What is hydroxynorketamine and what can it bring to neurotherapeutics?. (November 2014)

• Record Type: Journal Article
• Authors: Singh, Nagendra S; Zarate, Carlos A; Moaddel, Ruin; Bernier, Michel; Wainer, Irving W
• Is Part Of: Expert review of neurotherapeutics. Volume 14:Number 11(2014)
• Page Start: 1239
• Page End: 1242
• Publication Date: 2014-11
• Subjects: Neuropharmacology -- Periodicals; 615.7805
• DOI: 10.1586/14737175.2014.971760
• Languages: English
• ISSNs: 1473-7175

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>(<italic>R, S</italic>)-Ketamine was initially developed as an anesthetic agent and its pharmacological properties were determined on the basis of this clinical use. However, pharmacological studies in rat led to the development of the 'Ketamine Paradigm', whereby (<italic>R, S</italic>)-ketamine and its N-demethylated metabolite (<italic>R, S</italic>)-norketamine were deemed the active compounds whereas the other ketamine metabolites were considered inactive. Recent <italic>in vivo</italic> and <italic>in vitro</italic> studies with (<italic>2S, 6S</italic>)-hydroxynorketamine, a previously identified 'inactive' metabolite, have demonstrated that this compound is an active and selective inhibitor of the α7 subtype of the nicotinic acetylcholine receptor and that this activity contributes to the pharmacological responses associated with the antidepressant activity of (<italic>R, S</italic>)-ketamine. Thus, it appears that it is necessary to reassess the 'Ketamine Paradigm' in regards to the use of sub-anesthetic doses of (<italic>R, S</italic>)-ketamine in the treatment of treatment-resistant depression.</p> </abstract>