Uses
Mavatrep (JNJ-39439335) is an orally active, selective and potent TRPV1 antagonist with high affinity for hTRPV1 channels (Ki=6.5 nM). Mavatrep antagonizes capsaicin-induced Ca2+ influx with an IC50 value of 4.6 nM. Mavatrep can be used in some studies of neuropathic pain[1].
Biological Activity
mavatrep is a potent and orally bioavailable antagonist of trpv1 with ic50 value of 4.6 nm [1][2].transient receptor potential vanilloid-1 (trpv1) is a thermosensitive and nonselective cation channel, and is a member of the trp channel superfamily. the channel is activated by acidic ph (<6.8), thermal stimuli (>43℃), and endogenous lipidic mediators (anandamide and oxidative metabolites of linoleic acid) [1].mavatrep is a potent and orally bioavailable trpv1 antagonist. in hek293 cells that stably express human or rat trpv1 (rtrpv1) channels, mavatrep (1 μm) inhibited capsaicin-induced ca2+ influx with ic50 values of 4.6 nm and 21 nm. in whole-cell patch clamp electrophysiology assay, mavatrep concentration-dependently inhibited the activation of htrpv1 channels by ph (5.0) and capsaicin (1 μm) with ic50 values of 6.8 and 23 nm, respectively. mavatrep (0.1 μm) also inhibited 74 ± 8.1% heat-evoked currents mediated by htrpv1 [1].in the cfa model of inflammatory of pain, mavatrep (10 mg/kg po) significantly reversed cfa-induced thermal hypersensitivity with ed50 and ed80 values of 1.8 and 7.8 mg/kg, respectively [1].
in vivo
Mavatrep (1, 3, 10, 30 mg/kg; p.o.; single) shows complete reversal of thermal hypersensitivity both in CFA model of inflammatory of pain and (0.1, 0.3, 1, 3, 10 mg/kg) carrageenan model of inflammatory pain[1].
Mavatrep (10 mg/kg; p.o.; single) exhibits substantial bioavailability in the rat (51%)[1].
| Animal Model: | Male Sprague-Dawley rats (195-350 g; CFA model of inflammatory of pain)[1]. |
| Dosage: | 10 mg/kg |
| Administration: | Oral administration, single. |
| Result: | Significantly reversed CFA-induced thermal hypersensitivity, beginning 30 min after administration and lasting for at least 3 h. |
| Animal Model: | Male Sprague-Dawley rats (195-350 g; CFA model of inflammatory of pain)[1]. |
| Dosage: | 1, 3, 10, 30 mg/kg |
| Administration: | Oral administration, single. |
| Result: | Exhibited complete reversal of thermal hypersensitivity, with ED50 and ED80 values of 1.8 and 7.8 mg/kg, and the corresponding plasma levels were 41.9 and 270.8 ng/mL, respectively. |
| Animal Model: | Male Sprague-Dawley rats (195-350 g; carrageenan model of inflammatory pain)[1]. |
| Dosage: | 0.1, 0.3, 1, 3, 10 mg/kg |
| Administration: | Oral administration, single. |
| Result: | Completely reversed carrageenan-induced thermal hypersensitivity, with ED50 and ED80 values of 0.18 and 0.48 mg/kg, and the corresponding plasma levels were 3.8 and 9.2 ng/mL, respectively. |
| Animal Model: | Male Sprague-Dawley rats (195-350 g)[1]. |
| Dosage: | 2 mg/kg (for i.v.); 10 mg/kg (for p.o.). (Dissolved in 20% HPβCD) |
| Administration: | Oral administration, single. |
| Result: | 1.19Pharmacokinetic Parameters of Mavatrep in male Sprague-Dawley rats[1].
| IV (2 mg/kg) | PO (10 mg/kg) | | CL (mL/min/kg) | Vss (L/kg) | T1/2 (h) | | Cmax (ng/mL) | AUCmax (ng?h/mL) | T1/2 (h) | F (%) | | 33 | 10 | 3.4 | | 421 | 4203 | 3.8 | 51 |
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References
[1]. parsons wh, calvo rr, cheung w, et al. benzo[d]imidazole transient receptor potential vanilloid 1 antagonists for the treatment of pain: discovery of trans-2-(2-{2-[2-(4-trifluoromethyl-phenyl)-vinyl]-1h-benzimidazol-5-yl}-phenyl)-propan-2-ol (mavatrep). j med chem, 2015, 58(9): 3859-3874.
