The Contribution of cocoa additive to cigarette smoking addiction

RIVM report 650270002 Page 145 of 207
Phenylethylamine
exposure from cigarettes. Also, the different route of application via smoking as
compared with other sources should be taken into account. Therefore, the systemic
and the local effect of smoking related exposure to phenylethylamine might be a
point of concern. Since nothing is known about the pyrolysis/combustion products of
phenylethylamine, this may also be a point of concern.
PHARMACODYNAMICS
Mechanism of action
Phenylethylamine is classified as a neuromodulator of dopaminergic and possibly
serotonergic and noradrenergic synapses. At the molecular physiological level,
phenylethylamine potentiates transmission by postsynaptic and possibly presynaptic
action. As yet, no conclusive evidence for phenylethylamine receptor has been shown
(11). However, there is growing body of evidence for the existence that trace amines
(TA) such as phenylethylamine, tyramine and tryptamine, function independently of
the classical amine transmitters and mediate some of their effects via specific
receptors. A study with 3 H-phenylethylamine in rat brain suggested the possibility of
a specific binding site for phenylethylamine. Recently, a family of related mammalian
15 G protein-coupled receptors was identified of which two members (TA1- and TA2receptors)
have been shown to specifically bind and/or be activated by trace amines,
such as phenylethylamine (12).
Pulmonary system
breathing frequency: no data available.
tidal volume: no data available.
lung compliance: no data available.
airway resistance: Phenylethylamine caused an initial relaxation (at 10 -7 - 10 -5
M) of the guinea-pig isolated lung parenchymal strip followed by contraction at
higher concentration (10 -4 – 10 -3 M). Phenylethylamine produced a
bronchoconstriction of perfused lungs, with a mean effective concentration
(EC50) (n =5) of 4.53x10 -4 M. The relaxation of phenylethylamine seems to be
mediated by ß-adrenoreceptors. The contraction effect of phenylethylamine does
not seem to be mediated by α-adrenergic, muscarinic, histaminergic, serotonergic
or dopaminergic receptor stimulation. It is not clear which receptors are involved
phenylethylamine contraction effects (13).
Cardiovascular system
blood pressure: Phenylethylamine increased mean aortic blood pressure, total
peripheral vascular resistance, left ventricular dP/dt, and (dP/dt)/P in chloraloseanesthetized
dogs. Pretreatment with phentolamine reduced the increases in aortic
blood pressure and total peripheral vascular resistance produced by
phenylethylamine, whereas the effects of phenylethylamine on left ventricular
dP/dt and (dP/dt)/P were abolished by propranolol, but increased after
phentolamine pretreatment. Furthermore, both the cardiac and vascular effects of
phenylethylamine were abolished by desipramine. These results indicate that
phenylethylamine exerts both positive inotropic and vasoconstrictory effects,
probably by releasing endogenous norepinephrine from the adrenergic nerve
endings. (The phenylethylamine dose was not mentioned in the abstract of the
article) (14).