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ketamine analogues with much shorter half-lives would be preferred and could avoid the concomitant use of sedatives and hypnotics.
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Summary: Ketamine is the only highly effective non-opioid anaesthetic and analgesic drug. It has major advantages over opioids (e.g., codeines, fentanyls) in that it shows no respiratory depression or hyperalgesic effects, and is also free of longer term effects such as increased tolerance. Ketamine is primarily an N-methyl-D-aspartate (NMDA)-receptor antagonist with profound sympathomimetic properties. It has a rapid onset of action (distributive time only, <1 min) following intravenous administration, and generates a dissociative anaesthetic state. It has a terminal half-life of 2-3 hours, dictated by its hepatic and renal elimination. The most important adverse effects associated with ketamine are its hallucinogenic properties. It has a relatively long elimination half-life (2-3 hours) and so is usually administered together with sedative or hypnotic drugs, such as midazolam and/or propofol, to try and reduce hallucinations. However, this concomitant use of propofol or midazolam increases the risk of respiratory depression and loss of the patient’s airway. Therefore, ketamine analogues with much shorter half-lives would be preferred and could avoid the concomitant use of sedatives and hypnotics.We have developed very short-acting ketamine analogues with Ketamine Analogues for Anaesthesia anaesthetic efficacy (in-vivo models) and reduced adverse effect profiles compared to ketamine. Applications · Anaesthesia in humans and animals for short procedures in the emergency department · Anaesthesia for longer operations in patients in whom opioids are relatively or absolutely contraindicated · Analgesic sedation for uncomfortable radiological procedures where access to the airway and breathing is difficult · Analgesic sedation for use by paramedics in the field eg. Transport of trauma patients Key Aspects · Short action and reduced adverse effect profile enables increased use compared to ketamine · Reduced use of potentially dangerous adjunctive sedatives or hypnotics · Potential for downstream benefits such as resource savings associated with improved patient recovery times IP Position Provisional Composition of Matter Patent filed 8th October 2012.