The Contribution of cocoa additive to cigarette smoking addiction

RIVM report 650270002 Page 97 of 207
Tryptophan
glutamate agonist. The majority of tryptophan is eventually converted to carbon
dioxide but a small amount can act as a precursor of the coenzymes NAD and NADP
(10).
Of the fraction of tryptophan that enters the brain, part is metabolised to tryptamine
and possibly to kynurenine in addition to serotonin. It has been estimated that only 1
% of ingested tryptophan is metabolised to serotonin. Biosynthesis of serotonin
requires two enzymatic steps: L-tryptophan is first hydroxylated by tryptophan
hydroxylase to L-5-hydroxytryptophan (L-5HTP) and L-5HTP is then decarboxylated
into serotonin by decarboxylase. Tryptophan hydroxylase is restricted to serotonin
neurons and therefore oral administration of tryptophan gives rise to selective
increases in serotonin synthesis and release. A range of 6-8 g/day, given in divided
doses, seems sufficient to keep tryptophan hydroxylase reasonably close to saturation
throughout most of the day. Higher doses would only increase synthesis of tryptamine
and induce tryptophan dioxygenase enzyme (25).
Excretion
No data available
Kinetic parameters
The half-life of plasma tryptophan in healthy individuals is 2.0 ± 0.1 h (26). After
oral administration of L-tryptophan, 100 mg per kg body weight, the peak
concentration of tryptophan in plasma occurred after 1 to 2 h. Tryptophan
disappeared linearly from 2 to 5 h and exponentially from 5 to 8 h after
administration (27).
Critical assessment
The oral data indicate a high bioavailabilty, extensive distribution and metabolism of
tryptophan. There are no data on pharmacokinetics in animals and humans from
respiratory studies on tryptophan. Tryptophan is bound extensively to albumin in
plasma. Tryptophan is extensively metabolised resulting in several biologically active
compounds.
Conclusion
There are no data available on kinetics after respiratory exposure. Conclusions on
potential differences in pharmacokinetics between respiratory and oral administration
can neither be drawn based on the pharmacological and toxicological data.
TOXICOLOGY
Acute toxicity
Human
Tryptophan alone seems to produce no more side effects than placebo when given at
a moderate dose (3 g per day orally). (10).
Nausea, headache, lightheadedness and drowsiness have been reported as side effects
of tryptophan (21).
Single intake of high doses of tryptophan (> 2 g) with monoamine oxidase inhibitors
may lead to development of neurological complications. These symptoms are related
to serotonin syndrome (25).