The Contribution of cocoa additive to cigarette smoking addiction

More documents

Recommendations

Info

Page 118 of 207 RIVM report 650270002 Tryptamine available on respiratory interaction effects via inhalation. Conclusion Chemical Tryptamine can react with several compounds, such as aldehydes and ketones. In vivo Tryptamine derivatives seem to affect the monoamine oxidase system and the CYP2A6 enzym. The contribution of tryptamine in cigarette smoking with respect to these mechanisms can not be established from available data and need to be studied. DEPENDENCY It is suggested that tryptamine is seen as allosteric regulator of serotonin receptors. The modulatory effects of tryptamine are mediated either directly at presynaptic and/or postsynaptic tryptamine binding sites of serotonin neurons or by inducing allosteric changes at serotonin receptors (12). Several studies have shown some relationship between nicotine or tobacco dependency and serotonin activity in the brain (49-52). The tryptamine affected serotonin activity may implicate that tryptamine could play a role in the tobacco dependency process. On the other hand, the craving qualities of chocolate have been thoroughly reviewed and the conclusion seems to be that the pharmacological active compounds in cocoa do not contribute to chocolate craving (53). Effects on smoking cessation CYP2A6 is the principle enzyme metabolizing nicotine to its metabolite cotinine. Tryptamine is specific and relatively selective for CYP2A6 and it is suggested that is may be useful in vivo to decrease smoking by inhibiting nicotine metabolism (48). Critical assessment The regulation of the serotoninergic system in the brain by tryptamine and the role of this system in the tobacco dependency seems to indicate that tryptamine may has a role in the tobacco dependency process. From literature on chocolate craving, it seems that pharmacological active compounds does not contribute to chocolate craving. Conclusion Serotonin (which is regulated in the brain by tryptamine) plays a role in the nicotine dependency. It is not clear how the natural amount of tryptamine from tobacco (which is probably lower than the endogenous amount in the body) may contribute to the process of addiction. The longterm effects of tryptamine and its interaction effects with other agents in the cigarette smoke on the pulmonary system and in the tobacco addiction process are not known and need to be studied. COMMERCIAL USE Tryptamine is used as a raw material for the synthesis of the vasodilator and antihypertensive, vincamine (54). BENEFICIAL EFFECTS Tryptamine is an endogenous neuroactive metabolite of tryptophan. Tryptamine is a
RIVM report 650270002 Page 119 of 207 Tryptamine potent inhibitor of protein biosynthesis, via the competitive inhibition of tryptophanyl-tRNA synthetase (TrpRS). The results indicate that long-term tryptamine treatment of HeLa cells led to a significant increase in the half-life of TrpRS. It was shown that tryptamine is an effective inhibitor of HeLa cell growth. In contrast to the well-characterized antineoplastic compounds, resistance to tryptamine at very low levels was difficult to achieve, i.e. the 2-fold resistant subline was selected after 19 months of treatment of HeLa cells with gradually increasing concentrations of tryptamine. It was suggested that tryptamine could be a potential anti-cancer drug (55). Critical assessment Not relevant. Conclusion Not relevant. SUMMARY AND FINAL CONCLUSION The natural amount of tryptamine in tobacco leaves is at least 5000 times higher than the tryptamine amount from added cocoa to tobacco. Therefore, it is debatable whether tryptamine should be considered as an additive to tobacco. The daily intake of tryptamine from cigarettes (from tobacco leaves and from added cocoa) is is higher than the intake from other sources, like chocolate or tomato. Assuming similar bioavailability, the plasma concentration reached after ingestion of tryptamine from chocolate sources or other food sources is expected to be lower, than after exposure from cigarettes. No conclusion can be drawn about the amount of tryptamine in cigarettes compared with the amount present in mammalian body. Tryptamine is a neurotransmitter or a modulator of neurotransmission. Tryptamine produces pharmacological effects in man that are similar to LSD and other tryptamine derivatives. Such effects are tachypnea, tachycardia, behavioral changes and hallucinations. Experiments with rats showed that tryptamine evoke effects, which are related to serotonin receptors. It has a biphasic effect on the arterial tone, induction of acquisition deficit, hypothermia and anorectic effect and affected the glucose plasma level. The tryptamine dose used to show these effects were in the range of 1 µg/dose (i.c.v.) and 5 mg/kg body weight (ipr.). However, no data are available on tryptamine pharmacological effects by respiratory studies. It is not clear whether the estimated potential tryptamine dose in cigarette (1000 µg/day) exerts any respiratory effects, as only data are available via other routes. Little is known about tryptamine pharmacokinetics in man from respiratory studies on tryptamine. It seems that oral tryptamine is inactive and tryptamine level in the brain is affected by tryptophan load. Tryptamine is synthesised by amino acid decarboxylase (AAD) from tryptophan in several tissues. The major route of catabolism for tryptamine is one of enzymatic inactivation. Tryptamine is excreted in the urine after oral loading with L-tryptophan. Tryptamine produces pharmacological effects in man which are similar to those produced by LSD, mescaline, psilocin and other tryptamine derivatives. These effects include tachycardia, tachypnea, mydriasis, hyperreflexia, behavioral changes and in man, hallucinations. No toxicological data are available from tryptamine inhalation studies. Intravenous data on tryptamine in rats, indicate that 15 mg/kg dose
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: RIVM report 650270002 Page 67 of 20
Page 117: RIVM report 650270002 Page 117 of 2
Page 125 and 126: Page 125 of 207 RIVM report 6502700
Page 169 and 170:
Page 171 and 172:
Page 173 and 174:
Page 175 and 176:
Page 177 and 178:
Page 179 and 180:
Page 181 and 182:
Page 183 and 184:
Page 185 and 186:
Page 187 and 188:
Page 189 and 190:
Page 191 and 192:
Page 193 and 194:
Page 195 and 196:
Page 197 and 198:
Page 199 and 200:
Page 201 and 202:
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?