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September 5, 2025Open Access

Oral administration of Ketamir-2, a novel ketamine analog, attenuates neuropathic pain in rodent models via selective NMDA antagonism

IAItzchak AngelTeledyne FLIR (United States)RPRita PerelroizenTel Aviv University EPEdward PichinukTel Aviv University

Key Points

Ketamir-2 significantly reduces neuropathic pain in rodent models, outperforming traditional treatments.
In trials, ketamir-2 showed effectiveness in both the Chung spinal nerve ligation and paclitaxel models.
Orally administered ketamir-2 demonstrated superior analgesic effects compared to ketamine and other pain medications.
The study emphasizes that ketamir-2's NMDA antagonism contributes to its efficacy in managing neuropathic pain.

Abstract

Ketamir-2 is a novel ketamine analog with improved oral bioavailability and superior safety profile compared to existing ketamine treatments of pain. It is a low-affinity N-methyl-D-aspartic acid (NMDA) receptor antagonist, which selectively binds to the phencyclidine (PCP) site. Ketamir-2 was evaluated in two pharmacological models of neuropathic pain in rats and mice to evaluate its potential in this disease. These tests included the Chung spinal nerve ligation model in rats and mechanical allodynia in a paclitaxel (PTX)-induced neuropathy model in mice. Ketamir-2, administered orally as the pamoate salt, showed significant effects in both tests at variable doses. In these models, it was more effective than orally administered ketamine, pregabalin, or gabapentin, which were used as a positive control.

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