Vascular actions of 3,4-methylenedioxymethamphetamine in alpha(2A/D)-adrenoceptor knockout mice
Vandeputte C, Docherty JR.
Department of Physiology,
Royal College of Surgeons in Ireland,
123 St. Stephen's Green, 2, Dublin, Ireland
Eur J Pharmacol 2002 Dec 13;457(1):45-9


We have investigated the effects of 3,4-methylenedioxymethamphetamine (MDMA) on mean arterial pressure in anaesthetised wild-type and alpha(2A/D)-adrenoceptor knockout mice. In wild-type mice, MDMA (5 mg kg(-1)) produced a pressor response that declined to baseline by 2 min and fell below baseline to a depressor response by 5 min, whereas MDMA (20 mg kg(-1)) produced only a pressor response that declined to baseline by 5 min. In wild-type mice, following the injection of the selective alpha(2A/D)-adrenoceptor antagonist, 2-((4,5-dihydro-1H-imidazole-2-yl)methyl)-2,3-di-hydro-1-methyl-1H-isoindole (BRL44408), the peak pressor response to MDMA (5 or 20 mg kg(-1)) was not modified but durations of the pressor effects of both doses of MDMA were prolonged with responses significantly above baseline at 5 min. In alpha(2A/D)-adrenoceptor knockout mice, the peak response to MDMA (5 mg kg(-1)) was similar to that in wild-type but the response fell to baseline over 5 min with no depressor component, whereas MDMA (20 mg kg(-1)) produced a sustained pressor response significantly above baseline at 10 min. The responses were similar to those obtained in wild-type in the presence of BRL44408. It is concluded that MDMA produces depressor responses in wild-type mice by action at alpha(2A/D)-adrenoceptors to shorten the duration of the pressor response.

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