The Contribution of cocoa additive to cigarette smoking addiction

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Page 114 of 207 RIVM report 650270002 Tryptamine after a tryptophan load (28). Excretion No data are available for tryptamine excretion after tryptamine loading. Tryptamine is excreted in the urine after oral loading with L-tryptophan (30 mg/kg body weight). The urinary excretion of tryptamine increases immediately after loading and reaches a maximum in approximately 45 min (29).Tryptamine in the unconjugated form in urine collected from human volunteers was 82 ± 11 µg/g creatinine (mean ± standard error of the mean) (30). Kinetic parameters Intraventricular injection into the rat brain tryptamine resulted in rapid exponential decrease of it in the first 30 min after injection. Tryptamine showed a biphasic decrease with half-lives of 4.7 min (over the 5-10 min period) and 14.1 min (10-30 min) (31). The turnover rate is high in the rat brain (38 ng/ g brain tissue/h) (12). Critical assessment Little is known about tryptamine pharmacokinetics in man from oral and respiratory studies on tryptamine. The major route of catabolism for tryptamine is one of enzymatic inactivation. Conclusion There are no pharmacokinetic data available after tryptamine respiratory and oral loading. TOXICOLOGY Acute toxicity Human 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 details were available on the tryptamine data in that study (19). Animal Tryptamine induced serotonin (5-HT) syndrome (head weaving and hindlimb abduction) in rats through the 5-HT1A receptor. The 5-HT syndrome may also be associated with the 5-HT1A receptor in mice, as it is in rats (32). However, another study stated that the serotonin syndrome was attributed to the binding of tryptamine to 5-HT2 receptors and subsequent agonistic actions. Intravenous doses of 25 mg/kg to mice induced the 5-HT syndrome of head weaving and hind limb abduction (33). The behavioural effects of intravenously administered tryptamine were examined in mice. Tryptamine in a dose greater than 15 mg/kg induced distinct head-weaving and hindlimb abduction. These behavioural syndromes appeared immediately after the injection and disappeared within 3 min. The changes in time course of the behaviour induced by tryptamine were consistent with those of the levels of tryptamine in the brain (34). The effects of tryptamine on behavior were investigated in mice. Tryptamine at a
RIVM report 650270002 Page 115 of 207 Tryptamine dose of 50 mg/kg i.p. induced an inhibition of locomotor activity and, at doses ranging from 150 to 300 mg/kg, induced peculiar behaviors such as head twitch, head weaving, forepaw treading, hindlimb abduction and Straub tail. These behavioral effects were continuous, although tryptamine rapidly disappeared from the brain. It was concluded that tryptamine induced both the depression and excitation in the behavior of mice depending on the dosage and tryptamine -induced excitatory behaviors may be attributed to both its direct stimulation of serotonin receptors and facilitation of serotonin release (35). LD50 ipr rat: 223 mg/kg (33, 36) LD50 ipr. mouse: 100 mg/kg (33, 36) LD50 sc. mouse: 500 mg/kg (33, 36) Local tolerance Human No data available Animal No data available Repeated dose toxicity Subacute No data available Semichronic No data available Chronic No data available Carcinogenicity Human No data available Animal No data available Reproduction toxicology Human No data available Animal No data about reproduction toxicology on mammals were available. A study on drosophila reproduction showed 15% reduction of controls when adult insects mated and the young were allowed to develop on medium containing 75 mM tryptamine. Tryptamine-induced depression in reproductive success was due to decreased oviposition rate and preadult survival. Preference tests indicated that tryptamine may act as an antiattractant or antifeedant in this species (37). Mutagenicity Human No data available
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