Org 24461
Org 24461 is a selective and brain-penetrant GlyT-1 inhibitor. Org 24461 blocks glycine uptake, reuptake, reverse operation, [3H]glycine efflux and release. Org 24461 enhances NMDA receptor function, modulates striatal monoamine/glutamate levels, and reverses PCP-induced behavioral and electrographic abnormalities. Org 24461 can be used for the research of retinal hypoxia/ischemia, and schizophrenia.
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- No. CAS: 372198-80-6
- Fòrmula: C19H20F3NO3
- Peso molecular:367.36
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Almacenamiento:
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Chemical Information
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Actividad biológica
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GLT1 |
Org 24461 (40 min) potently inhibits glycine uptake in CHO cells stably expressing hGlyT-1b with an IC50 of 100 nM[1][2].
Org 24461 (0.1-30 μM; 20 min) reverses 7-Chlorokynurenic acid (HY-100811)-induced extension of NMDA-mediated spreading depression latency in isolated chicken retina with an IC50 of 0.36 μM, and reduces NMDA (HY-17551)-induced spreading depression latency at 10-30 μM in the absence of 7-chlorokynurenic acid[1].
Org 24461 (0.3 mM; 90 min) potently inhibits oxygen-glucose deprivation-induced [3H]glycine release from isolated chicken retina, while having no effect on basal normoxic glycine efflux[2].
Org 24461 (5 min preincubation; 10 min incubation at 37°C) potently inhibits high-affinity [3H]glycine uptake in rat cerebral cortex synaptosomes (IC50 = 1.3 μM) and rat striatum synaptosomes (IC50 = 1.8 μM)[3].
Org 24461 inhibits [3H]glycine uptake in rat hippocampal P2 synaptosomes with an IC50 of 2.5 μM at a low [3H]glycine concentration, and an IC50 of 28 μM at a high [3H]glycine concentration[4].
Org 24461 does not affect spontaneous [3H]glycine efflux from superfused rat hippocampal slices, but inhibits glycine-stimulated [3H]glycine efflux in the same preparation[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Org 24461 (10 mg/kg; i.p.; single dose; co-administered with Risperidone (HY-11018) 1 mg/kg i.p.) normalizes extracellular striatal dopamine concentrations, maintains elevated extracellular glycine concentrations, and induces a significant increase in extracellular glutamate concentrations in conscious rats[3].
Org 24461 (2-8 mg/kg; i.p.; single dose) inhibits PCP-induced hypermotility in male NMRI mice with an ID50 of 3.8 mg/kg i.p[4].
Org 24461 (3-30 mg/kg; i.p.; single dose) inhibits D-amphetamine-induced hypermotility in male NMRI mice with an ID50 of 13.5 mg/kg i.p[4].
Org 24461 (1-10 mg/kg; i.p.; single dose) dose-dependently reverses PCP-induced EEG power spectral changes in conscious male Wistar rats[4].
Org 24461 (10 mg/kg; i.v.; single dose) significantly reverses the L-701324 (HY-18698)-induced reduction in rat dorsal raphe nucleus single neuron firing rate[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NMRI (male, 25-33 g, phencyclidine/PCP-induced hypermotility model)[4]
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Dosage:2 mg/kg; 4 mg/kg; 8 mg/kg
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Administration:i.p.; single dose
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Result:Dose-dependently inhibited PCP-induced hypermotility, with an ID50 value of 3.8 mg/kg i.p.
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Animal Model:NMRI (male, 25-33 g, D-amphetamine-induced hypermotility model)[4]
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Dosage:3 mg/kg; 10 mg/kg; 30 mg/kg
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Administration:i.p.; single dose
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Result:Dose-dependently inhibited D-amphetamine-induced hypermotility, with an ID50 value of 13.5 mg/kg i.p.
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Animal Model:Wistar (male, 500 g, PCP-induced EEG power spectral change model)[4]
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Dosage:1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:i.p.; single dose
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Result:Dose-dependently attenuated PCP-induced power decrements at higher frequencies (5-30 Hz) in prefrontal and sensorimotor cortices.
Induced synchronization peaks at 3-5 Hz and 8-20 Hz frequency bands in the prefrontal cortex at 10 mg/kg i.p.
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Animal Model:Wistar (male, 250-300 g, neuronal hypofunction induced by NMDA receptor glycineB site blockade)[5]
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Dosage:10 mg/kg
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Administration:i.v.; single dose
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Result:Reversed L-701324-induced inhibition of dorsal raphe nucleus neuron firing, restoring rates from 3.64 Hz to near control levels (7.64 vs. 7.92 Hz) with statistical significance.
Increased firing within 1 minute after injection, peaked at 4–5 minutes, then declined gradually.
Tended to elevate dorsal raphe nucleus neuronal firing when given alone, but the effect was not significant.
Chemical Information
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No. CAS 372198-80-6
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Peso molecular 367.36
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Fòrmula C19H20F3NO3
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SMILES
O=C(CN(CCC(C1=CC=CC=C1)OC2=CC=C(C(F)(F)F)C=C2)C)O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[1]. Kertesz S, et al. Temporal alteration of spreading depression by the glycine transporter type-1 inhibitors NFPS and Org-24461 in chicken retina. Brain Res. 2013;1492:1-6. [Content Brief]
[2]. Harsing LG Jr, et al. Inhibition of hypoxia-induced [(3)H]glycine release from chicken retina by the glycine transporter type-1 (GlyT-1) inhibitors NFPS and Org-24461. Exp Eye Res. 2012;94(1):6-12. [Content Brief]
[3]. Nagy K, et al. Alterations in brain extracellular dopamine and glycine levels following combined administration of the glycine transporter type-1 inhibitor Org-24461 and risperidone. Neurochem Res. 2010;35(12):2096-2106. [Content Brief]
[4]. Harsing LG Jr, et al. The glycine transporter-1 inhibitors NFPS and Org 24461: a pharmacological study. Pharmacol Biochem Behav. 2003;74(4):811-825. [Content Brief]
[5]. Papp A, et al. The synaptic and nonsynaptic glycine transporter type-1 inhibitors Org-24461 and NFPS alter single neuron firing rate in the rat dorsal raphe nucleus. Further evidence for a glutamatergic-serotonergic interaction and its role in antipsychotic action. Neurochem Int. 2008;52(1-2):130-134. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Org 24461 Related Classifications
HY-182484 Related Classifications
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