生物活性

• 描述Rotenone is a classical mitochondrial complex I inhibitor that blocks the electron transfer of mitochondrial respiration chain. It inhibits NADH oxidase and NADH/DB oxidoreductase with IC₅₀ values of 5.1 and 28.8 nM, respectively^[1]. Rotenone blocked the proliferation of MCF-7 and Hela cells by inhibiting the reassembly of microtubules with half inhibitory concentrations of 0.4 and 0.2 μM, respectively^[2]. In substantia nigra pars compacta neurons, 1 μM rotenone stimulated a tolbutamide-sensitive outward current (94 pA) accompanied with the accumulation of intracellular [Na⁺] and [Ca²⁺] ^[3]. Rotenone infusion (2 mg/kg/day for 2 days) in Lewis rats resulted in reduced binding of [³H]dihydrorotenone and complex I throughout the brain, while the enzymatic activities of cytochrome oxidase and succinate dehydrogenase remained unaffected. Systemic rotenone infusion (2.5 mg/kg/day) for 7 – 33 days led to progressive nigrostriatal dopaminergic degeneration in the brain. Compared to nigral cell bodies, striatal nerve terminals were affected more severely and earlier by rotenone infusion^[4].
• 作用机制Rotenone is a lipophilic inhibitor for complex I in mitochondrial electron transport chain that blocks the electron transfer from complex I to ubiquinone, thereby inhibiting oxidative phosphorylation and suppressing the synthesis of ATP^[5].

• 动物研究
  剂量	Rat: 2 mg/kg - 3 mg/kg[6] (i.p.); 3 mg/kg[7] (s.c.) Mice: 0.65 mg/kg - 2.6 mg/kg[8] (i.p.); 30 mg/kg, 100 mg/kg (p.o.)
  给药途径	i.p., s.c., p.o.