Ketamir-2

Last updated

Ketamir-2
Ketamir structure.png
Clinical data
Other namesKetamir; Oral ketamine analogue; 1-(2-Chlorophenyl)-N-methyl-2-oxocyclopentan-1-amine
Routes of
administration 		Oral
Drug class NMDA receptor antagonist
ATC code
  • None
Identifiers
  • 2-(2-chlorophenyl)-2-(methylamino)cyclopentan-1-one
PubChem CID
Chemical and physical data
Formula C12H14ClNO
Molar mass 223.70 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. [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]

Contents

Pharmacology

Ketamir-2 is a very low-affinity antagonist of the phencyclidine (PCP) site of the NMDA receptor. [3] Its affinity (IC50 Tooltip 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). [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 blood–brain 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]

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.
  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.


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