title: Effect of 3,4-methylenedioxymethamphetamine on the toxicokinetics and sedative effects of the drug of abuse, γ-hydroxybutyric acid.
abstract: γ-Hydroxybutyric acid (GHB) is widely abused in combination with other club drugs such as 3,4-methylenedioxymethamphetamine (MDMA). The objectives of this study were to characterize the effects of MDMA on GHB toxicokinetics/toxicodynamics (TK/TD) and evaluate the use of monocarboxylate transporter (MCT) inhibition as a potential treatment strategy for GHB overdose when GHB is abused with MDMA. Rats were administered GHB 400 mg/kg i.v. alone or with MDMA (5 mg/kg i.v). Effects of MDMA and of the MCT inhibitor, l-lactate, on GHB TK and sedative effects were evaluated. The results of this study demonstrated no significant effect of MDMA on GHB TK or TD. GHB plasma concentrations were unchanged, and GHB concentration-effect relationships, based on plasma and brain concentrations and the return-to-righting reflex (RRR), were similar in the presence and absence of MDMA. l-Lactate administration resulted in a significant decrease in the sedative effect (RRR) of GHB when it was coadministered with MDMA. Our results indicate that MDMA does not affect the TK/TD of GHB at the doses used in this study, and MCT inhibition using l-lactate, an effective overdose treatment strategy for GHB alone, is also effective for GHB overdose when GHB is coingested with MDMA.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, New York, 14214-8033.
authors.forename: Nisha
authors.initials: N
authors.lastname: Vijay
authors.forename: Marilyn E
authors.initials: ME
authors.lastname: Morris
mesh_terms: D000818:Animals; D006885:Hydroxybutyrates / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity*; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics* / Q000633:toxicity*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006885:Hydroxybutyrates; D006993:Hypnotics and Sedatives; C111420:4-hydroxybutyric acid; D018817:N-Methyl-3,4-methylenedioxyamphetamine
keywords: GHB; MDMA; blood-brain barrier; drug interaction; l-lactate; membrane transport/transporters; monocarboxylate transporters; overdose treatment; toxicokinetics; γ-hydroxybutyrate