1-(3-Chlorophenyl)biguanide (hydrochloride)

1-(3-Chlorophenyl)biguanide (m-CPBG) is an agonist of the serotonin (5-HT) receptor subtype 5-HT₃.¹ It selectively binds 5-HT₃ over 5-HT_1A and 5-HT₂ receptors (K_is = 0.002, 10, and 10 µM, respectively) but also binds to high and low affinity sites on the dopamine transporter (DAT; IC₅₀s = 0.4 and 34.8 µM, respectively, in rat caudate putamen synaptosomal membranes).^2,3 m-CPBG induces depolarization of isolated rat vagus nerve and stimulates inositol phosphate formation in rat frontocingulate cortical slices (EC₅₀s = 0.05 and 4.2 µM, respectively).^1,4 It induces bradycardia, an effect that can be reversed by the 5-HT₃ receptor antagonist ondansetron, in anaesthetized cats (ED₅₀ = 20.3 nmol/kg).¹

1.Kilpatrick, G.J., Butler, A., Burridge, J., et al.1-(m-chlorophenyl)-biguanide, a potent high affinity 5-HT3 receptor agonistEur. J. Pharmacol.182(1)193-197(1990) 2.Campbell, A.D., Womer, D.E., and Simon, J.R.The 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide interacts with the dopamine transporter in rat brain synaptosomesEur. J. Pharmacol.290(2)157-162(1995) 3.Higgins, G.A., Joharchi, N., and Sellers, E.M.Behavioral effects of the 5-hydroxytryptamine3 receptor agonists 1-phenylbiguanide and m-chlorophenylbiguanide in ratsJ. Pharmacol. Exp. Ther.264(3)1440-1449(1993) 4.Edwards, E., Hampton, E., Ashby, C.R., et al.5-HT3-like receptors in the rat medial prefrontal cortex: Further pharmacological characterizationBrain Res.733(1)21-30(1996)