title: Studies of dioxole ring substituted 3,4-methylenedioxyamphetamine (MDA) analogues.
abstract: The 3,4-ethylidenedioxy and 3,4-isopropylidenedioxy analogues, EDA and IDA, respectively, of 3, 4-methylenedioxyamphetamine (MDA) were compared to MDA in drug-stimulated [3H]-serotonin overflow from prelabelled rat hippocampal slices, [3H]-dopamine overflow from prelabelled rat caudate slices, in their ability to displace the 5-HT2 agonist R-[125I]-DOI from rat brain cortical binding sites. They were also compared in the two-lever drug discrimination assay in rats, utilizing d-LSD tartrate (0.08 mg/kg) or MDMA.HCl (1.75 mg/kg) as the training stimulus. MDA and EDA were nearly equipotent in inducing release of both [3H]-monoamine transmitters, while IDA was considerably less potent. Pretreatment of hippocampal slices with the 5-HT-uptake inhibitor fluoxetine (3.2 microM) blocked the [3H]-5-HT overflow induced by MDA. In the drug discrimination experiments, complete substitution occurred with all three drugs in both LSD- and MDMA-trained rats. The ED50 values indicated that MDA had about twice the potency of EDA, and five times the potency of IDA in MDMA-trained rats. In the LSD-trained animals, MDA was about three times more potent than EDA and about seven times more potent than IDA. The KI values for displacement of R-[125I]-DOI generally parallel the results of the LSD transfer tests.
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907.
authors.forename: D E
authors.initials: DE
authors.lastname: Nichols
authors.forename: R
authors.initials: R
authors.lastname: Oberlender
authors.forename: K
authors.initials: K
authors.lastname: Burris
authors.forename: A J
authors.initials: AJ
authors.lastname: Hoffman
authors.forename: M P
authors.initials: MP
authors.lastname: Johnson
mesh_terms: D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006213:Hallucinogens / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*
chemical_list: D000662:Amphetamines; D006213:Hallucinogens; D012701:Serotonin; D015104:3,4-Methylenedioxyamphetamine; C063032:3,4-ethylenedioxyamphetamine; C063031:3,4-isopropylidinedioxyamphetamine; D004298:Dopamine