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	1141080-15-0;
PubChem CID	25256198;
ChemSpider	24750794;
UNII	GWS86V23Q8;
CompTox Dashboard (EPA)	DTXSID40649497 ;
Chemical and physical data
Formula	C22H16ClFN6O
Molar mass	434.86 g·mol−1
3D model (JSmol)	Interactive image;
	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 Ca_v2 type calcium channels. It was developed as a potential analgesic after the discovery that the selective Ca_v2.2 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 Ca_v2.1 and Ca_v2.3 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

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.
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.
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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[pmid20439438-1] 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.

[pmid22188924-2] 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.

[pmid26247695-3] 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.