AMG-8562 is a selective, orally active transient receptor potential vanilloid 1 ( TRPV1 ) modulator that inhibits the activation of rat TRPV1 by Capsaicin, Anandamide and N-arachidonyldopamine, with IC50 values of 1.75, 9.29 and 3.87 nM, respectively. AMG-8562 blocks capsaicin-induced activation, potentiates pH5-induced activation and has no effect on heat-induced activation of rat TRPV1, whereas it completely blocks capsaicin- and heat-induced activation and partially blocks pH5-induced activation of human TRPV1. AMG-8562 can be used in studies of TRPV1 activation patterns, hyperalgesia and pain-related research [1].
In Vivo, AMG-8562 (0.1-3 mg/kg; p.o.; single administration) dose-dependently blocks Capsaicin -induced withdrawal behavior in rats, achieving 100% blockade at an oral dose of 3 mg/kg[1]. AMG-8562 (30-100 mg/kg; p.o.; single administration) reduces the hyperalgesic window by 27% at oral doses of 30 and 100 mg/kg in a rat model of CFA-induced thermal hyperalgesia[1]. AMG-8562 (30-100 mg/kg; p.o.; single administration) reduces the area of hyperalgesia by 29% at oral doses of 30 and 100 mg/kg in a rat model of heat hyperalgesia induced by plantar skin incision[1]. AMG-8562 (30 mg/kg; p.o.; single administration) significantly reduces acetic acid -induced writhing responses in mice by 59% at an oral dose of 30 mg/kg[1]. AMG-8562 (1-30 mg/kg; p.o.; single dose; 3 mg/kg; i.v.; single dose) does not induce hyperthermia in rats, but causes a mild, dose-dependent decrease in core body temperature, with a maximum reduction of 1.0°C at the 3 mg/kg i.v. dose and 0.6°C at the highest p.o. dose of 30 mg/kg[1]. AMG-8562 (100 mg/kg; p.o.; single administration) does not impair spontaneous locomotor activity in mice or rats at an oral dose of 100 mg/kg, indicating that its analgesic efficacy is not interfered with by sedation or motor impairment[1].
In Vitro, AMG-8562 completely blocks capsaicin - and heat-induced activation of human TRPV1, and partially blocks pH 5-induced activation of human TRPV1[1]. AMG-8562 is selective for TRPV1, with an IC50 of approximately 3 μM against human TRPV4, and IC50 values all >20 μM against rat TRPA1, rat TRPM8, rat TRPV2 and human TRPV3. It also exhibits no partial agonist activity on these channels[1]. AMG-8562 blocks the activation of rat TRPV1 by capsaicin, anandamide, and NADA, with corresponding IC50 values of 1.75 nM, 9.29 nM, and 3.87 nM, respectively. This reagent does not block heat-induced activation, enhances activation under pH 5 conditions, and exhibits no partial agonist activity under physiological pH conditions[1].
References:
[1]. Lehto SG, et al. Antihyperalgesic effects of (R,E)-N-(2-hydroxy-2,3-dihydro-1H-inden-4-yl)-3-(2-(piperidin-1-yl)-4-(trifluoromethyl)phenyl)acrylamide (AMG8562), a novel transient receptor potential vanilloid type 1 modulator that does not cause hyperthermia in rats. Journal of Pharmacology and Experimental Therapeutics. 2008;326(1):218-229.
In Vivo, AMG-8562 (0.1-3 mg/kg; p.o.; single administration) dose-dependently blocks Capsaicin -induced withdrawal behavior in rats, achieving 100% blockade at an oral dose of 3 mg/kg[1]. AMG-8562 (30-100 mg/kg; p.o.; single administration) reduces the hyperalgesic window by 27% at oral doses of 30 and 100 mg/kg in a rat model of CFA-induced thermal hyperalgesia[1]. AMG-8562 (30-100 mg/kg; p.o.; single administration) reduces the area of hyperalgesia by 29% at oral doses of 30 and 100 mg/kg in a rat model of heat hyperalgesia induced by plantar skin incision[1]. AMG-8562 (30 mg/kg; p.o.; single administration) significantly reduces acetic acid -induced writhing responses in mice by 59% at an oral dose of 30 mg/kg[1]. AMG-8562 (1-30 mg/kg; p.o.; single dose; 3 mg/kg; i.v.; single dose) does not induce hyperthermia in rats, but causes a mild, dose-dependent decrease in core body temperature, with a maximum reduction of 1.0°C at the 3 mg/kg i.v. dose and 0.6°C at the highest p.o. dose of 30 mg/kg[1]. AMG-8562 (100 mg/kg; p.o.; single administration) does not impair spontaneous locomotor activity in mice or rats at an oral dose of 100 mg/kg, indicating that its analgesic efficacy is not interfered with by sedation or motor impairment[1].
In Vitro, AMG-8562 completely blocks capsaicin - and heat-induced activation of human TRPV1, and partially blocks pH 5-induced activation of human TRPV1[1]. AMG-8562 is selective for TRPV1, with an IC50 of approximately 3 μM against human TRPV4, and IC50 values all >20 μM against rat TRPA1, rat TRPM8, rat TRPV2 and human TRPV3. It also exhibits no partial agonist activity on these channels[1]. AMG-8562 blocks the activation of rat TRPV1 by capsaicin, anandamide, and NADA, with corresponding IC50 values of 1.75 nM, 9.29 nM, and 3.87 nM, respectively. This reagent does not block heat-induced activation, enhances activation under pH 5 conditions, and exhibits no partial agonist activity under physiological pH conditions[1].
References:
[1]. Lehto SG, et al. Antihyperalgesic effects of (R,E)-N-(2-hydroxy-2,3-dihydro-1H-inden-4-yl)-3-(2-(piperidin-1-yl)-4-(trifluoromethyl)phenyl)acrylamide (AMG8562), a novel transient receptor potential vanilloid type 1 modulator that does not cause hyperthermia in rats. Journal of Pharmacology and Experimental Therapeutics. 2008;326(1):218-229.