Binding IC50: 1.76 nM for rGalR2; 879 nM for hGalR1

Galanin is a 29-aa neuropeptide with a complex role in pain processing. Galanin receptor subtypes are present in dorsal root ganglia and spinal cord with a differential distribution. Three galanin receptors, GalR1, GalR2 and GalR3, have been identified and cloned. AR-M1896 is a specific galanin R2 (GalR2) agonist.

In vitro: Additional removal of the glycine residue in position 1 resulted in AR-M1896 with almost unchanged GalR2 affinity and functional activity, and 500-fold selectivity for GalR2-Rs over GalR1-Rs. This compound represents a truly GalR2-selective galanin analog and, thus, could be used as a pharmacological tool to differentiate between these two receptors [1].

In vivo: In normal rats mechanical and cold allodynia of the hindpaw are induced by intrathecal infusion of low-dose galanin. The same effect is seen with equimolar doses of AR-M1896 or AR-M961 (an agonist both at GalR1 and GalR2 receptors). In allodynic Bennett model rats, the mechanical threshold dose-dependently increased after intrathecal injection of a high AR-M961dose, whereas no effect was observed in the control or AR-M1896 group. No effect of either compounds was observed in nonallodynic Bennett model rats [1].

Clinical trial: Up to now, AR-M1896 is still in the preclinical development stage.

Reference:
[1] Liu HX, Brumovsky P, Schmidt R, Brown W, Payza K, Hodzic L, Pou C, Godbout C, H?kfelt T. 
Receptor subtype-specific pronociceptive and analgesic actions of galanin in the spinal cord: selective actions via GalR1 and GalR2 receptors.  Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9960-4.