Drug development in anaesthesia: the remifentanil.
Drug development in anaesthesia poses specific challenges. Describing the development of remifentanil highlights some of these. A new drug in anaesthesia must achieve its clinical goals in all patients and significant levels of toxicity are unacceptable. Rather than asking, "What new drugs does the anaesthetist need?" it may be more relevant to pose the question, "How can we design drugs to do things better?". Recent trends in anaesthesia have led to the development of short acting agents--one of these agents, remifentanil, has been designed to provide a mu-opioid receptor agonist with a rapid and predictable offset of action. The insertion of an alkyl ester group into this 4-anilidopiperidine molecule has resulted in a compound which, whilst retaining the desired mu-opioid receptor pharmacology, is susceptible to metabolism by non-specific esterases in the blood and tissues. The rapid onset and offset of action means that the anaesthetist can deliver high doses of opioid resulting in stable anaesthesia and the lack of accumulation ensures that even after prolonged infusion remifentanil does not compromise recovery. This ability to control the anaesthetic process has relevance in both short and long procedures and the unique characteristics of remifentanil may also in the future prove to have utility in the intensive care setting.
Haigh
C G
CG
Metabolic, Cardiovascular and Oncology, Therapeutic Development Group, Glaxo Wellcome, Greenford, UK.
D000758:Anesthesia; D006801:Humans; D010880:Piperidines / Q000493:pharmacokinetics; D000077208:Remifentanil
D010880:Piperidines; D000077208:Remifentanil