Muscarinic interactions of bisindolylmaleimide analogues

We have used radioligand binding studies to determine the affinities of seven bisindolylmaleimide analogues, six of which are selective inhibitors of protein kinase C, at human muscarinic M 1–M 4 receptors. The compounds were most potent at M 1 receptors, and Ro-31-8220 was the most potent analogue, with a K d of 0.6 μM at M 1 receptors. The weakest compounds, bisindolylmaleimide IV and bisindolylmaleimide V, had K d values of 100 μM. If it is necessary to use protein kinase C inhibitors at concentrations of 10 μM or more in studies involving muscarinic receptors then bisindolylmaleimide IV may be the most appropriate inhibitor to use.