title: Remimazolam, a short-acting GABA(A) receptor agonist for intravenous sedation and/or anesthesia in day-case surgical and non-surgical procedures.
abstract: Remimazolam (CNS-7056) is a short-acting GABA(A) receptor agonist, under development by PAION, in collaboration with Japanese licensee Ono Pharmaceutical, as an intravenous sedative agent for potential use in day-case procedures, and the induction and maintenance of anesthesia. A member of the benzodiazapene class of drugs, the structure of remimazolam was modified to produce a drug that displays organ-independent metabolism. The incorporation of a carboxylic ester moiety into the benzodiazapene core of remimazolam renders it susceptible to non-specific tissue esterases and it is rapidly metabolized into its pharmacologically inactive metabolite CNS-7054. Preclinical studies in sheep demonstrated that remimazolam produced a more rapid onset of action, and a shorter duration of action, compared with midazolam. In a phase IIa clinical trial evaluating remimazolam as a procedural sedative for upper gastrointestinal endoscopy in patients, the time to recovery from sedation was shorter and more consistent with remimazolam, relative to midazolam. Because of its organ-independent metabolism and rapid and predictable onset and recovery, remimazolam appears to have potential advantages over other currently available short-acting sedatives.
authors.affiliation: University of Wisconsin-Madison, Department of Anesthesiology, School of Medicine and Public Health B6/319 Clinical Sciences Center, 600 Highland Avenue, Madison WI 53792-3272, USA.
authors.forename: William Kirke
authors.initials: WK
authors.lastname: Rogers
authors.forename: Thomas S
authors.initials: TS
authors.lastname: McDowell
mesh_terms: D000556:Ambulatory Surgical Procedures; D018686:Anesthetics, Intravenous / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D015507:Drugs, Investigational / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D058785:GABA-A Receptor Agonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018686:Anesthetics, Intravenous; D014151:Anti-Anxiety Agents; D015507:Drugs, Investigational; D058785:GABA-A Receptor Agonists; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; C522201:remimazolam