MDMA-LIKE STIMULUS EFFECTS OF ALPHA-ETHYLTRYPTAMINE AND THE ALPHA-ETHYL HOMOLOG OF DOM

One-carbon homologation of phenylalkylamine or indolylalkylamine hallu cinogens containing an alpha-methyl substituent typically results in a reduction of hallucinogenic potency; however, this same structural ch ange 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 e mployed to determine if the alpha-ethyl homologs of the hallucinogens 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) and alpha-methyl tryptamine (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 pub lished) and alpha-MeT (this study), MDMA stimulus generalization occur red both to alpha-EH DOM (ED(50) = 1.3 mg/kg) and alpha-EtT (ED(50) = 3.5 mg/kg). A (+)amphetamine stimulus (training dose = 1.0 mg/kg) only partially generalized to these two agents, suggesting that the MDMA s timulus generalization involves more than a simple amphetamine-like ac tion. As such, this is the first demonstration that classical hallucin ogens can produce MDMA-like effects upon homologation and that MDMA-li ke stimulus effects can be associated with an indolylalkylamine. Furth ermore, these results continue to support the concept that an intact m ethylenedioxy ring system, such as that found in MDMA and other MDMA-r elated agents, is not a structural requirement for drugs to produce MD MA-like effects.