Studies of dioxole ring substituted 3,4-methylenedioxyamphetamine (MDA) analogues.
D E Nichols, Robert Oberlender, K Burris, Andrew J. Hoffman, M P Johnson
Pharmacology, biochemistry, and behavior November 1989 DOI: 10.1016/0091-3057(89)90560-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical pharmacology study Peer reviewed |
|---|---|
| Population | Rats (brain tissue slices and drug discrimination assays) |
| Interventions | MDA EDA IDA fluoxetine |
| Dose | d-LSD tartrate 0.08 mg/kg or MDMA.HCl 1.75 mg/kg as training stimuli; fluoxetine 3.2 microM |
| Measures | [3H]-serotonin overflow, [3H]-dopamine overflow, R-[125I]-DOI displacement, two-lever drug discrimination assay |
| Key points | MDA and its analogue EDA were nearly equipotent in releasing serotonin and dopamine from rat brain slices, whereas IDA was considerably less potent. All three drugs fully substituted in rats trained to discriminate LSD or MDMA, but MDA was about twice as potent as EDA and five times as potent as IDA in MDMA-trained rats, and about three and seven times more potent, respectively, in LSD-trained rats. |
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.