| Stereochemistry | ACHIRAL |
| Molecular Formula | C21H23NO3 |
| Molecular Weight | 337.4122 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)(C)C1=CC=C(C=C1)\C=C\C(=O)NC2=CC=C3OCCOC3=C2
InChI
InChIKey=GZTFUVZVLYUPRG-IZZDOVSWSA-N
InChI=1S/C21H23NO3/c1-21(2,3)16-7-4-15(5-8-16)6-11-20(23)22-17-9-10-18-19(14-17)25-13-12-24-18/h4-11,14H,12-13H2,1-3H3,(H,22,23)/b11-6+
| Molecular Formula | C21H23NO3 |
| Molecular Weight | 337.4122 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 1 |
| Optical Activity | NONE |
AMG-9810, is a TRPV1 (vanilloid receptor 1) antagonist which blocks all known modes of TRPV1 activation, including heat, proton, and endogenous ligand activation. TRPV1 is a membrane-bound cation channel in peripheral sensory neurons. Inhibition of this receptor has been noted to cause anti-inflammatory effects. In murine dorsal root ganglion primary neuron studies, this compound has been shown to block capsaicin-evoked depolarization and calcitonin gene-related peptide release. Screening of AMG 9810 against a panel of G protein-coupled receptors and ion channels indicated selectivity toward TRPV1. In vivo, AMG-9810 is effective at preventing capsaicin-induced eye wiping in a dose-dependent manner, and it reverses thermal and mechanical hyperalgesia in a model of inflammatory pain induced by intraplantar injection of complete Freund's adjuvant. AMG-9810 is the first cinnamide TRPV1 antagonist reported to block capsaicin-induced eye wiping behavior and reverse hyperalgesia in an animal model of inflammatory pain.
CNS Activity
Originator
Approval Year
PubMed
Sample Use Guides
Rats: a dose-dependent decrease of capsaicin-induced
eye wipes was observed at 15 min with all AMG-9810 doses
tested (3, 10, and 30 mg/kg intraperitoneal). In animals
treated with AMG 9810, 30 min before capsaicin treatment,
statistically significant reductions of the number of eye
wipes were observed with 10 and 30 mg/kg AMG-9810.
Route of Administration:
Intraperitoneal
AMG-9810 potently and concentration-dependently inhibited
capsaicin- and proton-induced 45Ca2+ uptake into CHO
cells expressing r/h chimera with IC50 values of 19.1 +/- 7.9
and 90.3 +/- 53.1 nM, respectively. IC50 values for blocking
capsaicin activation of at rat and human TRPV1 were 85.6 +/-39.4 and 24.5 +/- 15.7 nM, respectively. IC50 values
for blocking proton activation of rat and human TRPV1 were
294 +/- 192 and 92.7 +/- 72.8 nM, respectively.
