Basimglurant sulfate
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Basimglurant (RG7090; RO4917523) sulfate is a selective, orally active, blood-brain barrier permeable negative allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), with a Ki 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.
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- CAS No.: 1034442-21-1
- 화학식: C18H15ClFN3O4S
- 분자량:423.85
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보관:
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Biological Activity
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Chemical Information
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Publications Citing Use of MedChemExpress (MCE) Basimglurant sulfate
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Biological Activity
제품 설명
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 Ki 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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. .
Parmacokinetics
| Species | Dose | Route | Note | Cmax | Tmax | AUC0-∞ | Bioavailability | CL | Vss | T1/2 |
|---|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 1 mg/kg | i.v. | / | / | / | / | / | 5.9 mL/min/kg | 4.0 L/kg | 9.7 h |
| Rat[1] | 10 mg/kg | p.o. | / | 1580 ng/mL | 6.2 h | 25600 ng·h/mL | 91 % | / | / | / |
| Rat[1] | 1.0 mg/kg | i.v. | / | / | / | / | / | 9.1 mL/min/kg | 5.1 L/kg | 10 h |
| Cynomolgus Monkey[1] | 0.3 mg/kg | p.o. | fasted | 76.5 ng/mL | 1.0 h | 852 ng·h/mL | ~100 % | / | / | / |
| Cynomolgus Monkey[1] | 0.3 mg/kg | p.o. | fed | 36.1 ng/mL | 2.0 h | 298 ng·h/mL | 54 % | / | / | / |
In Vivo
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Wistar rats (male, 350 g, chronic mild stress-induced anhedonia model with unilateral ventral tegmental area electrode implantation)[2]
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Dosage:1 mg/kg; 3 mg/kg
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Administration:i.p.; daily; 21 days
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Result:Reduced the anhedonia index by -72% (day 35), -53% (day 39), and -64% (day 42) compared to vehicle-treated stressed rats at 3 mg/kg, normalizing values to pre-stress baseline levels.
Reduced the anhedonia index significantly with consistent effects across the treatment period at 1 mg/kg.
Had no significant effect on anhedonia index in unstressed rats.
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Animal Model:Wistar rats (female, 100-130 g, forced swim test model)[2]
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Dosage:10 mg/kg; 30 mg/kg
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Administration:p.o.; 3 doses over 24 hours (24 h, 16 h, 2 h pre-test)
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Result:Reduced immobility time by -19% at 10 mg/kg and -16% at 30 mg/kg compared to vehicle-treated rats.
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Animal Model:Fischer F344 rats (male, ~250 g, fMRI-based brain activity profiling model)[2]
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Dosage:1 mg/kg; 10 mg/kg; 30 mg/kg
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Administration:p.o.; single dose; 1 hour pre-fMRI imaging
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Result:Increased perfusion in the dorsal striatum and decreased perfusion in the medial prefrontal cortex, dorsal hippocampus, thalamus, hypothalamus, septum, nucleus accumbens, ventral pallidum, and entorhinal piriform cortex at 1 mg/kg.
Amplified the perfusion changes observed at 1 mg/kg at 10 mg/kg.
Showed a pattern match coefficient (PMC) of >0.71 compared to prototypical antidepressants including duloxetine, reboxetine, imipramine, bupropion, and electroconvulsive treatment (ECT) at 1 and 10 mg/kg.
Surpassed the root mean square (RMS) response strength of ECT and standard antidepressants at 30 mg/kg at 1 and 10 mg/kg.
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Animal Model:Sprague Dawley rats (male, 190-210 g, Vogel conflict drinking test model)[2]
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Dosage:0.03 mg/kg; 0.1 mg/kg; 0.3 mg/kg
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Administration:p.o.; single dose; 1 hour pre-test
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Result:Increased punished drinking time by +165% at 0.03 mg/kg, with further increases at higher doses, reaching significance at all tested doses compared to vehicle.
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Animal Model:NMRI mice (male, ~22 g, stress-induced hyperthermia model)[2]
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Dosage:0.01 mg/kg; 0.1 mg/kg; 1 mg/kg
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Administration:p.o.; single dose; 1 hour pre-test
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Result:Reduced stress-induced hyperthermia by -48% at 0.01 mg/kg, -73% at 0.1 mg/kg, and -145% at 1 mg/kg compared to vehicle, with all doses producing significant effects.
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Animal Model:Sprague Dawley rats (male, 350 g, conditioned emotional response model)[2]
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Dosage:0.3 mg/kg; 1 mg/kg
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Administration:p.o.; single dose; 1 hour pre-test
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Result:Increased the suppression ratio by +567% at 0.3 mg/kg and +583% at 1 mg/kg compared to vehicle, indicating reduced fear response.
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Animal Model:Sprague Dawley rats (male, 225-287 g, fear-potentiated startle model)[2]
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Dosage:0.1 mg/kg; 1 mg/kg
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Administration:p.o.; single dose; 1 hour pre-test
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Result:Reduced fear-potentiated startle amplitude by -53% at 0.1 mg/kg and -94% at 1 mg/kg compared to vehicle, with significant effects at both doses.
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Animal Model:NMRI mice (male, 24-30 g, formalin-induced paw licking model, late phase)[2]
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Dosage:1 mg/kg; 10 mg/kg
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Administration:p.o.; single dose; 40 minutes pre-formalin injection
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Result:Reduced paw licking time by -91% (non-significant) at 1 mg/kg and -95% (significant) at 10 mg/kg compared to vehicle in the late phase of formalin-induced pain.
Had no significant effect in the early phase at any tested dose.
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Animal Model:Sprague Dawley rats (female, 100-250 g, Bennett model of cold allodynia with sciatic nerve constriction injury)[2]
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Dosage:0.1 mg/kg; 0.3 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:s.c.; single dose; 60 minutes pre-test
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Result:Increased the inhibition rate of cold allodynia by 28% at 0.1 mg/kg, 37% at 0.3 mg/kg, 50% at 1 mg/kg, 39% at 3 mg/kg, and 58% at 10 mg/kg compared to vehicle.
Produced significant effects at all doses, with maximal efficacy comparable to morphine (64% inhibition rate) and duloxetine (56% inhibition rate).
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Animal Model:Sprague Dawley rats (female, 200-250 g, volume-induced micturition reflex model with cannulated bladders, anesthetized)[2]
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Dosage:0.03 mg/kg; 0.3 mg/kg
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Administration:i.v.; single dose
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Result:Increased the micturition threshold volume by +27% at 0.03 mg/kg and +166.9% at 0.3 mg/kg compared to baseline, with significant effects at both doses.
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Animal Model:Sprague Dawley rats (female, 200-250 g, isovolumetric bladder contraction model with cannulated bladders, anesthetized)[2]
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Dosage:0.01 mg/kg; 0.03 mg/kg
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Administration:i.v.; single dose
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Result:Reduced bladder contraction frequency by -88.5% at 0.01 mg/kg and -79.9% at 0.03 mg/kg compared to vehicle, with maximal effects comparable at both doses.
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Animal Model:Sprague Dawley rats (male, 275-325 g, telemetric EEG/EMG recording model in freely moving rats)[2]
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Dosage:0.03 mg/kg; 0.1 mg/kg; 0.3 mg/kg
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Administration:p.o.; daily; 5 days, administered at ZT 14
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Result:Reduced the REM/non-REM sleep ratio during the dark phase by up to 67% at 0.3 mg/kg.
Reduced time spent in REM sleep by up to 100% (0.1 mg/kg) and non-REM sleep by up to 94% (0.1 mg/kg) during the dark phase.
Increased latency to REM sleep onset by up to +351% and non-REM sleep onset by up to +226% at 0.3 mg/kg.
Increased wakefulness by up to 136% (0.3 mg/kg) and locomotor activity by up to +200% (0.3 mg/kg) during the dark phase, with no subsequent hypersomnolence.
Increased delta power by up to +307% at 0.3 mg/kg during non-REM sleep in the dark phase, an effect that persisted into the light phase.
Chemical Information
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CAS No. 1034442-21-1
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분자량 423.85
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화학식 C18H15ClFN3O4S
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SMILES
O=S(O)(O)=O.FC1=CC=C(N2C(C)=NC(C#CC3=CC(Cl)=NC=C3)=C2C)C=C1
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Synonyms
RG7090 sulfate; RO4917523 sulfate
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
Publications (1)
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Journal Impact Factor
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Most Recent
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ACS Chem Neurosci
Location and Cell-Type-Specific Bias of Metabotropic Glutamate Receptor, mGlu5, Negative Allosteric Modulators. [Abstract]2019 Nov 20;10(11):4558-4570. PMID: 31609579
순도&문서
References
[1]. Jaeschke G, et al. Metabotropic glutamate receptor 5 negative allosteric modulators: discovery of 2-chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl]pyridine (basimglurant, RO4917523), a promising novel medicine for psychiatric diseases. J Med Chem. 2015;58(3):1358-1371. [Content Brief]
[2].
Lindemann L, et al. Pharmacology of basimglurant (RO4917523, RG7090), a unique metabotropic glutamate receptor 5 negative allosteric modulator in clinical development for depression. J Pharmacol Exp Ther. 2015 Apr;353(1):213-33.
[Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Basimglurant sulfate Related Classifications
HY-114515 Related Classifications
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