KETAMIR-2, a new molecular entity and novel ketamine analog
Ketamir-2 is a new molecular entity, and a novel ketamine analog designed to improve oral bioavailability, and offer a superior safety profile compared to existing ketamine treatments. It was found that Ketamir-2 is a low affinity NMDA receptor antagonist, that selectively binds to the PCP site. Its...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-06-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1606976/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849422656169836544 |
|---|---|
| author | Itzchak Angel Rita Perelroizen Wendy Deffains Florian W. Adraoui Eddy Pichinuk Erez Aminov |
| author_facet | Itzchak Angel Rita Perelroizen Wendy Deffains Florian W. Adraoui Eddy Pichinuk Erez Aminov |
| author_sort | Itzchak Angel |
| collection | DOAJ |
| description | Ketamir-2 is a new molecular entity, and a novel ketamine analog designed to improve oral bioavailability, and offer a superior safety profile compared to existing ketamine treatments. It was found that Ketamir-2 is a low affinity NMDA receptor antagonist, that selectively binds to the PCP site. Its IC50 on this receptor site is ∼100 µM. Ketamine acts as an NMDA receptor antagonist (0.5–1 µM affinity) and influences opioid receptors, monoaminergic systems (such as serotonin and dopamine). The selectivity of Ketamir-2 was evaluated across a broad range of receptors, transporters, and binding sites, but no activity was detected. Ketamir-2 is a lower affinity and selective PCP-site NMDA antagonist, compared with ketamine. Upon oral administration, Ketamir-2 does not induce hyperlocomotion in mice. Thus, it is different from Ketamine, which induces marked hyperlocomotion, a behavior which is thought to mimic the psychomotor agitation and disorganized behavior seen in schizophrenia, often linked to disruptions in brain neurotransmitter systems. Ketamir-2 was also evaluated via several pharmacological tests in mice to evaluate its anti-depressive and anxiolytic effects. These tests included the Open Field test (OFT), Elevated Plus Maze (EPM), and Forced Swimming Test (FST); all of which are commonly employed behavioral assays used to evaluate the efficacy of anxiety and depression medications. While showing significant effects in these tests at variable doses, ketamine, which was used as a positive control, did not differ from vehicle treatment or showed an opposite response to Ketamir in the majority of the tests studied. |
| format | Article |
| id | doaj-art-08f0cd0d4c1e40828f29e1526f348f71 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-08f0cd0d4c1e40828f29e1526f348f712025-08-20T03:30:57ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.16069761606976KETAMIR-2, a new molecular entity and novel ketamine analogItzchak Angel0Rita Perelroizen1Wendy Deffains2Florian W. Adraoui3Eddy Pichinuk4Erez Aminov5Mira Pharmaceuticals Inc., Miami, FL, United StatesPharmaseed Ltd., Ness Ziona, IsraelBiotrial, Rennes, FranceBiotrial, Rennes, FrancePharmaseed Ltd., Ness Ziona, IsraelMira Pharmaceuticals Inc., Miami, FL, United StatesKetamir-2 is a new molecular entity, and a novel ketamine analog designed to improve oral bioavailability, and offer a superior safety profile compared to existing ketamine treatments. It was found that Ketamir-2 is a low affinity NMDA receptor antagonist, that selectively binds to the PCP site. Its IC50 on this receptor site is ∼100 µM. Ketamine acts as an NMDA receptor antagonist (0.5–1 µM affinity) and influences opioid receptors, monoaminergic systems (such as serotonin and dopamine). The selectivity of Ketamir-2 was evaluated across a broad range of receptors, transporters, and binding sites, but no activity was detected. Ketamir-2 is a lower affinity and selective PCP-site NMDA antagonist, compared with ketamine. Upon oral administration, Ketamir-2 does not induce hyperlocomotion in mice. Thus, it is different from Ketamine, which induces marked hyperlocomotion, a behavior which is thought to mimic the psychomotor agitation and disorganized behavior seen in schizophrenia, often linked to disruptions in brain neurotransmitter systems. Ketamir-2 was also evaluated via several pharmacological tests in mice to evaluate its anti-depressive and anxiolytic effects. These tests included the Open Field test (OFT), Elevated Plus Maze (EPM), and Forced Swimming Test (FST); all of which are commonly employed behavioral assays used to evaluate the efficacy of anxiety and depression medications. While showing significant effects in these tests at variable doses, ketamine, which was used as a positive control, did not differ from vehicle treatment or showed an opposite response to Ketamir in the majority of the tests studied.https://www.frontiersin.org/articles/10.3389/fphar.2025.1606976/fullketamineketamir-2anti-depressantNMDAneuropathic painhyperlocomotion |
| spellingShingle | Itzchak Angel Rita Perelroizen Wendy Deffains Florian W. Adraoui Eddy Pichinuk Erez Aminov KETAMIR-2, a new molecular entity and novel ketamine analog Frontiers in Pharmacology ketamine ketamir-2 anti-depressant NMDA neuropathic pain hyperlocomotion |
| title | KETAMIR-2, a new molecular entity and novel ketamine analog |
| title_full | KETAMIR-2, a new molecular entity and novel ketamine analog |
| title_fullStr | KETAMIR-2, a new molecular entity and novel ketamine analog |
| title_full_unstemmed | KETAMIR-2, a new molecular entity and novel ketamine analog |
| title_short | KETAMIR-2, a new molecular entity and novel ketamine analog |
| title_sort | ketamir 2 a new molecular entity and novel ketamine analog |
| topic | ketamine ketamir-2 anti-depressant NMDA neuropathic pain hyperlocomotion |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1606976/full |
| work_keys_str_mv | AT itzchakangel ketamir2anewmolecularentityandnovelketamineanalog AT ritaperelroizen ketamir2anewmolecularentityandnovelketamineanalog AT wendydeffains ketamir2anewmolecularentityandnovelketamineanalog AT florianwadraoui ketamir2anewmolecularentityandnovelketamineanalog AT eddypichinuk ketamir2anewmolecularentityandnovelketamineanalog AT erezaminov ketamir2anewmolecularentityandnovelketamineanalog |