Blixeprodil hydrochloride (GM-1020 hydrochloride) is an orally active, blood-brain barrier-penetrant NMDA receptor inhibitor with a K i of 3.25 µM in rat cortical tissues. Blixeprodil hydrochloride binds to the MK-801 ion channel site and blocks NMDA receptor-mediated currents in hyperpolarized states in a voltage-dependent manner. Blixeprodil hydrochloride modulates the power of cortical EEG frequency bands, alters spontaneous motor activity, and induces ataxia at high doses. Blixeprodil hydrochloride can be used in the research of depression [1].
In Vivo, Blixeprodil (GM-1020) (1-32 mg/kg; s.c.; single dose) hydrochloride produces dose-dependent antidepressant-like effects in the rat Forced Swim Test, with maximal efficacy observed at 3.2 mg/kg s.c[1]. Blixeprodil (0.75-9 mg/kg; i.p.; weekly; 5 weeks) hydrochloride reverses CMS-induced depressive-like phenotypes in rats at doses ≥1.5 mg/kg i.p., with effects durable for up to 15 days after the final weekly dose[1]. Blixeprodil (1.5-9 mg/kg; i.p.; single dose; 1-10 mg/kg; p.o.; single dose) hydrochloride restores CMS-induced anhedonia in rats for up to 14 days post-dose[1]. Blixeprodil (1-32 mg/kg; s.c.; single dose) hydrochloride produces motor impairment in rats and mice only at doses ≥ 10 mg/kg s.c., with a 12-fold separation between efficacious plasma exposures for antidepressant-like effects and those causing ataxia in rats[1]. Blixeprodil (1-10 mg/kg; s.c.; single dose) hydrochloride produces dose-dependent changes in rat cortical EEG indicative of NMDA receptor target engagement[1].
In Vitro, Blixeprodil (GM-1020) hydrochloride binds to NMDA receptors in rat brain homogenates with a Ki value of 3.25 µM[1]. Blixeprodil hydrochloride inhibits the functional activities of both NR1/NR2A and NR1/NR2B NMDA receptors in Xenopus laevis oocytes with similar potency, with IC50 values of 3.70 µM and 4.16 µM, respectively[1]. Blixeprodil hydrochloride inhibits NR1/2A NMDA receptor-mediated currents in HEK293 cells with an IC50 of 1.192 µM, and blocks the receptor in a voltage-dependent manner; Blixeprodil hydrochloride binds to the human μ-opioid receptor in transfected HEK cells, with a Ki value of 19 µM[1]. Blixeprodil hydrochloride exhibits selective binding to NMDA receptors across a broad panel of off-targets, with weak binding affinity for the serotonin transporter (Ki = 6.2 µM)[1].
References:
[1]. Klein AK, et al. GM-1020: a novel, orally bioavailable NMDA receptor antagonist with rapid and robust antidepressant-like effects at well-tolerated doses in rodents. Neuropsychopharmacology. 2024 May;49(6):905-914.
In Vivo, Blixeprodil (GM-1020) (1-32 mg/kg; s.c.; single dose) hydrochloride produces dose-dependent antidepressant-like effects in the rat Forced Swim Test, with maximal efficacy observed at 3.2 mg/kg s.c[1]. Blixeprodil (0.75-9 mg/kg; i.p.; weekly; 5 weeks) hydrochloride reverses CMS-induced depressive-like phenotypes in rats at doses ≥1.5 mg/kg i.p., with effects durable for up to 15 days after the final weekly dose[1]. Blixeprodil (1.5-9 mg/kg; i.p.; single dose; 1-10 mg/kg; p.o.; single dose) hydrochloride restores CMS-induced anhedonia in rats for up to 14 days post-dose[1]. Blixeprodil (1-32 mg/kg; s.c.; single dose) hydrochloride produces motor impairment in rats and mice only at doses ≥ 10 mg/kg s.c., with a 12-fold separation between efficacious plasma exposures for antidepressant-like effects and those causing ataxia in rats[1]. Blixeprodil (1-10 mg/kg; s.c.; single dose) hydrochloride produces dose-dependent changes in rat cortical EEG indicative of NMDA receptor target engagement[1].
In Vitro, Blixeprodil (GM-1020) hydrochloride binds to NMDA receptors in rat brain homogenates with a Ki value of 3.25 µM[1]. Blixeprodil hydrochloride inhibits the functional activities of both NR1/NR2A and NR1/NR2B NMDA receptors in Xenopus laevis oocytes with similar potency, with IC50 values of 3.70 µM and 4.16 µM, respectively[1]. Blixeprodil hydrochloride inhibits NR1/2A NMDA receptor-mediated currents in HEK293 cells with an IC50 of 1.192 µM, and blocks the receptor in a voltage-dependent manner; Blixeprodil hydrochloride binds to the human μ-opioid receptor in transfected HEK cells, with a Ki value of 19 µM[1]. Blixeprodil hydrochloride exhibits selective binding to NMDA receptors across a broad panel of off-targets, with weak binding affinity for the serotonin transporter (Ki = 6.2 µM)[1].
References:
[1]. Klein AK, et al. GM-1020: a novel, orally bioavailable NMDA receptor antagonist with rapid and robust antidepressant-like effects at well-tolerated doses in rodents. Neuropsychopharmacology. 2024 May;49(6):905-914.