Remimazolam. Una nueva benzodiazepina de acción ultracorta
Remimazolam: A new ultra short acting benzodiazepine.
Whizar-Lugo V, Garnica-Camacho C, Gastelum-Dagnino R.
J Anesth Crit Care Open Access 2016;4(6)00166.
Remimazolam (CNS 7056) is a novel molecule, water soluble, ultra-short-acting intravenous BDZ under human research in protocols phase II-III. This new BDZ is a designed soft drug, ester-based, intended to undergo rapid hydrolysis by esterase enzymes to inactive metabolites. It acts on GABAA receptors containing gamma subunits, initiating cell membrane hyperpolarization and therefore inhibition of the neural activity via rising chloride influx. After intravenous infusion it rapidly induces sedation for a short period of time with no serious side effects. It has been investigated in the induction and maintenance of general anesthesia, for sedation in gastrointestinal endoscopies, and in the critically ill patient. Like other BDZs, remimazolam can be reversed with flumazenil in order to rapidly terminate sedation if necessary. Because of its organ-independent metabolism, rapid and predictable onset and recovery, remimazolam appears to be the next sedative drug.
Key words: Benzodiazepines, remimazolam, sedation, general anesthesia
Remimazolam (CNS 7056) is a new drug innovation in anesthesia. It combines the properties of two unique drugs already established in anesthesia - Midazolam and remifentanil. It acts on GABA receptors like midazolam and has organ-independent metabolism like remifentanil. It is likely to be the sedative of the future, as preliminary phase II trials have shown minimal residual effects on prolonged infusions. It has potential to be used as a sedative in ICU and as a novel agent for procedural sedation. Unlike most rapidly acting intravenous sedatives available presently, the propensity to cause apnea is very low. Availability of a specific antagonist (flumazenil) adds to its safety even in cases of overdose. The present review discusses remimazolam's potential as a new drug in anesthesia along with the presently available literary evidence.
KEYWORDS: CNS 7056; newer sedatives in anesthesia; remimazolam; soft chemistry in anesthesia
The ideal sedative-hypnotic drug would be a rapidly titratable intravenous agent with a high therapeutic index and minimal side effects. The current efforts to develop such agents are primarily focused on modifying the structures of existing drugs to improve their pharmacodynamic and pharmacokinetic properties. Drugs currently under development using this rational design approach include analogues of midazolam, propofol, and etomidate, such as remimazolam, PF0713, and cyclopropyl methoxycarbonyl-etomidate (MOC-etomidate), respectively. An alternative approach involves the rapid screening of large libraries of molecules for activity in structural or phenotypic assays that approximate anesthetic and target receptor interactions. Such high-throughput screening offers the potential for identifying completely novel classes of drugs. Anesthetic drug development is experiencing a resurgence of interest because there are new demands on our clinical practice that can be met, at least in part, with better agents. The goal of this review is to provide the reader with a glimpse of the novel anesthetic drugs and new developmental approaches that lie on the horizon.