GABA(A) receptor-targeted drug development-new perspectives in perioperative anesthesia

Introduction: Perioperative anesthesia delivers pre-, intra-, and postoperative care to meet the needs of patients undergoing diagnostic and surgical procedures. Major challenges are patients at the extremes of age and individuals with a pre-existing disease burden. Frequent problems are the development of chronic pain and cognitive dysfunction upon surgery. Current perioperative pharmacotherapy utilizes a number of drugs acting at GABA_A receptors. Area covered: This review evaluates novel formulations and newly designed GABAergic drugs, offering future improvements in perioperative anesthesia, especially for reducing mortality and avoiding cognitive dysfunction and chronic pain as an outcome of surgery. Expert opinion: There are multiple reasons for mounting efforts in the development of novel GABAergic medications. First, requirements in perioperative anesthesia care have substantially changed during the last two decades. In this respect, the dramatic increase in life expectancy is the most important factor. Moreover, research has considerably expanded our knowledge of how drugs in current clinical use act on the molecular level. Almost all ongoing developmental programs choose chemical structures of well-tried agents as a starting point for exploring the properties of structural analogs. This strategy aims to maintain the clinically desired actions of mother compounds while attempting to extinguish adverse side effects.