TROX-1

TROX-1
Identifiers
IUPAC name
  • (3R)-5-(3-chloro-4-fluorophenyl)-3-methyl-3-(pyrimidin-5-ylmethyl)-1-(1H-1,2,4-triazol-3-yl)-1,3-dihydro-2H-indol-2-one
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC22H16ClFN6O
Molar mass434.86 g·mol−1
3D model (JSmol)
SMILES
  • C[C@]5(Cc1cncnc1)C(=O)N(c2nc[nH]n2)c4ccc(c3ccc(F)c(Cl)c3)cc45

TROX-1 is a drug which acts as a potent blocker of the Cav2 type calcium channels. It was developed as a potential analgesic after the discovery that the selective Cav2.2 blocker ziconotide is an active analgesic with similar efficacy to strong opioid drugs. Unlike ziconotide, TROX-1 is not so selective, and also blocks the Cav2.1 and Cav2.3 calcium channel subtypes, but it has the great advantage of being orally active, whereas ziconotide must be administered intrathecally, by injection into the spinal fluid. In animal studies of TROX-1, analgesic effects were observed with similar efficacy to NSAIDs such as naproxen or diclofenac, and anti-allodynia effects equivalent to pregabalin or duloxetine.[1][2][3]

References

  1. ↑ Abbadie C, McManus OB, Sun SY, Bugianesi RM, Dai G, Haedo RJ, et al. (August 2010). "Analgesic effects of a substituted N-triazole oxindole (TROX-1), a state-dependent, voltage-gated calcium channel 2 blocker". The Journal of Pharmacology and Experimental Therapeutics. 334 (2): 545–55. doi:10.1124/jpet.110.166363. PMID 20439438.
  2. ↑ Swensen AM, Herrington J, Bugianesi RM, Dai G, Haedo RJ, Ratliff KS, et al. (March 2012). "Characterization of the substituted N-triazole oxindole TROX-1, a small-molecule, state-dependent inhibitor of Ca(V)2 calcium channels". Molecular Pharmacology. 81 (3): 488–97. doi:10.1124/mol.111.075226. PMID 22188924.
  3. ↑ Rahman W, Patel R, Dickenson AH (October 2015). "Electrophysiological evidence for voltage-gated calcium channel 2 (Cav2) modulation of mechano- and thermosensitive spinal neuronal responses in a rat model of osteoarthritis". Neuroscience. 305: 76–85. doi:10.1016/j.neuroscience.2015.07.073. PMC 4564012. PMID 26247695.
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