The Contribution of cocoa additive to cigarette smoking addiction

RIVM report 650270002 Page 117 of 207
Tryptamine
analogous reaction (43).
Tryptamines and ß-carbolines are two classes of psychoactive indoles found in plants
and animals (44). ß -carboline alkaloids are derived as a result of condensation
between indoleamine (e.g. tryptamine) and short-chain carboxylic acid (e.g. pyruvic
acid) or aldehyde (e.g. acetaldehyde), a reaction that occurs readily at room
temperature. These compounds have been found endogenously in human and animal
tissues and may be formed as a byproduct of a secondary metabolisation (45). Also
exogenous aldehydes in may react with tryptamine to form ß-carbolines. When
human saliva obtained after cigarette smoking was incubated in the presence of
tryptamine, the formation of 1,2,3,4-tetrahydro-ß-carboline (TBC) and 1-methyl-
1,2,3,4-tetrahydro-ß-carboline (MTBC) was observed in a short time. After
incubation with tryptamine (2.5 µg/ml) for 10 min, the concentrations of TBC and
MTBC formed were 3.27 and 0.35 ng/ml, respectively. The analysis of cigarette
smoke solution and immersion solutions of denture-base acrylic resins showed that
ng- µg/ml levels of formaldehyde and acetaldehyde were contained in cigarette
smoke and leached from dental resins. These results indicate that both precursors,
tryptamine and aldehydes, coexist in oral environments and that their interaction to
form TBC and MTBC potentially occurs in human saliva without participation of
salivary enzyme (46).
When tryptamine was injected into the paraventricular nucleus of the hypothalamus
after pretreatment with a monoamineoxidase inhibitor or with serotonin, it induced an
anorectic effect. This effect may be due to a prolongation of the activity of serotonin
resulting from tryptamine competing with serotonin for the same reuptake system
(24).
The sequential injection of the dopamine and serotonin receptor agonists,
apomorphine and tryptamine, in rats at time intervals with minimal direct behavioral
interference, was used to observe response changes with respect to a single challenge.
When tryptamine was preceded by an apomorphine challenge the effective doses of
the serotonin (5-HT2) antagonists ritanserin and risperidone for 50% inhibition of the
seizures increased by a factor of 2.5. When apomorphine was preceded by a
tryptamine challenge, the total agitation score of the control animals increased by
59% on the average. Mutual enhancement of tryptamine and apomorphine appears to
occur even at a time when the behavioral effects of the first agonist are no longer
manifest (47).
CYP2A6 is the principle enzyme metabolizing nicotine to its metabolite cotinine.
Tryptamine is specific and relatively selective inhibitor for CYP2A6 and it is
suggested that is may be useful in vivo to decrease smoking by inhibiting nicotine
metabolism (48).
Critical assessment
Chemical
Tryptamine can be oxidized and thereby radicals are formed. Tryptamine can react
with aldehydes and ketones. It forms adducts with other cigarette components and
forms also carbolines via Pictet-Spengler condensation.
In vivo
Tryptamine derivatives, such as carbolines, which are readily formed in cigarette
smoke, affect the monoamine oxidase system. Tryptamine inhibits the CYP2A6
enzyme and could be therefore inhibit the nicotine degradation. No data were