Ketamir-2
Pharmaceutical compound
From Wikipedia, the free encyclopedia
Ketamir-2, or simply Ketamir, also known as oral ketamine analogue or as 1-(2-chlorophenyl)-N-methyl-2-oxocyclopentan-1-amine, is an NMDA receptor antagonist closely related ketamine and other arylcyclohexylamines which is under development for the treatment of depressive disorders and other conditions such as neuropathic pain.[1][2][3][4] It is the analogue of ketamine in which the 6-membered cyclohexane ring has been replaced with a 5-membered cyclopentane ring.[3] Ketamir-2 is orally active.[3]
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| Other names | Ketamir; Oral ketamine analogue; 1-(2-Chlorophenyl)-N-methyl-2-oxocyclopentan-1-amine |
| Routes of administration | Oral |
| Drug class | NMDA receptor antagonist |
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| Formula | C12H14ClNO |
| Molar mass | 223.70 g·molâ1 |
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Pharmacology
Ketamir-2 is a very low-affinity antagonist of the phencyclidine (PCP) site of the NMDA receptor.[3] Its affinity (IC50) for the PCP site of the NMDA receptor is approximately 100 μM, whereas that of ketamine (Ki) has been found to be about 660 nM (which is ~150-fold higher affinity).[3][5] Ketamir-2 also has a major active metabolite, desmethylketamir (norketamir), which has an affinity (IC50) for the PCP site of the NMDA receptor of about 470 μM.[3] Ketamir-2 showed no activity at other sites besides the PCP site of the NMDA receptor when screened against a panel of 40 receptors, transporters, enzymes, and ion channels.[3] This is in contrast to ketamine, which shows appreciable affinities for a variety of other targets.[3] As such, Ketamir-2 is claimed to be more selective than ketamine.[3]
Whereas ketamine is a substrate for P-glycoprotein and this might impede its absorption and distribution, Ketamir-2 does not bind to this protein.[3][4] Relatedly, Ketamir-2 shows improved oral bioavailability relative to ketamine and might have better bloodâbrain barrier permeability.[3][4] Ketamir-2 displays a pharmacokinetic profile in animals of rapid absorption and short elimination half-life.[3] Whereas ketamine produces hyperlocomotion in rodents, a stimulant- and putatively psychotic-like effect, Ketamir-2, depending on the dose, either did not affect locomotor activity or decreased it.[3] Ketamir-2 showed antidepressant-like, anxiolytic-like, and analgesic-like effects in animal models.[3]
History
Ketamir-2 is under development by MIRA Pharmaceuticals.[1][2] As of July 2024, it is in the preclinical research stage of development.[1][2] In June 2025, the first journal article about Ketamir-2 was published.[3] According to the Drug Enforcement Administration (DEA), Ketamir-2 is not a controlled substance in the United States as of 2024.[4]