AMG-8562

AMG-8562 is a selective, orally active transient receptor potential vanilloid 1 (TRPV1) modulator that inhibits the activation of rat TRPV1 by Capsaicin (HY-10448), Anandamide (HY-10863) and N-arachidonyldopamine (HY-110018), 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 Vitro:AMG-8562 completely blocks capsaicin (HY-10448)- 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]. In Vivo:AMG-8562 (0.1-3 mg/kg; p.o.; single administration) dose-dependently blocks Capsaicin (HY-10448)-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 (HY-Y0319)-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].