The Contribution of cocoa additive to cigarette smoking addiction

RIVM report 650270002 Page 59 of 207
Serotonin
results in “serotonin syndrome”. The serotonin syndrome has increasingly been
recognised in patients who have received combined serotonergic drugs. This
syndrome is characterised by a constellation of symptoms (confusion, fever,
shivering, diaphoresis, ataxia, hyperelflexia, myoclonus or diarrhoea) in the setting of
the recent addition of a serotonergic agent. The most common drug combinations
causing the serotonin syndrome are monoamine oxidase inhibitors (MAOIs) and
serotonin selective reuptake inhibitors (SSRIs), MAOIs and tricyclic antidepressants,
MAOIs and tryptophan. This syndrome is caused by excess serotonin availability in
the CNS at the 5-HT1A-receptor (48). Propranolol increased the level of serotonin in
the incubation medium of cultured Leydig cells. This serotonergic action of the drug
could contribute to the impairment of sexual function reported during propranolol
treatment in man (49). Epidemiological studies proved that newer anorexigen,
fenfluramine (or its stereoisomer, dexfenfluramine) considerably increases the risk of
pulmonary hypertension through inhibition of the serotonin receptor. The
development of pulmonary hypertension is probably due to the increased plasma
serotonin concentration (50).
Furthermore, serotonin can affect the toxicity of drugs. Rats are more sensitive to the
nephrotoxicity of the antituberculosis drug capreomycin, than mice, rabbits, hamsters,
cats, or guinea pigs. This difference in sensitivity may be related to species
differences in serotonin concentrations in mast cells. Rats have a relatively high
concentration of serotonin in their mast cells. Capreomycin degranulates mast cells
leading to the release of serotonin which is nephrotoxic (13).
Critical assessment
Chemical
Serotonin can be oxidized and thereby radicals are formed.
In vivo
Several compounds affect the metabolic pathway of serotonin. Several agents interact
with the large serotonin receptor family and affect thereby the local or systemic
serotonin level and cause typical serotonin clinical effects. No data were available on
respiratory interaction effects via inhalation.
Conclusion
Chemical
Serotonin can form radicals by oxidation.
In vivo
Serotonin showed several systemic interaction effects in the body. The contribution
of serotonin in cigarette to the systemic interaction effects can not be established and
need to be studied.
DEPENDENCY
The involvement of serotonin in the nicotine dependence was shown in the following
study. Chronic nicotine administration (nicotine in water during 50 days) to male
NMRI mice altered the serotonin metaboles in the brain. This alteration found in the
brain indicated that serotonin might be involved in nicotine dependence and
withdrawal (30).
Various studies have shown a link between tobacco dependency and serotonin in