The Contribution of cocoa additive to cigarette smoking addiction

Page 50 of 207 RIVM report 650270002
Serotonin
.
SMOKING COCOA INTAKE BY EATING BANANA
25 cig. 3 chocolate cocoa
(1 % cocoa) bars of 60 g powder (25 g) (100 g) .
Serotonin (µg) 15 35 (milk) (4) 18.75 (4) 5000 – 15000
174 (dark) (4)
.
Little is known about the profile of the pyrolysis/combustion products of serotonin.
(3, 11)
Conclusion
The daily intake of serotonin from cocoa added to cigarettes is marginal compared
with that of serotonin intake from other sources, like chocolate or fruit (banana).
Assuming similar bioavaibility, the plasma concentration reached after ingestion of
serotonin from chocolate sources or plants is expected to be significantly higher, than
after exposure from cigarettes. Since, serotonin is an endogenous compound, it is not
expected that the inhaled amount will significantly affect the plasma concentration.
However, the different route of application via smoking as compared to other sources
should be taken into account. Therefore, local effect of serotonin on the respiratory
system might be a point of concern.
PHARMACODYNAMICS
Mechanism of action
Over the past ten years, evidence obtained from molecular, biochemical and
physiological studies has revealed the existence of fifteen serotonin receptor
subtypes, which can be subdivided into seven major families (5-HT1-7 subtypes) (12).
Serotonin both stimulates and inhibits nerves and smooth muscles in the
cardiovascular, respiratory and gastrointestinal systems. Platelet membrane contains
serotonin receptors (5-HT2) that enhance aggregation when stimulated (6).
Serotoninergic neurons are found in the brain stem where they are concentrated in the
raphe nuclei. Projections from serotonin neurons reach the cortical forebrain,
olfactory bulb, septum, hippocampus, thalamus, hypothalamus, basal ganglia
(caudate, putamen and globus pallidus), substantia nigra, cerebellum, and spinal cord.
Serotonin produces numerous pharmacological effects mainly because of the
diversity of its receptors that are either ionotropic (ligand-gated ion channel
receptors) or metabotropic (G-protein-coupled receptors). Serotonin is an autacoid
that acts both at microdistances as neurotransmitters and at long distances as a
hormone. The majority of serotonin receptors are metabotropic G protein-linked. The
exception is the 5HT3 receptor, which is ionotropic. This ligand-gated monovalent
cation channel is present in high density in the brain region that contains the emetic
centre and its antagonists (e.g., ondansetron) are potent anti-emetics. The
metabotropic serotonin receptors are important targets in the brain for action of
numerous therapeutics including antidepressants, anxiolytic, and antimigraine drugs.
By analogy with neural antiacetylcholine receptors these drugs are likely to act as
channel blockers. The metabotropic serotonin receptors are linked to either Gpprotein
and their activation decreases cAMP synthesis (5-HT1A-F) or to Gs protein,
that activates phospholipase C and increases synthesis of IP3 and diacylglycerol (5-
HT2A-C). Although there are many high-affinity agonists and antagonists for all
subtypes, there are none that are totally selective for one subtype (13).