Ketamir-2

Ketamir-2
Clinical data
Other namesKetamir; Oral ketamine analogue; 1-(2-Chlorophenyl)-N-methyl-2-oxocyclopentan-1-amine
Routes of
administration		Oral
Drug classNMDA receptor antagonist
ATC code
  • None
Identifiers
  • 2-(2-chlorophenyl)-2-(methylamino)cyclopentan-1-one
PubChem CID
Chemical and physical data
FormulaC12H14ClNO
Molar mass223.70 g·mol−1
3D model (JSmol)
  • CNC1(CCCC1=O)C2=CC=CC=C2Cl
  • InChI=1S/C12H14ClNO/c1-14-12(8-4-7-11(12)15)9-5-2-3-6-10(9)13/h2-3,5-6,14H,4,7-8H2,1H3
  • Key:DEJMAUCINACUGY-UHFFFAOYSA-N

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. It is the analogue of ketamine in which the 6-membered cyclohexane ring has been replaced with a 5-membered cyclopentane ring. Ketamir-2 is orally active.

Pharmacology

Ketamir-2 is a very low-affinity antagonist of the phencyclidine (PCP) site of the NMDA receptor. Its affinity (IC50Tooltip half-maximal inhibitory concentration) 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). 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. 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. This is in contrast to ketamine, which shows appreciable affinities for a variety of other targets. As such, Ketamir-2 is claimed to be more selective than ketamine.

Whereas ketamine is a substrate for P-glycoprotein and this might impede its absorption and distribution, Ketamir-2 does not bind to this protein. Relatedly, Ketamir-2 shows improved oral bioavailability relative to ketamine and might have better blood–brain barrier permeability. Ketamir-2 displays a pharmacokinetic profile in animals of rapid absorption and short elimination half-life. 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. Ketamir-2 showed antidepressant-like, anxiolytic-like, and analgesic-like effects in animal models.

History

Ketamir-2 is under development by MIRA Pharmaceuticals. As of July 2024, it is in the preclinical research stage of development. In June 2025, the first journal article about Ketamir-2 was published. According to the Drug Enforcement Administration (DEA), Ketamir-2 is not a controlled substance in the United States as of 2024.

See also

References

  1. 1 2 3 "MIRA Pharmaceuticals". AdisInsight. 1 July 2024. Retrieved 28 June 2025.
  2. 1 2 3 "Delving into the Latest Updates on Ketamir-2 with Synapse". Synapse. 31 May 2025. Retrieved 28 June 2025.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Angel I, Perelroizen R, Deffains W, Adraoui FW, Pichinuk E, Aminov E (20 June 2025). "KETAMIR-2, a new molecular entity and novel ketamine analog". Frontiers in Pharmacology. 16. doi:10.3389/fphar.2025.1606976. ISSN 1663-9812. PMC 12231361.
  4. 1 2 3 4 Lhooq M (9 August 2024). "DEA Says This New Oral Ketamine Analog Is Not a Controlled Substance". DoubleBlind Mag. Retrieved 28 June 2025.
  5. ↑ Roth BL, Gibbons S, Arunotayanun W, Huang XP, Setola V, Treble R, et al. (2013). "The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor". PLOS ONE. 8 (3) e59334. Bibcode:2013PLoSO...859334R. doi:10.1371/journal.pone.0059334. PMC 3602154. PMID 23527166.