ASP8062
ASP8062 is an orally active, blood-brain barrier-permeable selective GABAB receptor positive allosteric modulator. ASP8062 enhances GABA-mediated activation of GABAB receptors and strengthens GABAergic neurotransmission. ASP8062 reverses Reserpine (HY-N0480)-induced myalgia, regulates the sleep-wake cycle, increases delta wave power during non-REM sleep, and impairs motor coordination at high doses. ASP8062 penetrates the central nervous system with a half-life of 40-50 h. ASP8062 can be used in research related to opioid use disorder, fibromyalgia, chronic pain, and alcohol use disorder.
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- CAS No.: 1704716-36-8
- Formule: C20H29N3O2S2
- Masse moléculaire:407.59
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
Description
IC50 & Target
[1]|
GABAB receptor |
In Vitro
ASP8062 acts as a positive allosteric modulator to enhance the potency and maximal response of transfected cell lines stably expressing human or mouse GABAB1c/2 receptors across a wide range of GABA concentrations[2].
ASP8062 exhibits limited to no inhibitory effects on CYP2C9, CYP1A2, CYP2B6, CYP2C8, CYP2C19, CYP2D6, and CYP3A enzymes in human liver microsomes[2].
Metabolism of ASP8062 in liver tissue fractions from mice, rats, rabbits, dogs, monkeys, and humans is mediated primarily by CYP3A4 and secondarily by CYP2D6[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
In Vivo
ASP8062 (0.3-3 mg/kg; p.o.; once daily for 3 consecutive days; 1 hour prior to morphine self-administration) dose-dependently inhibits morphine self-administration behavior in rhesus monkeys, with an IC50 of 0.97 mg/kg, and the 3 mg/kg dose causes a statistically significant reduction in the number of morphine self-administration episodes[1].
ASP8062 (10 mg/kg; p.o.; single administration; administered immediately after subcutaneous injection of 10 mg/kg morphine) does not potentiate morphine-induced respiratory depression in cynomolgus monkeys[1].
ASP8062 (1-10 mg/kg; p.o.; once daily; for 4 consecutive days) significantly reduces all indicators of operant voluntary alcohol intake in male Sprague Dawley rats without inducing non-specific motor effects, with the highest dose yielding the best therapeutic efficacy[4].
ASP8062 (1-10 mg/kg; p.o.; once daily; for 4 consecutive days) significantly reduces operant alcohol self-administration behavior in female Sprague Dawley rats without inducing non-specific motor effects, with the 3 mg/kg and 10 mg/kg doses showing the strongest efficacy in lever pressing and nose poke entry measures[4].
ASP8062 (1-10 mg/kg; p.o.; single administration) modulates the sleep architecture of normal rats at an oral dose of 10 mg/kg, reduces rapid eye movement (REM) sleep and sleep fragmentation, and enhances delta wave power during non-rapid eye movement (NREM) sleep[3].
ASP8062 (3-100 mg/kg; p.o.; single administration) impairs motor coordination in normal rats only at the oral dose of 100 mg/kg[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Rhesus monkeys (adult, 1 male, 2 female, 4.16-6.14 kg)[1]
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Dosage:0.3 mg/kg; 1 mg/kg; 3 mg/kg
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Administration:p.o.; once daily for 3 days; 1 hour prior to morphine self-administration
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Result:Reduced the mean number of morphine self-administrations significantly at 3 mg/kg compared to vehicle-treated controls.
Reached an IC50 value of 0.97 mg/kg.
Showed no gross behavioral signs in any animals during the self-administration period.
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Animal Model:Cynomolgus monkeys (male, 4-6 years old, 4.1-5.3 kg)[1]
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Dosage:10 mg/kg
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Administration:p.o.; single dose; administered immediately after 10 mg/kg morphine s.c.
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Result:Did not produce marked differences in respiratory rate, tidal volume, or minute volume compared to morphine alone.
Did not potentiate morphine-induced reduction in tidal volume (near-significant trend, P=0.06) or statistically significant reduction in minute volume.
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Animal Model:Sprague-Dawley (SD) (male, fibromyalgia model via repeated s.c. reserpine injections)[3]
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Dosage:0.01 mg/kg; 0.03 mg/kg; 0.1 mg/kg; 1 mg/kg; 10 mg/kg; 0.3 mg/kg
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Administration:p.o.; single dose; daily for 6 days
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Result:Significantly reversed the reserpine-induced decrease in muscle pressure threshold at oral doses of 0.03, 0.1, 1, and 10 mg/kg.
Did not produce a significant effect at the 0.01 mg/kg oral dose.
Had its analgesic effect significantly blocked at 0.3 mg/kg p.o. by co-administration of CGP55845 at 3 and 30 mg/kg i.p.
Showed no reduction in analgesic effect after repeated daily administration for 6 days compared to single administration.
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Animal Model:Sprague-Dawley (SD) (male, healthy)[3]
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Dosage:3 mg/kg; 10 mg/kg; 30 mg/kg; 100 mg/kg
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Administration:p.o.; single dose
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Result:Had no significant effect on rotarod retention time at oral doses up to 30 mg/kg.
Significantly reduced time on the rod compared to vehicle-treated rats at 100 mg/kg p.o.
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Animal Model:Sprague-Dawley (SD) (male, healthy, surgically implanted with EEG/EMG electrodes)[3]
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Dosage:1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:p.o.; single dose
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Result:Significantly decreased the percentage of time spent in REM sleep and the frequency of sleep interruptions at 10 mg/kg p.o.
Dramatically increased the power of delta waves (0.5-4 Hz) during non-REM sleep at 10 mg/kg p.o.
Slightly increased the power of theta waves (4-8 Hz) during REM sleep at 10 mg/kg p.o.
Did not produce significant changes to sleep/wake cycle or EEG activity at 1 and 3 mg/kg p.o.
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Animal Model:Sprague Dawley (male, ≥100 days old, initial weight 250−350 gm, chronic intermittent alcohol vapor exposure for 6 weeks, trained to lever press for alcohol under fixed ratio 2 schedule)[4]
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Dosage:1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:p.o.; daily; 4 consecutive days
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Result:Significantly decreased active lever presses (P < 0.001), reinforcers earned (P < 0.01−0.001), head entries (P < 0.01−0.001), and estimated alcohol consumed (g/kg, P < 0.001) compared to vehicle.
Produced a significantly greater reduction in reinforcers earned (P < 0.05) and head entries (P < 0.01) at 10 mg/kg than at 1 mg/kg, and a significantly greater reduction in head entries at 10 mg/kg than at 3 mg/kg (P < 0.05).
Showed no significant differences in inactive lever presses across doses.
Did not alter total distance traveled in open field tests.
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Animal Model:Sprague Dawley (female, ≥100 days old, initial weight 250−350 gm, chronic intermittent alcohol vapor exposure for 6 weeks, trained to lever press for alcohol under fixed ratio 2 schedule)[4]
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Dosage:1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:p.o.; daily; 4 consecutive days
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Result:Significantly decreased active lever presses (P < 0.001) at 3 and 10 mg/kg doses compared to vehicle.
Significantly decreased reinforcers earned (P < 0.05−0.001) across all doses compared to vehicle.
Significantly decreased head entries (P < 0.01) at 3 and 10 mg/kg doses compared to vehicle.
Significantly decreased estimated alcohol consumed (g/kg, P < 0.05−0.001) across all doses compared to vehicle.
Showed no significant differences in inactive lever presses across doses.
Did not alter total distance traveled in open field tests.
Chemical Information
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CAS No. 1704716-36-8
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Masse moléculaire 407.59
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Formule C20H29N3O2S2
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SMILES
O=S1(CCN(CC1)CC2=C3C=C(C4CCC(C)(CC4)C)SC3=NC(C)=N2)=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Akuzawa S, et al. Effect of ASP8062 on morphine self-administration and morphine-induced respiratory suppression in monkeys. Journal of pharmacological sciences. 2023 Apr;151(4):171-176. [Content Brief]
[2]. Walzer M, et al. Single- and Multiple-Dose Safety, Tolerability, and Pharmacokinetic Profiles of ASP8062: Results From 2 Phase 1 Studies. Clinical pharmacology in drug development. 2020 Apr;9(3):297-306. [Content Brief]
[3]. Murai N, et al. A novel GABAB receptor positive allosteric modulator, ASP8062, exerts analgesic effects in a rat model of fibromyalgia. European Journal of Pharmacology. 2020;866:172750. [Content Brief]
[4]. Haile CN, et al. The GABA receptor positive allosteric modulator ASP8062 reduces operant alcohol self-administration in male and female Sprague Dawley rats. Psychopharmacology. 2021 Sep;238(9):2587-2600. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
ASP8062 Related Classifications
HY-184060 Related Classifications
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