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Previous reports suggest that the effects of propofol, ketamine, and thiopental on airway tone may be because of modulation of parasympathetic activity. We examined if these anesthetics interact with recombinant human M1-M3 muscarinic receptors expressed in Chinese hamster ovary cells (CHO-M1, M2, and M3) using the displacement of 0.4 nM of l-[N-methyl-3H]scopolamine methyl chloride([3H]NMS). In addition, functional studies were performed by fluorometrically monitoring methacholine (1 mM) stimulated intracellular Ca2+ ([Ca2+]i) responses. Ketamine concentration dependently displaced [3H]NMS binding to CHO-M1, M2, and M3 cells with affinity, pKi (mean Ki) values of 4.34 ± 0.14 (45 μM), 3.53 ± 0.10 (294 μM), and 3.61 ± 0.02 (246 μM), respectively. The effects at M1 were in the clinical range. Ketamine did not affect either basal or methacholine stimulated increase in [Ca2+]i in CHO-M1 cells. Thiopental significantly displaced [3H]NMS binding to M3 (pKi [mean Ki] = 4.12 ± 0.06 [75 μM]) but not M1 or M2 receptors. Thiopental (10−5–10−3 M) concentration dependently inhibited methacholine stimulated increase in [Ca2+]i in CHO-M3 cells. Propofol and barbituric acid did not interact with any muscarinic receptor subtype. We suggest that at the level of [Ca2+]I, thiopental may possess M3 antagonist activity, whereas there are no functional consequences of the interaction of ketamine with the M1 receptor.