MDMA-like stimulus effects of alpha-ethyltryptamine and the alpha-ethyl homolog of DOM.
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.
Glennon
R A
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Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0540.
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects; D005795:Generalization, Stimulus / Q000187:drug effects; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D014363:Tryptamines / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine
D000697:Central Nervous System Stimulants; D008781:Methyltyrosines; D014363:Tryptamines; C006179:dimoxamine; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D015104:3,4-Methylenedioxyamphetamine; D019805:alpha-Methyltyrosine; D014446:Tyrosine 3-Monooxygenase; C038034:etryptamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D003913:Dextroamphetamine