Ro 46-5934 ameliorates cholinergic transmission by acting at two different regulatory sites by inhibiting AChE, and by blocking a feed-back mechanism (through M2 receptors) that reduce ACh release Nicotinic receptors Choilne // potentiated -6-fold by scopolamine whereas that of Ro 46-5934 was potentiated only 3-fold, as calculated from a comparison of either the areas under the curves or of the maximal effects (Figure 3). This illustrates the above mentioned concepts: (a) by increasing extracellular ACh, AChE inhibitors stimulate M2 receptors and reduce their efficacy in increasing ACh; and (b) the lower degree of potentiation observed for KO 46-5034 in the presence of scopolamine further supports the notion that this compound, in the absence of scopolamine, already partially blocks M2 receptors. Clinical trials in the human will show whether the promising preclinical profile of this compound can be translated into clinical benefits.