1 The thermogenic activity of the serotonin and noradrenaline reuptake inhibitor sibutramine (BTS 54524; Reductil) was investigated by measuring oxygen consumption (VO 2 ) in rats treated with sibutramine or its two pharmacologically-active metabolites. 2 Sibutramine caused a dose-dependent rise in VO 2 , with a dose of 10 mg kg 71 of sibutramine or its metabolites producing increases of up to 30% that were sustained for at least 6 h, and accompanied by signi®cant increases (0.5 ± 1.08C) in body temperature. 3 Based on the accumulation in vivo of radiolabelled 2-deoxy-[3 H]-glucose, sibutramine had little or no eect on glucose utilization in most tissues, but caused an 18 fold increase in brown adipose tissue (BAT). ). 5 The ganglionic blocking agent, chlorisondamine (15 mg kg 71 ), inhibited completely the VO 2 response to the metabolites of sibutramine, but had no eect on the thermogenic response to the b 3 -adrenoceptor-selective agonist BRL 35135. 6 Similar thermogenic responses were produced by simultaneous injection of nisoxetine and uoxetine at doses (30 mg kg 71 ) that had no eect on VO 2 when injected individually. 7 It is concluded that stimulation of thermogenesis by sibutramine requires central reuptake inhibition of both serotonin and noradrenaline, resulting in increased eerent sympathetic activation of BAT thermogenesis via b 3 -adrenoceptor, and that this contributes to the compound's activity as an anti-obesity agent.

Magnesium sulphate was added to conventional medical therapy in the treatment of persistent severe hypotension and wide QRS complex tachyarrhythmia in an 18-year-old woman presenting with a 1200 mg flecainide overdose. Blood pressure was restored with associated resolution of the electrocardiogram abnormalities.