JYL 1421 (SC 0030) is an antagonist of TRPV1 receptor (IC50 = 8 nM).

TRPV1:8 nM

JYL 1421(5 min) inhibits the capsaicin (330 nM)-evoked Ca2+ accumulation in a concentration-dependent manner. The inhibitory effect of the lowest concentration (5 nM) of JYL 1421 reaches the level of significance and 1 μM almost abolishes the response, only 3.1±0.65% of the first capsaicin-induced Ca2+ influx could be observed[1].

Intravenous capsaicin injection at 1 and 2 μg/kg causes a temporary blood pressure drop of 47.4±4.7 and 59.6±4.2 mmHg (n=6), respectively. JYL 1421 at 0.4 and 1.6 mg/kg does not induce hypotension but inhibits the capsaicin-induced blood pressure drop in a dose-dependent manner, necessitating higher capsaicin doses to trigger reflex hypotension post-administration. Capsazepine up to 2 mg/kg does not significantly inhibit capsaicin-evoked hypotension. Capsaicin solution (50 μL, 10 μg/mL) instilled into the left eye of rats causes 12.9±1.3 wiping movements within 3 minutes. Pretreatment with JYL 1421 (0.4 or 1 mg/kg i.p.) does not significantly affect wiping behavior, but doses of 2-5 mg/kg reduce the movements dose-dependently with an ID50 value of 4.6 mg/kg. The mean arterial pressure of untreated rats is 109.9±4.2 mmHg (n=6)[1].