RESUMO
This study assessed the pharmacodynamic and pharmacokinetic effects of the interaction between the selective norepinephrine (NE) transporter inhibitor reboxetine and 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in 16 healthy subjects. The study used a double-blind, placebo-controlled crossover design. Reboxetine reduced the effects of MDMA including elevations in plasma levels of NE, increases in blood pressure and heart rate, subjective drug high, stimulation, and emotional excitation. These effects were evident despite an increase in the concentrations of MDMA and its active metabolite 3,4-methylenedioxyamphetamine (MDA) in plasma. The results demonstrate that transporter-mediated NE release has a critical role in the cardiovascular and stimulant-like effects of MDMA in humans.
Assuntos
Inibidores da Captação Adrenérgica/farmacologia , Morfolinas/farmacologia , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/metabolismo , Norepinefrina/sangue , 3,4-Metilenodioxianfetamina/farmacocinética , Adulto , Pressão Sanguínea/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Interações Medicamentosas , Feminino , Alucinógenos/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Norepinefrina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/antagonistas & inibidores , Reboxetina , Adulto JovemRESUMO
BACKGROUND: MDMA (3,4-methylenedioxymethamphetamine, 'Ecstasy') produces tachycardia and hypertension and is rarely associated with cardiovascular and cerebrovascular complications. In clinical practice, beta-blockers are often withheld in patients with stimulant intoxication because they may increase hypertension and coronary artery vasospasm due to loss of beta(2)-mediated vasodilation and unopposed alpha-receptor activation. However, it is unknown whether beta-blockers affect the cardiovascular response to MDMA. METHODS: The effects of the non-selective beta-blocker pindolol (20 mg) on the cardiovascular effects of MDMA (1.6 mg/kg) were investigated in a double-blind placebo-controlled crossover study in 16 healthy subjects. RESULTS: Pindolol prevented MDMA-induced increases in heart rate. Peak values (mean+/-SD) for heart rate were 84+/-13 beats/min after MDMA vs 69+/-7 beats/min after pindolol-MDMA. In contrast, pindolol pretreatment had no effect on increases in mean arterial blood pressure (MAP) after MDMA. Peak MAP values were 115+/-11 mm Hg after MDMA vs 114+/-11 mm Hg after pindolol-MDMA. Pindolol did not change adverse effects of MDMA. CONCLUSION: The results of this study indicate that beta-blockers may prevent increases in heart rate but not hypertensive and adverse effects of MDMA.
