Fig. 2.

Dose–response curves demonstrate equivalent sensitivity to induction of anesthesia despite genetic or pharmacologic impairment of orexin signaling. y axis depicts the fraction of mice that have lost their righting reflex as a function of the log₁₀ of increasing concentrations of isoflurane or sevoflurane. (A) The ED₅₀, also known as the minimum alveolar concentration at which half the mice lose their righting reflex (MAC_LORR), and Hill slopes are equivalent for wild-type mice (open triangles) and orexin/ataxin-3 mice (filled circles) after stepwise increases in isoflurane (black symbols) or sevoflurane (gray symbols). Best-fit sigmoidal dose–response curves are shown for wild-type mice (dashed lines) and for orexin/ataxin-3 mice (solid lines). (B) Equivalent isoflurane dose–response for mice treated with SB-334867-A (open circles) or vehicle (black triangles). Best-fit sigmoidal dose–response curves are shown for vehicle-treated (dashed lines) and for SB-334867-A-treated mice (solid lines). (C) Pharmacodynamic assessment demonstrating identical onset of isoflurane anesthesia in mice treated with vehicle or increasing doses of SB-334867-A.