Figure 3-24 The concentration-electroencephalographic (EEG) response relationship for four benzodiazepines: midazolam (full agonist, a), bretazenil (partial agonist, b), flumazenil (antagonist, c), and R0 19-4063 (inverse agonist, d). The maximum effect seen in the EEG response correlates with clinical action (full agonist > partial agonist > antagonist > inverse agonist). (Adapted from Shafer S: Principles of pharmacokinetics and pharmacodynamics. In Longnecker DE, Tinker JH, Morgan GE [eds]: Principles and Practice of Anesthesiology, 2nd ed. St. Louis, Mosby-Year Book, 1997, and from Mandema JW, Kuck MT, Danhof M: Differences in intrinsic efficacy of benzodiazepines are reflected in their concentration-EEG effect relationship. Br J Pharmacol 105:164–170, 1992.)