History of anaesthesia: the ketamine story - past, present and future.

: Ketamine's history begins in the 1950s in Detroit, Michigan, at Parke-Davis Laboratories. On 26 March 1956, Harold V. Maddox synthesised phencyclidine or PCP. Domino studied PCP effects in animals and in 1958, Greifenstein made the first trials of PCP in humans under the name of Sernyl. Sernyl did not cause depression of cardiovascular and respiratory functions, but elicited severe excitation with a very prolonged postoperative recovery. Because of its psychedelic effects, it became a street drug under the name of 'angel dust' and was placed on schedule II of Federal Controlled Substance Act (CSA) in 1978. Eticyclidine or PCE had no medical career. The chemist Calvin Stevens, consultant to Parke-Davis, synthesised ketamine in 1962. The drug was studied in humans in 1964, by Domino and Corssen. These authors described the so-called 'dissociative anaesthesia'. Ketamine was patented in 1966 under the name of Ketalar for human use and was administered to soldiers during the Vietnam war. Because of abuse, ketamine was placed among the class III substances of CSA in 1999. The psychedelic effects and the arrival of propofol prompted the shelving of ketamine. However, the discovery of the NMDA-receptor and its noncompetitive inhibition by ketamine revolutionized the pathophysiology of hyperalgesia and mental functioning. In early 1990s, the arrival of remifentanil preceded the discovery of opioid-induced hyperalgesia, eliciting a paradigm shift in the management of pain, and a comeback of ketamine, as and antihyperalgesic drug. Ketamine is nowadays under the spotlight in the field of treatment-resistant depression and has been proposed as a potential fast antidepressant in patients with high suicidal risk. In a near future, we may observe new practices like increased S-(+)-ketamine availability, new ultra-short-acting ketamine analogues or the development antagonists. (C) 2017 European Society of Anaesthesiology

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