Stimulus effects of N-monoethyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDE) and N-hydroxy-1-(3,4-methylenedioxyphenyl)-2-aminopropane (N-OH MDA) in rats trained to discriminate MDMA from saline.
Tests of stimulus generalization were conducted using rats trained to discriminate 1.5 mg/kg of N-monomethyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane HCl (MDMA) from saline in order to determine if two structurally related analogs (MDE and N-OH MDA) would produce similar stimulus effects. The MDMA-stimulus (MDMA, ED50 value = 0.76 mg/kg) generalized both to MDE (ED50 value = 0.73 mg/kg) and N-OH MDA (ED50 value = 0.47 mg/kg). Administration of (+)amphetamine resulted in partial generalization (maximum of 49% MDMA-appropriate responding) in the MDMA-trained animals. Taken together with our previous studies showing that MDMA substitutes for the phenylisopropylamine stimulant (+)amphetamine, but that neither MDE nor N-OH MDA substitute for (+)amphetamine or for the phenylisopropylamine hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), the present results [i.e., MDMA-stimulus generalization to MDE, N-OH MDA, but not to (+)amphetamine] suggest that 1) MDMA produces effects other than those that may be considered amphetamine-like, and 2) MDE and N-OH MDA are MDMA-like agents with even less of an amphetamine-like component of action than MDMA itself.
Glennon
R A
RA
Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia, Virginia Commonwealth University, Richmond 23289-0581.
Misenheimer
B R
BR
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000661:Amphetamine / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D004192:Discrimination, Psychological; D004305:Dose-Response Relationship, Drug; D005795:Generalization, Stimulus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D051381:Rats; D011919:Rats, Inbred Strains
D000662:Amphetamines; D015104:3,4-Methylenedioxyamphetamine; C062690:N-hydroxy-1-(3,4-methylenedioxyphenyl)-2-aminopropane; D000661:Amphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C051800:3,4-methylenedioxyethamphetamine