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Artigo em Inglês | MEDLINE | ID: mdl-28219712

RESUMO

Methylenedioxypyrovalerone (MDPV) is a new psychostimulant cathinone acting as a selective dopamine transporter blocker. Due to the concomitant consumption of ethanol (EtOH) and new psychoactive substances, it is of interest to explore a possible pharmacological interaction between MDPV and EtOH. In locomotor activity assays, EtOH (1g/kg i.p.) elicited a reduction in the stimulant effect induced by low doses of MDPV (0.1-0.3mg/kg, s.c.) in rats, jointly with a decrease in blood and brain MDPV concentrations. Experiments in rat liver microsomes showed different effects depending on the [MDPV]/[EtOH] relationship, evidencing, at certain concentrations, the enhancing effect of EtOH on MDPV metabolism. These suggest that EtOH interacts with MDPV at microsomal level, increasing its metabolic rate. The interaction between both substances was also supported by results in plasma EtOH concentration, which were significantly increased by MDPV, in such a manner that EtOH elimination rate was significantly reduced. The possible toxicological impact of this phenomenon deserves further investigation. In contrast, the rewarding properties of MDPV were unaltered by EtOH. Microdialysis experiments verified that, in the NAcc, both substances could also act synergistically, in such a manner that extracellular dopamine concentrations are maintained. Finally, if the psychostimulant effect induced by MDPV decreased with EtOH, it could favor the boosting and re-dosing in search of the desired effects. However, as the rewarding effect of each dose of the substance would not decrease, the addictive liability could increase considerably. Moreover, we must warn about the increase in EtOH concentrations when consumed concomitantly with MDPV.


Assuntos
Alcaloides/metabolismo , Comportamento Animal/efeitos dos fármacos , Benzodioxóis/metabolismo , Benzodioxóis/farmacologia , Estimulantes do Sistema Nervoso Central/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , Condicionamento Clássico/efeitos dos fármacos , Interações Medicamentosas , Etanol/metabolismo , Etanol/farmacologia , Pirrolidinas/metabolismo , Pirrolidinas/farmacologia , Animais , Benzodioxóis/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Etanol/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Microdiálise , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Pirrolidinas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Catinona Sintética
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