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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
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1. Cloning and characterization of the human galanin GALR2 receptor. Peptides 19(10), 1771-1781 (1998).
2. Galanin-
3. Effects of the galanin receptor antagonist M40 on cardiac function and remodeling in rats with heart failure. Cardiovasc. Ther. 33(5), 288-293 (2015).
4. Pharmacological manipulation of brain galaninergic system and sexual behavior in male mice. Psychopharmacology (Berl) 160(3), 325-330 (2002).