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TITL: Effect of alpha-methyltryptamine on spontaneous activity in mice. ABST: A standard dose of 10 mg/kg (48 mu mole/kg) of (+/-)-alpha-methyltryptamine (AMT) induced a significant and long lasting increase in spontaneous activity in mice. Pretreatment of mice with either pimozide or alpha-methyl-para-tyrosine methyl ester HCl (AMPT) prevented the activity increase induced by AMT. In similar trials, methysergide or para-chlorophenylalanine (PCPA) were also found to antagonize the development of hyperactivity following a standard dose of AMT. The results suggest that both endogenous dopamine and serotonin many participate in the hyperactivity induced by AMT.
TITL: MDMA-like stimulus effects of alpha-ethyltryptamine and the
alpha-ethyl homolog of DOM. ABST: One-carbon homologation of phenylalkylamine or indolylalkylamine hallucinogens containing an alpha-methyl substituent typically results in a reduction of hallucinogenic potency; however, this same structural change has little to no effect on agents that produce MDMA-like effects. In the present investigation, rats trained to discriminate 1.5 mg/kg of MDMA (3,4-methylenedioxymethamphetamine) from saline vehicle were employed to determine if the alpha-ethyl homologs of the hallucinogens 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) and alpha-methyltryptamine (alpha-MeT) -- that is, alpha-EH DOM (BL-3912) and alpha-EtT, respectively -- would produce stimulus effects similar to those of MDMA. Although the MDMA stimulus failed to generalize to DOM (previously published) and alpha-MeT (this study), MDMA stimulus generalization occurred both to alpha-EH DOM (ED50 = 1.3 mg/kg) and alpha-EtT (ED50 = 3.5 mg/kg). A (+)amphetamine stimulus (training dose = 1.0 mg/kg) only partially generalized to these two agents, suggesting that the MDMA stimulus generalization involves more than a simple amphetamine-like action. As such, this is the first demonstration that classical hallucinogens can produce MDMA-like effects upon homologation and that MDMA-like stimulus effects can be associated with an indolylalkylamine. Furthermore, these results continue to support the concept that an intact methylenedioxy ring system, such as that found in MDMA and other MDMA-related agents, is not a structural requirement for drugs to produce MDMA-like effects.
TITL: Studies of monoamine oxidase and semicarbazide-sensitive amine
oxidase. II. Inhibition by alpha-methylated substrate-analogue monoamines,
alpha-methyltryptamine, alpha-methylbenzylamine and two enantiomers of
alpha-methylbenzylamine. ABST: The alpha-methylated substrate-analogue monoamines, dl-alpha-methyltryptamine, dl-alpha-methylbenzylamine and two optical isomers of alpha-methylbenzylamine, were shown to be inhibitors of rat lung semicarbazide-sensitive amine oxidase (SSAO), with dl-alpha-methyltryptamine being the most potent and d-alpha-methylbenzylamine, the least. The three compounds, dl-alpha-methyltryptamine and the two isomers of alpha-methylbenzylamine also inhibited rat brain monoamine oxidase (MAO)-A and -B with a greater selectivity towards MAO-A. Preincubation of rat lung and brain homogenates with either of these compounds revealed that the inhibition of MAO and SSAO is reversible. The modes of inhibition of MAO-A and -B were competitive with the substrates tested. However, inhibition of SSAO by dl-alpha-methyltryptamine was found to be a mixed type (with a Ki value of 47 microM) and those by the racemic form and two isomers of alpha-methylbenzylamine were non-competitive (with Ki values of 90 microM for the racemic compound, 1070 microM for the d-isomer and 72 microM for the l-isomer). The present results indicate that SSAO can recognize optical isomers and that some alpha-methylated monoamines tested in the present study inhibit SSAO with properties different from those as MAO inhibitors.
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