| Identification | Back Directory | [Name]
Pyrazino[2,1-c][1,2,4]thiadiazine, 9-[4-(cyclohexyloxy)phenyl]-3,4-dihydro-7-methyl-, 2,2-dioxide | [CAS]
1358751-06-0 | [Synonyms]
TAK-653
Pyrazino[2,1-c][1,2,4]thiadiazine, 9-[4-(cyclohexyloxy)phenyl]-3,4-dihydro-7-methyl-, 2,2-dioxide | [Molecular Formula]
C19H23N3O3S | [MOL File]
1358751-06-0.mol | [Molecular Weight]
373.47 |
| Chemical Properties | Back Directory | [Boiling point ]
540.8±52.0 °C(Predicted) | [density ]
1.38±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [form ]
Solid | [pka]
1.71±0.40(Predicted) | [color ]
White to yellow | [InChI]
InChI=1S/C19H23N3O3S/c1-14-13-22-11-12-26(23,24)21-19(22)18(20-14)15-7-9-17(10-8-15)25-16-5-3-2-4-6-16/h7-10,13,16H,2-6,11-12H2,1H3 | [InChIKey]
PXJBHEHFVQVDDS-UHFFFAOYSA-N | [SMILES]
S1(=O)(=O)CCN2C=C(C)N=C(C3=CC=C(OC4CCCCC4)C=C3)C2=N1 |
| Hazard Information | Back Directory | [Uses]
Osavampator (TAK-653) is a AMPA receptor positive allosteric modulator. Osavampator selectively binds to AMPA-R in a glutamate-dependent manner and induces Ca2+ influx in hGluA1i CHO cells (EC50 = 3.3 μM). Osavampator improves learning and memory in many models. Osavampator is can be used for the research of depressive disorders[1][2]. | [Biological Functions]
TAK-653 is a selective positive allosteric modulator (PAM) of AMPA receptors exhibiting minimal agonistic activity, elicits an antidepressant-like response while maintaining a favorable safety profile in rat models.
| [in vivo]
Osavampator (0.03-0.3 mg/kg, p.o., single dose) enhances visual learning and memory in normal rats[2].
Osavampator (0.3 mg/kg, p.o., single dose) enhances sustained attention in the poor performing rats[2].
Osavampator (0.06 mg/kg, p.o., single dose) improves working memory in monkeys[2].
Osavampator (1 mg/kg, p.o., single dose) produces antidepressant-like effects in the rat RSBM (reduction of submissive behavior model)[1]. | Animal Model: | Normal rats[2] | | Dosage: | 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg | | Administration: | Oral gavage (p.o.) | | Result: | Improved the novelty discrimination index (NDI). |
| Animal Model: | Poor performing rats[2] | | Dosage: | 0.3 mg/kg | | Administration: | Oral gavage (p.o.) | | Result: | Increased correct responses and decreased omissions in the poor performing rats. |
| Animal Model: | Fasted monkey[2] | | Dosage: | 0.06 mg/kg | | Administration: | Oral gavage (p.o.) | | Result: | Significantly increased delayed match-to-sample (DMTS) accuracy at a 16-s delay interval.
Maintained the beneficial effect 24 h after administration. |
| Animal Model: | submissive behavior model [1] | | Dosage: | 0.1 mg/kg, 1 mg/kg | | Administration: | Oral gavage (p.o.) | | Result: | Led to a significant reduction in dominance levels compared with vehicle treatment starting from the seventh day of treatment and maintained throughout the study period.
Had a significant effect in reducing dominance levels at 0.1 and 1 mg/kg.
|
| [IC 50]
5-LO | [storage]
Store at -20°C | [References]
[1] Hara H, et al. TAK-653, an AMPA receptor potentiator with minimal agonistic activity, produces an antidepressant-like effect with a favorable safety profile in rats [J]. Pharmacology Biochemistry and Behavior, 2021, 211: 173289. DOI:10.1016/j.pbb.2021.173289
[2] Suzuki A, et al. Strictly regulated agonist-dependent activation of AMPA-R is the key characteristic of TAK-653 for robust synaptic responses and cognitive improvement [J]. Scientific Reports, 2021, 11(1): 14532. DOI:10.1038/s41598-021-93888-0
[3] Hara H, et al. TAK-653, an AMPA receptor potentiator with minimal agonistic activity, produces an antidepressant-like effect with a favorable safety profile in rats. Pharmacol Biochem Behav. 2021 Dec;211:173289. DOI:10.1016/j.pbb.2021.173289 |
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