MUSCARINIC INTERACTIONS OF BISINDOLYLMALEIMIDE ANALOGS

We have used radioligand binding studies to determine the affinities o f seven bisindolylmaleimide analogues, six of which are selective inhi bitors 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 m ost potent analogue, with a K-d of 0.6 mu M at M-1 receptors. The weak est compounds, bisindolylmaleimide IV and bisindolylmaleimide V, had K -d values of 100 mu M. If it is necessary to use protein kinase C inhi bitors at concentrations of 10 mu M or more in studies involving musca rinic receptors then bisindolylmaleimide IV may be the most appropriat e inhibitor to use. (C) 1998 Elsevier Science B.V. All rights reserved .