SELECTIVE MUSCARINIC M-1 ANTAGONISTS - DRUG DESIGN AND DISCOVERY

Years of clinical research to treat disorders such as peptic ulcers an d obstructive lung disease with the first generation of modestly selec tive M-1 antagonists (e.g. pirenzepine, telenzepine) have been disappo inting. For some indications (chronic obstructive pulmonary disease), nonselective antagonists (ipratropium bromide) have exhibited better c linical efficacy. The advent of a new generation of centrally active a nd highly selective M, antagonists, such as PD150714, spirotramine FC1 594, (-)-S-ET126 and 4-(pyrrotidino)-1-(4-fluoro-phenylcarbamoyloxy)-1 - phenyl-2-butyne (4-F-PhPyMcN), offers new opportunities for using se lective muscarinic agents as therapeutic agents or research tools.