Synthesis of Anesthetic Ketamine

Key words

ketamines - anesthetic drug - rearrangement

Significance

Ketamine is an anesthetic drug used both in human and veterinary medicine. It acts primarily as a noncompetitive antagonist of the NMDA receptor, but also shows an activating effect on AMPA receptors. Besides its use as a sedative or pain management drug, ketamine has been shown to be a potent short-acting antidepressant. It induces effects similar to phencyclidine (PCP) with reduced behavioral toxicity.

Comment

The key methodology for the synthesis of ketamine is a thermal rearrangement of α-hydroxy imines to α-amino ketones. This was developed by Stevens and co-workers, who also reported on a series of analogs in a patent (US patent 3254124), which included ketamine. Although synthesized as a racemic mixture, the two enantiomers have remarkably different pharmacologies, with (S)-ketamine being a more potent anesthetic and (R)-ketamine being a more potent antidepressant.

Publikationsverlauf

Artikel online veröffentlicht:
17. März 2023