The Contribution of cocoa additive to cigarette smoking addiction

More documents

Recommendations

Info

Page 152 of 207 RIVM report 650270002 Phenylethylamine Mutagenicity Human No data available. Animal No data available. Other Critical assessment Phenylethylamine (5 mg) produced symptoms like headache, dizziness and discomfort in some volunteers (n = 27). The LD50 value in rats varies between 100 mg/kg (i.p.) to 800 mg/kg (oral). No data are available on the inhalation toxicological effect of phenylethylamine. Therefore, no conclusion can be drawn whether the phenylethylamine dose in one cigarette (0.49 mg/cigarette) will have significant systemic and local toxicological effects. Conclusion No data are available on inhalation toxicological effects of phenylethylamine. The long-term effect of this compound via the respiratory system needs to be studied. INTERACTIONS Chemical A reaction of phenylethylamine and other biogenic amines such as serotonin, dopamine, histamine, tyramine and tryptamine with components of cigarette smoke was observed. Both formaldehyde and cyanide, which are known to be present in cigarette smoke, were involved in the reaction with the primary amines. The reaction was time dependent and was enhanced by an increase in temperature or by incubation under alkaline conditions. Cyanomethyl adduct formation was increased when smoke from cigarettes with higher tar and nicotine content was used. When the amines were incubated with human saliva obtained after cigarette smoking, cyanomethylamine products were readily detected (35). When the amine substrates phenylethylamine, ptyramine and serotonin were incubated with the cigarette smoke solution, lipophilic adducts were formed non-enzymatically. These mixtures exhibit considerable MAO inhibitory activity. The inhibition of MAO by cigarette smoke may well be related to the low platelet MAO activity found in cigarette smokers (36). In vivo The safety, pharmacokinetics, and pharmacodynamics of single oral doses up to 48 mg and daily (for 28 days) doses up to 24 mg mofegiline were investigated in healthy male volunteers. Mofegiline rapidly and markedly inhibited platelet monoamine oxidase B (MAOB) activity, which returned to baseline within 14 days. Urinary excretion of phenylethylamine increased proportionately with doses up to 24 mg (37). 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
RIVM report 650270002 Page 153 of 207 Phenylethylamine 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 (0.25 mg/kg/min) were unaffected by the prior administration of either phenoxybenzamine (1.5 mg/kg, iv) or pimozide (0.5 mg/kg, 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. In the present experiments, the administration of the monoamine oxidase type B inhibitor, deprenyl (1 mg/kg, iv), did not effect significant changes in cerebral blood flow or cerebral oxygen consumption. However, following deprenyl, the administration of phenylethylamine (5 µg/kg/min), a concentration which was without effect in normal animals, significantly reduced cerebral blood flow (19). Monoamine oxidase (MAO) is responsible for the pulmonary metabolism of phenylethylamine. The effects of treatment of rats with the tricyclic antidepressant desmethylimipramine (DMI) on the disposition phenylethylamine in isolated perfused rat lungs was investigated. During a 10-min perfusion at a concentration of 10 -6 M phenylethylamine were rapidly taken up and extensively metabolized by lungs from control animals. Phenylethylamine clearance in perfused lung was decreased in a dose-related manner by DMI treatment with a corresponding decrease in its metabolism. In efflux experiments, unmetabolized phenylethylamine was only found in the perfusate from lungs of DMI-treated rats. It was concluded that phenylethylamine clearance after DMI results almost entirely from inhibition of pulmonary MAO. The data also suggest that there may be two discrete pools of MAO in lung, one of which is relatively unaffected by DMI (21). Critical assessment Chemical Phenylethylamine can react with aldehydes and cyanides. Adducts formed with other cigarette components have MAO inhibitory properties. In vivo Phenylethylamine shows an interaction with monoamine oxidase inhibitors (MAOI). The MAO-I increases the phenylethylamine level in the body. It is plausible that phenylethylamine availability from cigarette smoking will be increased when MAO is inhibited. Conclusion Chemical Phenylethylamine can react with aldehydes and cyanides in cigarettes and the formed adducts can inhibit MAO. In vivo MAO is responsible for the metabolism of phenylethylamine. Therefore, MAO-I increases phenylethylamine level in the body. DEPENDENCY Phenylethylamine is an endogenous brain amine, which has been characterised as an endogenous amphetamine. The rewarding properties of the structurally similar drug amphetamine in humans and other species indicate a possible role for endogenous
Page 1 and 2:
RIVM report 650270002/2002 The cont
Page 3 and 4:
RIVM report 650270002 Page 3 of 207
Page 5 and 6:
Page 7 and 8:
Page 9 and 10:
Page 11 and 12:
Page 13 and 14:
Page 15 and 16:
Page 17 and 18:
Page 19 and 20:
Page 21 and 22:
Page 23 and 24:
Page 25 and 26:
Page 27 and 28:
Page 29 and 30:
Page 31 and 32:
Page 33 and 34:
Page 35 and 36:
Page 37 and 38:
Page 39 and 40:
Page 41 and 42:
Page 43 and 44:
Page 45 and 46:
Page 47 and 48:
Page 47 of 207 RIVM report 65027000
Page 49 and 50:
Page 51 and 52:
Page 53 and 54:
Page 55 and 56:
Page 57 and 58:
Page 59 and 60:
Page 61 and 62:
Page 63 and 64:
Page 65 and 66:
Page 67 and 68:
Page 69 and 70:
Page 71 and 72:
Page 73 and 74:
Page 75 and 76:
Page 77 and 78:
Page 79 and 80:
Page 81 and 82:
Page 83 and 84:
Page 85 and 86:
Page 87 and 88:
Page 89 and 90:
Page 91 and 92:
Page 93 and 94:
Page 95 and 96:
Page 97 and 98:
Page 99 and 100:
Page 101 and 102: RIVM report 650270002 Page 101 of 2
Page 125 and 126: Page 125 of 207 RIVM report 6502700
Page 151: RIVM report 650270002 Page 151 of 2
Page 203 and 204:
Page 205 and 206:
Page 207:
show all

The Contribution of cocoa additive to cigarette smoking addiction

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?