The Contribution of cocoa additive to cigarette smoking addiction

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Page 146 of 207 RIVM report 650270002 Phenylethylamine heart rate: Single i.v. dose of phenylethylamine was administered to five dogs. The dose- and time-related effects of phenylethylamine were determined on pupil diameter, heart rate and body temperature. Phenylethylamine dilated pupils, tended to produce an initial tachycardia followed by a bradycardia and elevated body temperature. Plasma levels of phenylethylamine correlated significantly only with increases in pupil diameter. (The phenylethylamine dose was not mentioned in the abstract of the article) (15). Renal system diuresis: no data avilable. saluresis: no data available. Nervous system central nervous system: Phenylethylamine is unique among endogenous amines in that its systemic administration produces behavioral effects. Because of it is rapidly degraded by monoamineoxidase (MAO), phenylethylamine induces pharmacological effects only at high doses or following pretreatments with MAOinhibitors (MAO-I). Its amphetamine-like effects in rats include symphatomimetic effects, increase in nonspecific motoractivity, exploratory behavior, steoreotypic behavior, electrophysiological alerting, reinforcement of complex behavior and anorectic effects (16). All the above actions of phenylethylamine, however, occur at concentrations at least 100 times higher than its endogenous concentration, which is calculated to be ± 0.24 ng/ml by assuming an even distribution within tissues (11). It is suggested that endogenous phenylethylamine may contribute to the antidepressant, stimulant, or euphoriant effects of several drugs. MAO-I markedly increase the central stimulant effects of phenylethylamine administration, and it increase brain and peripheral tissue levels of endogenous phenylethylamine. Increases in phenylethylamine urinary excretion correlate positively with improvement in depression (16). The effect of phenylethylamine on the dopaminergic nigrostriatal system of rats was described in a study. The rotational behavioral response to the i.v. injection of phenylethylamine was quantified in animals with a unilateral 6hydroxydopamine lesion of the nigrostriatal dopamine system. After phenylethylamine injection all animals (16/16) induced rotations ipsilateral to the side of the brain lesion. The dose-response curve showed that at doses as low as 1.75 mg/kg ipsilateral turns increase, with a dose-related rotational response between 1.75 mg/kg and 11.66 mg/kg, no differences being found at doses between 11.66 and 29.16 mg/kg. Rotations began a few seconds after phenylethylamine injection. The highest response was found 30-60 s after the injection. The duration of the response was dose-related (4 min for the 3.5 mg/kg doses). It was concluded that at low doses, phenylethylamine stimulates the release of dopamine from the cytoplasmic pool and behaves as a dopamine receptor agonist with a very rapid and brief action (17). The effects of phenylethylamine on striatal acetylcholine release in freely moving rats using in vivo microdialysis was studied. Phenylethylamine at 12.5 mg/kg, i.p. did not affect acetylcholine release in the striatum, whereas 25 and 50 mg/kg, i.p.
RIVM report 650270002 Page 147 of 207 Phenylethylamine induced an increase in acetylcholine release in the striatum at 15-45 min. The extracellular acetylcholine level in the striatum was significantly decreased by local application of phenylethylamine (10 and 100 µM) in the striatum via a microdialysis probe. It was concluded that systemic administration of phenylethylamine increases acetylcholine release, whereas locally applied phenylethylamine decreases striatal acetylcholine release in freely moving rats. The dopaminergic system, through the dopamine D-2 receptor, seems to be involved in the locally applied phenylethylamine-induced decrease in acetylcholine in the striatum (18). The cerebrovascular actions of phenylethylamine, an amine that has been implicated in the pathogenesis of migraine, were investigated in 16 anesthetized baboons. The influence of monoaminergic blocking agents and of a specific inhibitor of monoamine oxidase upon the cerebral circulatory and metabolic actions of phenylethylamine were examined. The reductions in cerebral blood flow (28 percent) and cerebral oxygen consumption (31 percent) that accompany the intracarotid administration of phenylethylamine (24.2 µg/kg body weight/min) were unaffected by the prior administration of either phenoxybenzamine (1.5 mg/kg bodyweight,iv) or pimozide (0.5 mg/kg body weight, iv). The administration of phenoxybenzamine and pimozide per se did not significantly disturb cerebral blood flow or oxygen consumption. The ability of migraine patients to oxidatively deaminate phenylethylamine is reduced at the time of their attacks. The administration of the monoamine oxidase type B inhibitor, deprenyl (1 mg/kg body weight, iv), did not effect significant changes in cerebral blood flow or cerebral oxygen consumption. However, following deprenyl, the administration of phenylethylamine (4.8 µg/kg body weight/min), a concentration which was without effect in normal animals, significantly reduced cerebral blood flow (19). The effects of phenylethylamine (6.25, 12.5, and 25.0 mg/kg body weight, i.p.) on spontaneous motor activity were examined in rats before (novel situation) and after they had experience of the test environment (familiar situation), in an undrugged state. In a novel cage, 12.5 mg/kg phenylethylamine stimulated rearing and locomotion. A dose of 25.0 mg/kg phenylethylamine also increased rearing and produced stereotyped head movements, but did not increase locomotion, in a novel environment. In a familiar cage, both 12.5 and 25.0 mg/kg phenylethylamine stimulated locomotion and sniffing, whereas rearing was unaffected by phenylethylamine treatment under these conditions. These data provide a striking instance of a qualitative change in the behavioural response to a psychostimulant compound which is associated with the relative familiarity of the animal with the test environment. In addition, the results show that phenylethylamine induces stereotypy at high doses and increases locomotor activity at moderate doses, which is a further illustration of the similarity in the unconditioned behavioural effects of phenylethylamine and amphetamine (20). autonomic system: The autonomic effects of phenylethylamine may be largely mediated by catecholamine release from sympathetic nerve endings. The central effects appear to be mediated in part by release of catecholamines and serotonin and in part by direct stimulation of specific receptors. The peripheral sympathomimetic effects of phenylethylamine is prevented by catecholamine
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