title: Muscarinic interactions of bisindolylmaleimide analogues.
abstract: 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 M1-M4 receptors. The compounds were most potent at M1 receptors, and Ro-31-8220 was the most potent analogue, with a Kd of 0.6 microM at M1 receptors. The weakest compounds, bisindolylmaleimide IV and bisindolylmaleimide V, had Kd values of 100 microM. If it is necessary to use protein kinase C inhibitors at concentrations of 10 microM or more in studies involving muscarinic receptors then bisindolylmaleimide IV may be the most appropriate inhibitor to use.
authors.affiliation: MRC Collaborative Centre, London, UK. s-lazare@nimr.mrc.ac.uk
authors.forename: S
authors.initials: S
authors.lastname: Lazareno
authors.forename: A
authors.initials: A
authors.lastname: Popham
authors.forename: N J
authors.initials: NJ
authors.lastname: Birdsall
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008301:Maleimides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D011994:Recombinant Proteins; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; C088060:bisindolylmaleimide; C064758:Ro 31-8220