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	Figure 2. Acute toxicity of IVM and MOX in Mdr1ab(−/−) mice.Acute toxicity was determined by observing survival during a 14-day period after subcutaneous administration of IVM (black square) or MOX (open square) to small groups (2–8 animals) of Mdr1ab(−/−) mice. Extrapolation from the graph yields an estimated LD50 of 0.46 µmol/kg (0.40 mg/kg) and 2.3 µmol/kg (1.47 mg/kg) for IVM and MOX, respectively.
	Figure 3. Absolute brain accumulation of MLs in Mdr1ab(−/−) and wild-type mice as a function of the administrated dose.IVM (filled squares) or MOX (empty squares) was administered to Mdr1ab(−/−) mice or to wild-type mice at increasing doses. Highest doses used for each ML were below the LD50 to ensure a non-lethal effect of the administration. Mice in each group were sacrificed 24 h after treatment and drug concentrations were determined in brain and plasma. Absolute brain accumulation was plotted against the administrated dose in (A) Mdr1ab(−/−) or (B) wild-type mice. A positive and significant linear correlation was observed between brain uptake and the administered dose rate (R2>0.94 in all cases). All measurements are expressed as mean ± S.D. of six animals.
	Figure 4. Concentration-response curves of rat GABA(A) receptor expressed in Xenopus oocytes.(A) Average concentration-response curve for the reference agonist GABA alone. Data were normalized to the maximum GABA-evoked response and fitted to the Hill equation (EC50 = 12.8±0.3 µM, Hill slope = 1.30±0.02. Data are given as mean ± S.E.M. from 3 independent oocytes batches (n = 4 oocytes for each batch). (B) Concentration-dependent potentiation of the GABA receptor, presented as the percentage of the GABA-evoked response at EC10 (2 µM). To analyse the potentiation of the GABA-evoked current induced by IVM or MOX, GABA-responsive oocytes were exposed to 2 µM GABA, followed by washing and then 2 µM GABA in association with increasing concentrations of IVM (n = 8) or MOX (n = 5). Data were fitted to the Hill equation and are given as mean ± S.E.M.
	Figure 1. Comparison of chemical structures of ivermectin and moxidectin.Ivermectin is a mixture of B1a (substituent butyl on C25) and B1b (substituent isopropyl on C25) forms. The majority (more than 90%) of the drug is present as the B1a form.

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