Repositioning Candidate Details
| Candidate ID: | R1409 |
| Source ID: | DB11823 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Esketamine |
| Synonyms: | (-)-Ketamine; (−)-ketamine; (S)-(−)-ketamine; (S)-2-(o-chlorophenyl)-2-(methylamino)cyclohexanone; (S)-ketamine; Esketamine; L-ketamine; S-(-)-Ketamine; S-ketamine |
| Molecular Formula: | C13H16ClNO |
| SMILES: | CN[C@@]1(CCCCC1=O)C1=CC=CC=C1Cl |
| Structure: |
|
| DrugBank Description: | Major depressive disorder (MDD) is a significant cause of disability worldwide and the most common illness preceding suicide , . On March 5, 2019, the nasal spray drug, _esketamine_, also known as _Spravato_ (by Janssen Pharmaceuticals), was approved by the FDA for treatment-resistant major depression. Esketamine is the s-enantiomer of . Ketamine is a mixture of two enantiomers (mirror image molecules). This is the first time that the FDA has approved esketamine for any use. The FDA approved ketamine (Ketalar) in 1970 . Esketamine may prove to be a promising treatment for patients diagnosed with major depressive disorder who have not experienced an improvement in symptoms despite treatment with various medications and therapies. The intranasal route of administration for this drug allows for easy administration and a fast onset of action, which sets it apart from many other antidepressant agents that may take several weeks to take effect. |
| CAS Number: | 33643-46-8 |
| Molecular Weight: | 237.73 |
| DrugBank Indication: | This drug is indicated in conjunction with an oral antidepressant for the treatment of treatment-resistant depression (TRD) in adults . Note: Esketamine is not approved as an anesthetic agent. The safety and effectiveness of esketamine as an anesthetic agent have not been established to this date . |
| DrugBank Pharmacology: | **General effects** Esketamine is considered a central nervous system (CNS) depressant agent. It may cause sedation, dizziness, and lethargy, among other symptoms . This drug has dissociative and antidepressant properties . Acutely, esketamine may impair attention, judgment, thinking, reaction speed, and motor skills. Two placebo-controlled studies were performed to evaluate the effects of ketamine on the ability to drive. The effects of esketamine 84 mg were comparable to placebo at 6 hours and 18 hours post ingestion . **Effects on cardiac electrophysiology** The effect of esketamine (84 mg nasal spray and 0.8 mg/kg esketamine intravenously infused over 40 minutes) on the QTc interval was studied in a randomized, double-blind, placebo-, and positive-controlled (moxifloxacin 400 mg), 4-period, crossover study in 60 healthy volunteers. A marked increase in heart rate (higher than 10 bpm) was measured in subjects receiving intranasal and intravenous esketamine. Summative evidence from both nonclinical and clinical data suggests a lack of clinically relevant QTc prolongation at the normal therapeutic dose of esketamine . **Effects on blood pressure** Eskestamine causes increases in systolic and/or diastolic blood pressure at all therapeutic doses. Peak blood pressure elevation after esketamine administration occurs about 40 minutes after administration and lasts approximately 4 hours . **Cognitive effects** In a study of healthy volunteers, one dose of this agent caused decline in cognitive performance 40 minutes after administration. Compared to subjects ingesting a placebo, esketamine-treated subjects required a higher level of effort to complete assigned cognitive tests at 40 minutes after administration. Cognitive performance and mental effort were found to be similar between esketamine and placebo at 2 hours after administration . Reports of long-term memory or cognitive impairment have been made following repeated ketamine misuse or abuse. No adverse effects of esketamine nasal spray on cognitive function were seen in a one-year open-label safety study. The long-term cognitive effects of esketamine have not been studied for more than a 1 year period, therefore, the risk of cognitive decline with long-term use is not yet confirmed . |
| DrugBank MoA: | Esketamine, the S-enantiomer of racemic ketamine, is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor. The exact mechanism by which esketamine acts as an antidepressant is unknown. The primary circulating metabolite of esketamine (_noresketamine_) shows activity at the same receptor with a weaker affinity . |
| Targets: | NMDA receptor antagonist; Glutamate receptor ionotropic, NMDA 2B antagonist; Elongation factor 2 inhibitor; Brain-derived neurotrophic factor agonist; BDNF/NT-3 growth factors receptor |
| Inclusion Criteria: | Indication associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|