The Contribution of cocoa additive to cigarette smoking addiction

Page 130 of 207 RIVM report 650270002
Tyramine
which are rapidly metabolized in vivo, was ineffective up to 40 mg/kg to
antagonize the effect of tetrabenazine in the shutlle box (24).
The effect of tyramine on brain noradrenaline (NA) containing neurons in the
locus coeruleus (LC) was analyzed using single unit recording techniques. In
control rats, administration of high doses of tyramine caused a slight inhibition of
firing. However, after pretreatment with the monoamineoxidase (MAO)-A
inhibitors clorgyline (10 mg/kg, i.p., 1 h) or amiflamine (3 mg/kg, i.p., 1 h)
administration of low doses of tyramine caused a consistent and dose-dependent
inhibition of firing of the noradrenergic neurons. This inhibition was reversed by
the α2-receptor antagonist yohimbine and prevented by depletion of endogenous
stores of noradrenaline (pretreatment with reserpine (10 mg/kg, i.p., 5 h) ad αmethyl-p-tyrosine
(250 mg/kg, i.p., 30 min). Pretreatment with the MAO-B
inhibitor (-)-deprenyl (10 mg/kg, i.p., 1 h) did not promote tyramine to inhibit LC
units and therefore it is suggested that this is related to a re-uptake blocking effect
of its metabolite, I-amphetamine. Apparently, tyramine, although known to be a
rather polar agent, can inhibit central noradrenergic firing rate via an indirect, α2receptor
mediated effect. The present results indicate that the serious “cheese
effect” of MAO-inhibitors may also have a central origin. Small amounts of
pressor amines, which are normally considered to be harmless, in foods
(especially cheese) can lead to a hypertensive crisis in patients on MAO-inhibitor
drug regimens, which is often termed the ‘cheese reaction’ (25).
autonomic system: Administration of tyramine (i.v. 300 µg/kg) to human
volunteers, increased plasma noradrenaline level by 145 ± 39 pg/ml (n = 6) from
the baseline. Tyramine did not affect plasma adrenaline (14). In another study,
tyramine (i.v. 15.0 micrograms/kg/min for 30 min) increased plasma
noradrenaline from 547 ± 184 to 836 ± 96 pg/ml in normal human volunteers;
plasma adrenaline was unchanged (17).
Other
Tyramine hydrochloride eyedrops (75 mM; 2 x 10 µl) evoked a significant mydriasis
both in light and dark in healthy male subjects (aged 18 – 22 years, n = 8), which was
more prominent in the light condition (change in resting pupil size; mm ± s.e.m: light
1.05 ± 0.28; dark: 0.73 ± 0.15) (26).
Critical assessment
Tyramine is an indirect acting sympathomimetic substance. It increases the release of
noradrenaline from the neural endings. The main pharmacological effect of tyramine
is the increase of the blood pressure. About 21 mg tyramine (i.v. 20 µg/kg/min in 15
min) increased the systolic blood pressure significantly. It is unlikely that tyramine
dose in cigarettes (estimated 0.4 mg/cigarette) will exert a significant increase in
systolic blood pressure.Based on the mechanism of action of tyramine by releasing
noradrenaline from the neural endings, it is expected that the dose of tyramine in
cigarettes will not have a significant effect on the bronchial function.
Conclusion
It seems unlikely that the tyramine dose in one cigarette (estimated 0.4 mg/cigarette)
could increase the systolic blood pressure significantly. The (longterm) effects of
tyramine or its pyrolysis/combustion products on the pulmonary system are unknown
and need further study.