M40 is a chimeric galanin-derived peptide and galanin-1 (GAL1) receptor antagonist and GAL2 receptor agonist (Kis = 2.4 and 4.07 nM, respectively).[1],[2] It is selective for the GAL1 and GAL2 receptors over the GAL3 receptor (Ki = 288 nM).[1] M40 induces inositol phosphate accumulation in CHO cells expressing the human GAL2 receptor (EC50 = 16.2 nM) and inhibits forskolin-induced cAMP accumulation in RIN-m5F pancreatic β-cells when used at concentrations of 10 or 100 nM.[1],[2] In vivo, M40 (9.36 nmol/animal, i.c.v.) reverses galanin-induced inhibition of scopolamine-induced hippocampal acetylcholine (ACh) release in conscious rats.[2] M40 reduces galanin-induced increases in food intake in rats. It improves cardiac function and decreases cardiac fibrosis in a rat model of heart failure induced by sustained coronary artery ligation when administered at a dose of 30 nmol/kg.[3] M40 (20 µg/animal) increases the intromission frequency and ejaculation latency in sexually sluggish male mice.[4]
References:
[1].Borowsky, B., Walker, M.W., Huang, L.Y., et al.Cloning and characterization of the human galanin GALR2 receptorPeptides19(10)1771-1781(1998).
[2].Bartfai, T., Langel, Ü., Bedecs, K., et al.Galanin-receptor ligand M40 peptide distinguishes between putative galanin-receptor subtypesProc. Natl. Acad. Sci. USA90(23)11287-11291(1993).
[3].Chen, A., Li, M., Song, L., et al.Effects of the galanin receptor antagonist M40 on cardiac function and remodeling in rats with heart failureCardiovasc. Ther.33(5)288-293(2015).
[4].Benelli, A., Bertolini, A., Zoli, M., et al.Pharmacological manipulation of brain galaninergic system and sexual behavior in male micePsychopharmacology (Berl)160(3)325-330(2002).