Articles: ketamine-analogs-derivatives.
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Biochemical pharmacology · Jul 2020
ReviewMolecular mechanisms of the rapid-acting and long-lasting antidepressant actions of (R)-ketamine.
Ketamine, an anesthetic developed in the early 1960s, is also a popular abused drug among young people at dance parties and raves and among spiritual seekers, because it produces schizophrenia-like symptoms and dissociation (i.e., out-of-body experience). Regarding mood disorders, ketamine exerts robust antidepressant actions in treatment-resistant patients with depression. Ketamine is a racemic mixture comprising equal parts of (R)-ketamine (or arketamine) and (S)-ketamine (or esketamine). ⋯ A recent RNA-sequencing analysis suggested that the transforming growth factor β1 (TGF-β1) plays a role in the antidepressant effects of (R)-ketamine. A recent pilot study demonstrated that (R)-ketamine had rapid-acting and sustained antidepressant effects in treatment-resistant patients with depression. In this article, the author reviews the mechanisms of the antidepressant actions of the enantiomers of ketamine and its metabolites, (S)-norketamine and (2R,6R)-hydroxynorketamine (HNK) and discusses the role of the brain-gut-microbiota axis and brain-spleen axis in stress-related psychiatric disorders, such as depression.
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Pharmacological reviews · Jul 2018
ReviewKetamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms.
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 effects. ⋯ We examine the evidence supporting the relevance of these targets of ketamine and its metabolites to the clinical effects of the drug. Ketamine metabolites may have broader clinical relevance than was previously considered, given that HNK metabolites have antidepressant efficacy in preclinical studies. Overall, pharmacological target deconvolution of ketamine and its metabolites will provide insight critical to the development of new pharmacotherapies that possess the desirable clinical effects of ketamine, but limit undesirable side effects.
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Review
Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy.
Ketamine is a phencyclidine derivative, which functions primarily as an antagonist of the N-methyl-D-aspartate receptor. It has no affinity for gamma-aminobutyric acid receptors in the central nervous system. Ketamine shows a chiral structure consisting of two optical isomers. ⋯ Besides analgesic properties, ketamine has rapid-acting antidepressant effects, which may be useful in treating therapy-resistant depressive patients. Well-known psychotomimetic and cognitive adverse effects restrict the clinical usefulness of ketamine, even though fewer psychomimetic adverse effects have been reported with S-ketamine in comparison with the racemate. Safety issues in long-term use are yet to be resolved.
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Expert Opin Drug Metab Toxicol · Nov 2012
ReviewPharmacokinetic and pharmacodynamic considerations for NMDA receptor antagonists in the treatment of chronic neuropathic pain.
Chronic neuropathic pain is a debilitating disease caused by a lesion of the somatosensory nervous system. The N-methyl-D-aspartate receptor (NMDAR) plays an important role in the development of this pain state. Proof of efficacy of NMDAR inhibitors in treating neuropathic pain is limited, with the non-selective NMDAR antagonist ketamine being most effective. ⋯ More proof from good-quality randomized clinical trials on the efficacy of NMDAR inhibitors is required. A major advantage of ketamine therapy is the ability of the molecule to induce rapid and potent antidepressant effects. This is relevant taken the fact that chronic pain and depression are closely linked and are often present in the same patient.