Abstract
4-Methylaminorex is a stimulant drug of abuse that exists as four stereoisomers: cis-4R,5S,cis-4S,5R,trans-4S,5S, andtrans-4R,5R. These isomers have previously been shown to differ markedly in various respects. In the present study we assessed the effects of the isomers of 4-methylaminorex (2.5, 5.0, and 10 mg/kg i.p.) on extracellular dopamine and 5-hydroxytryptamine (5-HT) levels in the nucleus accumbens, as well as behavior in the rats simultaneously. The relative concentrations of the isomers in the brain were also measured. The samples were collected by in vivo microdialysis and then analyzed for neurotransmitters with high-performance liquid chromatography/electrochemical detection and forcis- and trans-4-methylaminorex with gas chromatography/mass spectrometry. The behavioral effects of the isomers were assessed from videotapes recorded during the microdialysis experiments. All isomers elevated the extracellular levels of both dopamine and 5-HT, with the exception oftrans-4R,5R. The rank order of potency for elevating dopamine wastrans-4S,5S >cis-4S,5R ≈cis-4R,5S >trans-4R,5R, and for elevating 5-HTcis-4S,5R >trans-4S,5S ≈cis-4R,5S >trans-4R,5R. Analysis of the behavioral data, together with the neurochemical data, suggests that behavioral effects of the isomers of 4-methylaminorex are related to drug-induced dopamine release and, in the case of higher doses of the most efficacious isomers, to 5-HT as well. The brain concentrations of the isomers did not reflect their neurochemical efficacy, which implies that their differences are pharmacodynamic rather than pharmacokinetic.
Footnotes
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This work was supported by the Yrjö Jahnsson Foundation, Helsinki, Finland. Portions of this research were presented at the 38th Meeting of the International Association of Forensic Toxicologists, August 2000, Helsinki, Finland [Ellermaa S, Kankaanpää A, Meririnne E and Seppälä T (2000) The neurochemical effects of cis-4-methylaminorex (‘Euphoria’): a microdialysis study in the rat, in Program and Abstracts (Rasanen I ed) p 177, Oikeuslääketieteellinen laitos, Helsinki, Finland], and the 30th Annual Meeting of the Society for Neuroscience, November 2000, New Orleans, LA [Kankaanpaa AL, Meririnne EJ, Ellermaa S and Seppälä T (2000) Comparison of acute neurochemical effects and brain concentrations of the stereoisomers of 4-methylaminorex. Soc Neurosci Abstr26:388].
- Abbreviations:
- 5-HT
- 5-hydroxytryptamine
- DOPAC
- 3,4-dihydroxyphenylacetic acid
- HVA
- homovanillic acid
- 5-HIAA
- 5-hydroxyindoleacetic acid
- AUC
- area under the curve
- MDMA
- 3,4-methylenedioxymethamphetamine
- NMDA
- N-methyl-d-aspartate
- Received August 7, 2001.
- Accepted October 25, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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