Biological Activity
binding ic50: 1.76 nm for rgalr2; 879 nm for hgalr1galanin 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].
References
[1] liu hx, brumovsky p, schmidt r, brown w, payza k, hodzic l, pou c, godbout c, hökfelt 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.
