Selective muscarinic M-1 antagonists: Drug design and discovery

Years of clinical research to treat disorders such as peptic ulcers and obstructive lung disease with the first generation of modestly selective M-1 antagonists (e.g. pirenzepine, telenzepine) have been disappointing. For some indications (chronic obstructive pulmonary disease), nonselective antagonists (ipratropium bromide) have exhibited better clinical efficacy. The advent of a new generation of centrally active and highly selective M, antagonists, such as PD150714, spirotramine FC1594, (-)-S-ET126 and R-4-(pyrrotidino)-1-(4-fluoro-phenylcarbamoyloxy)-1- phenyl-2-butyne (4-F-PhPyMcN), offers new opportunities for using selective muscarinic agents as therapeutic agents or research tools.