Copyright © 2009 Informa UK Ltd Not for Sale or Commercial Distribution Unauthorised use prohibited. Authorised users can download, display, view and print a single copy for personal use. Review 10.1517/13543770902765151 © 2009 Informa UK Ltd ISSN 1354-3776 433 All rights reserved: reproduction in whole or in part not permitted Patents related to therapeutic activation of K ATP and K 2P potassium channels for neuroprotection: ischemic/hypoxic/anoxic injury and general anesthetics Susan IV Judge † and Paul J Smith † University of Maryland, School of Medicine, MS Center of Excellence-East, VA Maryland Health Care System, Department of Neurology, BRB 12-040, 655 West Baltimore Street, Baltimore, Maryland 21201, USA Background: Mechanisms of neuroprotection encompass energy deficits in brain arising from insufficient oxygen and glucose levels following respiratory failure; ischemia or stroke, which produce metabolic stresses that lead to unconsciousness and seizures; and the effects of general anesthetics. Foremost among those K + channels viewed as important for neuroprotection are ATP-sensitive (K ATP ) channels, which belong to the family of inwardly rectifying K + channels (K ir ) and contain a sulfonylurea subunit (SUR1 or SUR2) combined with either K ir 6.1 (KCNJ8) or K ir 6.2 (KCNJ11) channel pore-forming α-subunits, and various members of the tandem two-pore or background (K 2P ) K + channel family, including K 2P 1.1 (KCNK1 or TWIK1), K 2P 2.1 (KCNK2 or TREK/TREK1), K 2P 3.1 (KCNK3 or TASK), K 2P 4.1 (KCNK4 or TRAAK), and K 2P 10.1 (KCNK10 or TREK2). Objectives: This review covers patents and patent appli- cations related to inventions of therapeutics, compound screening methods and diagnostics, including K ATP channel openers and blockers, as well as K ATP and K 2P nucleic/amino acid sequences and proteins, vectors, trans- formed cells and transgenic animals. Although the focus of this patent review is on brain and neuroprotection, patents covering inventions of K ATP channel openers for cardioprotection, diabetes mellitus and obesity, where relevant, are addressed. Results/conclusions: Overall, an important emerging therapeutic mechanism underlying neuroprotection is activation/opening of K ATP and K 2P channels. To this end substantial progress has been made in identifying and patenting agents that target K ATP channels. However, current K 2P channels patents encompass compound screening and diagnostics methodo- logies, reflecting an earlier ‘discovery’ stage (target identification/validation) than K ATP in the drug development pipeline; this reveals a wide-open field for the discovery and development of K 2P -targeting compounds. Keywords: ATP-sensitive potassium channels, ischemia, K 2P , K ATP , local anesthetics, neuroprotection, tandem two-pore potassium channels Expert Opin. Ther. Patents (2009) 19(4):433-460 1. Introduction Whether seeking to design and develop therapeutic agents that block/inhibit or open/activate potassium (K + ) channels, it is the ubiquitous distribution of various 1. Introduction 2. KATP channels: neuroprotection, ischemic/hypoxic/anoxic injury, general anesthetics, and glucose homeostasis 3. K2P channels: neuroprotection, ischemic-hypoxic injury and effects of general and local anesthetics 4. KATP patents and patent applications 5. K2P patents and patent applications 6. Expert opinion and conclusions