In vitro and antinociceptive profile of HON0001, an orally active NMDA receptor NR2B subunit antagonist

The antinociceptive effects of magnesium sulfate and MK-801 in visceral inflammatory pain model: The role of NO/cGMP/K+ATP pathway

“…In our study, the highest doses of MK-801 (0.03 mg/kg, s.c.) or MS (15 mg/kg, s.c.) did not cause motor impairment, which was verified by means of the rotarod test. This is supported by previous findings that low doses of MS and MK-801 do not induce adverse effect in rats (Boyce et al, 1999;Begon et al, 2000;Suetake-Koga et al, 2006;Yonehara et al, 2002). These data suggest that the analgesic effects may be obtained with MS or MK-801 without exceeding safe doses.…”

“…In the rotarod test, the cut-off time used was 120 s (Suetake- Koga et al, 2006). The time at which the rats fell off the rotating cylinder was recorded.…”

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

“…Preclinical pharmacological (Taniguchi et al, 1997;Boyce et al, 1999;Suetake-Koga et al, 2006) and genetic (Wei et al, 2001;Tan et al, 2005) studies indicate that GluN2B subunit-containing NMDA receptors may be specifically targeted to treat neuropathic pain (Chizh et al, 2001;Wu and Zhuo, 2009). Prompted by these data, the analgesic efficacy of a single dose of CP-101,606 was tested in a small number of patients suffering from pain due to spinal cord injury and monoradiculopathy, and a clinically meaningful reduction in reported pain was observed (Sang et al, 2003).…”

Excitotoxicity and Glaucoma

“…A number of studies demonstrated that ganglion cells are extremely vulnerable to exogenously applied NMDA, which inducesganglion cell degeneration.It has been also shown that NMDA receptor antagonists are neuroprotective in experimental glaucoma models [110][111][112][113][114][115][116][117]. NMDA receptors permit the influx of sodium ions (Na Although all NMDA receptors express the NR1 subunit [122,123,124], NR2 subunits are major determinants of the functional properties of NMDA receptor [125]. Recently, [126] reported the roles of the four different NR2 subtypes (NR2a, NR2b, NR2c, NR2d) in NMDA-induced retinal cell death using mice lacking specific NR2 subunits.…”

“…It has been reported that memantine prevents the loss of retinal ganglion cells in GLAST knockout mice, a model of normal tension glaucoma (NTG), suggesting that NR2d-containing receptors may be involved in ganglion cell loss in glaucoma [125,126]. It was also demonstrated that Mg 2+ regulates the sensitivity of NMDA receptors to memantine [133].…”