelium (21, 22).
Bioavailability
No data are available on bioavailability through the gastro-intestinal and pulmonary
system. Although a high portion of phenylethylamine is absorbed through the
pulmonary endothelium (95 %), it is rapidly neutralised by the pulmonary
monoamine oxidase enzymes and consequently the bioavailability through the
mentioned system is reduced. Intake of MAO-inhibitors will increase the
bioavailability of phenylethylamine (21-23).
Distribution
Phenylethylamine is heterogenously distributed in various brain regions of human.
Total tissue levels are low (< 10 ng/g tissue), compared with other biogenic amines
(which range from 100 to 5000 ng/g tissue), probably because of poor storage and
rapid turnover rate (half-life 5 – 10 min) (16). When radioactively labelled 14 C-