索伐肽

IC50: 16 pM (Endothelin receptor B), 19 μM (Endothelin receptor A)

IRL-1620 is the most potent and specific ligand for the ETB receptor (K _i ETA/ K _i ETB=120,000) as judged by the K _i values for ETA (19 μM) and ETB (16 PM) receptors. IRL-1620 is 60 times more selective for the ETB receptor than ET-3 (K _i ETA/ K _i ETB=1,900).

IRL-1620 (1-100 nM) induces contractions of the guinea pig trachea. The effective concentration that produces 30 % of 60 mM KCI-induced contraction is estimated to be 28 nM for IRL 1620. IRL-1620 (1-100 nM) increases cytosolic Ca ²⁺ in the vascular endothelium ([Ca]E) with little effect on resting muscle tone, and relaxes the norepinephrine-stimulated tone with an increase in [Ca]E, in rat aorta,. IRL-1620 improves both acquisition (learning) and retention (memory) on the water maze task and enhances angiogenic and neurogenic remodeling. Rats treated with IRL-1620 significantly reduces the cognitive impairment induced by Aβ. IRL-1620 treatment enhances the number of blood vessels labeled with VEGF compared to vehicle treatment. IRL-1620, restores analgesic tolerance to morphine and oxycodone, but it does not affect morphine and oxycodone induced decrease in NGF/PI3K expression. IRL-1620 attenuates opioid tolerance without the involvement of NGF/PI3K pathway.