title: ATP sensitive potassium channel openers: A new class of ocular hypotensive agents.
abstract: ATP sensitive potassium (KATP) channels connect the metabolic and energetic state of cells due to their sensitivity to ATP and ADP concentrations. KATPchannels have been identified in multiple tissues and organs of the body including heart, pancreas, vascular smooth muscles and skeletal muscles. These channels are obligatory hetero-octamers and contain four sulfonylurea (SUR) and four potassium inward rectifier (Kir) subunits. Based on the particular type of SUR and Kirpresent, there are several tissue specific subtypes of KATPchannels, each with their own unique set of functions. Recently, KATPchannels have been reported in human and mouse ocular tissues. In ex vivo and in vivo model systems, KATPchannel openers showed significant ocular hypotensive properties with no appearance of toxic side effects. Additionally, when used in conjunction with known intraocular pressure lowering drugs, an additive effect on IOP reduction was observed. These KATPchannel openers have also been reported to protect the retinal ganglion cells during ischemic stress and glutamate induced toxicity suggesting a neuroprotective property for this drug class. Medications that are currently used for treating ocular hypertensive diseases like glaucoma do not directly protect the affected retinal cells, are sometimes ineffective and may show significant side effects. In light of this, KATPchannel openers with both ocular hypotensive and neuroprotective properties, have the potential to develop into a new class of glaucoma therapeutics.
authors.affiliation: Dept. of Ophthalmology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States. Electronic address: roychowdhury.uttio@mayo.edu.
authors.forename: Uttio
authors.initials: U
authors.lastname: Roy Chowdhury
authors.affiliation: Institute for Therapeutics Discovery and Development, Department of Medicinal Chemistry, University of Minnesota, 717 Delaware Street SE, Minneapolis, MN 55414, United States. Electronic address: pidosa@umn.edu.
authors.forename: Peter I
authors.initials: PI
authors.lastname: Dosa
authors.affiliation: Dept. of Ophthalmology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States. Electronic address: fautsch.michael@mayo.edu.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fautsch
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D019806:Cromakalim / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D005901:Glaucoma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D054086:KATP Channels / Q000819:agonists* / Q000378:metabolism; D020108:Nicorandil / Q000494:pharmacology; D014129:Trabecular Meshwork / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D054086:KATP Channels; D019806:Cromakalim; D020108:Nicorandil; D003981:Diazoxide
keywords: ATP sensitive potassium channel openers; Cromakalim; Diazoxide; Glaucoma; Intraocular pressure; Nicorandil; Potassium channel openers; Trabecular meshwork