The Contribution of cocoa additive to cigarette smoking addiction

Page 166 of 207 RIVM report 650270002
Octopamine
Other
Critical assessment
Octopamine is known to exert adrenergic effects in mammals, although specific
receptors have been cloned only in invertebrates. Octopamine stimulates α2 and ß3adrenergic
receptors in rats. Furthermore, it affected the cAMP level in the cell via
the D1-receptor. No data are available on the pulmonary effects of inhaled
octopamine. Because octopamine is much less potent than noradrenaline on the α and
ß-adrenergic receptors, it is likely that a large amount of octopamine needs to be
inhaled to affect the pulmonary system. Octopamine has positive chronotropic and
inotropic effectson dog heart, but is significantly less potent than noradrenaline.
Octopamine has a central hypotensive effect, and a peripheral hypertensive or
hypotensive effect in rats depending on the α or ß-adrenergic effect. Octopamine does
affect the central catechol amine level and thus affects the CNS.
Conclusion
No data are available on inhaled octopamine effect on the pulmonary system. Based
on the in vitro data, octopamine is less potent than noradrenaline and therefore a large
amount of octopamine needs to be inhaled to affect the pulmonary system.
PHARMACOKINETICS
Absorption
The enteric absorption is complete. However, metabolic enzymes in the gut of human
are responsible for a significant ‘first pass effect’ (29).
Bioavailability
The urinary excretion of the unchanged drug and its metabolites has been compared
after intravenous and oral administration of 3 H-octopamine to eight patients. Identical
amounts of 3 H-activity (80% of the dose) were excreted after the two routes of
dosing. Significant differences were found in the fraction of free urinary octopamine,
which amounted to 10.5% of the dose after infusion and 0.58% after oral
administration (29). These differences indicate that the bioavailability through oral
exposure is significantly lower than through i.v. exposure.
Distribution
The physiologically more active m-octopamine has been found in association with poctopamine
in 10 organs of the rat. m-Octopamine is present in concentrations equal
to those of p-octopamine in heart, spleen, and liver and in concentrations from 30 to
60% of p-octopamine in adrenals, vas deferens, brain, kidney, large intestine, bladder,
and lungs. In vivo inhibition of monoamine oxidase (MAO) markedly increased the
concentrations of both m- and p-octopamine in all organs examined. Both amines
were virtually absent from all organs except the adrenals following chemical
sympathectomy with 6-hydroxydopamine, thereby establishing that m- and poctopamine
are localized within sympathic nerve endings (28).
3 H-octopamine was found to be accumulated in human platelets, achieving a
maximum concentration gradient of 30:1 (30).
The measured concentration (ng/g wet tissue) of octopamine in rat brain was as
follows: whole brain (less cerebellum) (0.6); hypothalamus (3.2); striatum (0.5) and
cortex (0.6). Administration of pargyline (MAO-B inhibitor) resulted in an increase