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Jaclyn N. Highland

4 papers in the library · 1,428 citations · publishing 2018-2024

Papers

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Ketamine metabolism via hepatic CYP450 isoforms contributes to its sustained antidepressant actions.

Neuropharmacology November 1, 2024 Thi Mai Loan Nguyen, Jean-Philippe Guilloux, Céline Defaix et al. 3 citations

(R,S)-ketamine (ketamine) has rapid and sustained antidepressant (AD) efficacy at sub-anesthetic doses in depressed patients. A metabolite of ketamine, including (2R,6R)-hydroxynorketamine ((6)-HNKs) has been reported to exert antidepressant actions in rodent model of anxiety/depression. To further understand the specific role of ketamine's metabolism in the AD actions of the drug, we evaluated...

(R)-Ketamine exerts antidepressant actions partly via conversion to (2R,6R)-hydroxynorketamine, while causing adverse effects at sub-anaesthetic doses.

British Journal of Pharmacology July 1, 2019 Panos Zanos, Jaclyn N. Highland, Xin Liu et al.

(R)-Ketamine (arketamine) may have utility as a rapidly acting antidepressant. While (R)-ketamine has lower potency than (R,S)-ketamine to inhibit NMDA receptors in vitro, the extent to which (R)-ketamine shares the NMDA receptor-mediated adverse effects of (R,S)-ketamine in vivo has not been fully characterised. Furthermore, (R)-ketamine is metabolised to (2R,6R)-hydroxynorketamine (HNK),...

( 2R,6R )-hydroxynorketamine exerts mGlu 2 receptor-dependent antidepressant actions

Proceedings of the National Academy of Sciences March 13, 2019 Panos Zanos, Jaclyn N. Highland, Brent W. Stewart et al. 153 citations

Significance Despite available medications for depression, currently approved antidepressants take months to exert therapeutic effects, and ∼30% of patients remain treatment resistant. In contrast, a single subanesthetic dose of ketamine exerts rapid (within hours) and sustained antidepressant actions. Preclinical studies indicate that the ketamine metabolite ( 2R , 6R )-hydroxynorketamine [(...

Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms

Pharmacological Reviews June 26, 2018 Panos Zanos, Ruin Moaddel, Patrick J. Morris et al. 1,272 citations

Ketamine, a racemic mixture consisting of (S)- and (R)-ketamine, has been in clinical use since 1970. Although best characterized for its dissociative anesthetic properties, ketamine also exerts analgesic, anti-inflammatory, and antidepressant actions. We provide a comprehensive review of these therapeutic uses, emphasizing drug dose, route of administration, and the time course of these...