IRL-1620 is an effective and selective agonist of endothelin receptor type B (ETB) (Ki: 16 pM).

ETA receptor:19 μM, ETB receptor:16 pM

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

IRL-1620 improves both acquisition (learning) and retention (memory) on the water maze task and enhances angiogenic and neurogenic remodeling. In rat aorta, IRL-1620 (1-100 nM) enhances cytosolic Ca2+ 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. IRL-1620 (1-100 nM) causes contractions of the guinea pig trachea. For IRL 1620, the effective concentration that produces 30 % of 60 mM KCI-induced contraction is estimated to be 28 nM [1]. Rats treated with IRL-1620 obviously decreases the cognitive impairment induced by Aβ. IRL-1620 treatment enhances the number of blood vessels labeled with VEGF compared to vehicle treatment[2]. 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[3].