The Contribution of cocoa additive to cigarette smoking addiction

RIVM report 650270002 Page 113 of 207
Tryptamine
which is mediated by the peripheral serotonin (5-HT2) receptor (25). Another study
showed a tryptamine induced apparent increase of serum insulin level in mice,
mediated also by the same serotonin receptor (16).
Critical assessment
Tryptamine is a neurotransmitter or a modulator of neurotransmission. Tryptamine
produces pharmacological effects in man that are similar to LSD and other tryptamine
derivatives. Such effects are tachypnea, tachycardia, behavioral changes and
hallucinations. Experiments with rats showed that tryptamine evoke effects, which
are related with the serotonin receptors. It has a biphasic effect on the arterial tone,
induces acquisition deficits, hypothermia and anorectic effect and affected the
glucose plasma level. The tryptamine dose used to show these effects were in the
range of 1 µg (i.c.v.) (22) and 5 mg/kg body weight (ipr.) (21). However, no data are
available on tryptamine pharmacological effects by respiratory studies. It is not clear
whether the estimated potential tryptamine dose in cigarette (1000 µg/day) exerts any
respiratory effects, as only data are available via other routes.
Conclusion
No conclusion can be made whether the tryptamine dose in cigarettes is high enough
to exert any systemic pharmacological effects. The (longterm) effects of tryptamine
or its pyrolysis/combustion products on the pulmonary system are unknown and need
further study.
PHARMACOKINETICS
Absorption
No data are available on absorption through the respiratory and gastrointestinal
system.
Bioavailability
No data are available on the oral and respiratory bioavailability.
Oral tryptamine administration seems to be inactive, due to deamination by
monoamine oxidase (26).
Distribution
Tryptamine is found in the brain, liver, kidney and other tissues (12).
Human platelets show an active and saturable uptake of serotonin and tryptamine.
The uptake of both substrates appears to be mediated by the same carrier (27).
metabolism
The major route of catabolism for tryptamine is one of enzymatic inactivation.
Sequentional action by monoamine oxidase and aldehyde dehydrogenase results into
formation to indole-3-acetic acid (IAA) via indole acetaldehyde. It has been shown
that this pathway produces 70 % of IAA. A minor portion of the aldehyde is reduced
to indole-3-ethanolamine by aldehyde reductase. N-methyltransferase, has been
shown to exist in human brain, lung and blood and is linked to the formation of
hallucinogenic N-methyl and N,N-dimethyl derivatives of tryptamine. In addition to
methylation of tryptamine, this enzyme is also linked to the formation of harmalan
derivatives (a condensed product of tryptamine with aldehydes) (12). Tryptamine
metabolism is sensitive to changes in brain tryptophan. This is especially apparent