We read the letter by Drs. Backman and Deschamps regarding our article. We have demonstrated the antimuscarinic effect of edrophonium by using functional, electrophysiologic, and radioligand binding experiments. Based on the results, we have speculated that the antimuscarinic effect of edrophonium could contribute to less parasympathomimetic effects of the agent compared with those of neostigmine observed in the clinical setting. Against our speculation, Backman and Deschamps stated that edrophonium could reduce cholinergic transmission in autonomic ganglia, and this effect could account for the modest parasympathomimetic effects of edrophonium. The basis of their claim seems to be derived from the article entitled “Heart rate changes in cardiac transplant patients and in the denervated cat heart after edrophonium” by Backman et al. 1As described in their letter, edrophonium failed to block the persistent bradycardia produced by high doses of edrophonium itself in vagus nerve–stimulated cats. Therefore, they concluded that edrophonium did not block the M2receptors in their experimental model. However, we think that there is a serious defect in their statement. If atropine could block the edrophonium-produced persistent bradycardia, the bradycardia would be mediated through the muscarinic receptors, and the antimuscarinic effects of edrophonium, which we have shown, would not work in their model, as they claimed. However, the authors did not examine whether atropine could block the persistent bradycardia produced by edrophonium. If atropine does not block the persistent bradycardia, the underlying mechanism of the persistent bradycardia produced by edrophonium is independent of the muscarinic receptors. As shown in figures 2 and 3 of their article, edrophonium could reduce the heart rate in anesthetized cats with vagotomy and sympathectomy. Again, they did not examine whether atropine could block this edrophonium-produced bradycardia. Rather, it is rational that one thinks that the bradycardic effect of edrophonium in cats with vagotomy and sympathectomy is independent of both parasympathetic and sympathetic nervous systems. Consequently, the results shown in figures 2 and 3 in their article seem to support our speculation. That is, high doses of edrophonium could completely abolish not only the bradycardia produced by the electrical stimulation of vagus nerve but also the bradycardia produced by the anticholinesterase activity of edrophonium by means of its antimuscarinic effect. Backman and Deschamps also cited the report that edrophonium decreased the action potential amplitude recorded from postganglionic axons in the rat sympathetic superior cervical ganglion. 2However, this result indicates that edrophonium could produce bradycardia by inhibiting sympathetic nervous activity, resulting in an augmentation of its bradycardic effect. We understand that they intended to speculate that edrophonium could inhibit the transmission in the parasympathetic ganglion as in the sympathetic ganglion. However, what happens when edrophonium inhibits the parasympathetic ganglion and sympathetic ganglion simultaneously? In conclusion, there is no obvious evidence that edrophonium inhibits the autonomic transmission in the parasympathetic ganglia and that this effect weakens its parasympathomimetic effects produced by cholinesterase inhibition.