Basimglurant (sulfate)

Basimglurant (RG7090; RO4917523) sulfate is a selective, orally active, blood-brain barrier permeable negative allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), with a K_i of 1.4 nM (against [³H]-ABP688 (HY-110141)) and 35.6 nM (against [³H]-MPEP (HY-14609A)). Basimglurant sulfate inhibits mGlu5-mediated signaling pathways and receptor constitutive activity, regulates dopamine levels in the nucleus accumbens, exerts anxiolytic, antidepressant-like, analgesic and arousal-promoting effects, and alters δ-wave power during non-rapid eye movement sleep. Basimglurant sulfate can be used in research on depression, fragile X syndrome, anxiety disorders, etc^[1][2]. In Vitro:Basimglurant sulfate shows low metabolic stability in rat liver microsomes (11 μL/min/mg) and good stability in human liver microsomes (CL <10 μL/min/mg)^[1].
Basimglurant sulfate shows no teratogenic potential in embryonic stem cell assays^[1].
Basimglurant sulfate potently inhibits the binding of [³H]-MPEP to human, mouse and rat mGlu5 receptors, with K_i values of 35.6 nM, 29.5 nM and 33.2 nM for the three receptors, respectively^[2].
Basimglurant sulfate potently inhibits Quisqualate-induced calcium mobilization in human, mouse, and rat mGlu5-expressing HEK293 cells, with IC₅₀ values of 7.0 nM, 8.88 nM, and 7.48 nM, respectively^[2].
Basimglurant sulfate potently inhibits Quisqualate-induced IP accumulation in HEK293 cells expressing human, mouse, and rat mGlu5, with IC₅₀ values of 5.85 nM, 4.98 nM, and 5.93 nM, respectively. It also acts as an inverse agonist of the human mGlu5 receptor, with a corresponding IC₅₀ of 38.1 nM^[2]. In Vivo:Basimglurant (1-3 mg/kg; i.p., once daily for 21 consecutive days) sulfate exhibits significant antidepressant-like activity in rats with anhedonia induced by chronic mild stress^[2].
Basimglurant (10-30 mg/kg; p.o.; administered three times within 24 h) sulfate exerts antidepressant-like effects in the forced swimming test in rats^[2].
Basimglurant (1-30 mg/kg; p.o.; single administration) sulfate induces a brain activity pattern highly similar to that of typical antidepressants in rats^[2].
Basimglurant (0.03-0.3 mg/kg; p.o.; single administration) sulfate exhibits anxiolytic-like activity in the rat Vogel conflict test^[2].
Basimglurant (0.01-1 mg/kg; p.o.; single administration) sulfate exerts anxiolytic effects in a mouse model of stress-induced hyperthermia^[2].
Basimglurant (0.3-1 mg/kg; p.o.; single administration) sulfate exhibits anxiolytic-like activity in the rat conditioned emotional response test^[2].
Basimglurant (0.1-1 mg/kg; p.o.; single administration) sulfate produces anxiolytic-like effects in the fear-potentiated startle test in rats^[2].
Basimglurant (10 mg/kg; p.o.; single administration) sulfate exhibits analgesic activity in the late phase of the formalin-induced pain model in mice^[2].
Basimglurant (0.1-10 mg/kg; subcutaneous injection; single administration) sulfate dose-dependently inhibits cold allodynia in rats with sciatic nerve ligation^[2].
Basimglurant (0.03-0.3 mg/kg; intravenous administration; single dose) sulfate dose-dependently increases the micturition threshold volume in anesthetized rats^[2].
Basimglurant (0.01-0.03 mg/kg; intravenous injection; single administration) sulfate potently reduces the bladder contraction frequency in anesthetized rats^[2].
Basimglurant (0.03-0.3 mg/kg; p.o.; once daily; for 5 consecutive days) sulfate exerts a dose-dependent arousal-promoting effect during the active dark phase of Norwegian rats, reduces rapid eye movement (REM) sleep and non-rapid eye movement (non-REM) sleep, prolongs sleep latency, and enhances the δ-wave power of non-REM sleep^[2].