m-Chlorophenylbiguanide hydrochloride

Serotonin (5-hydroxytryptamine, 5-HT) is a monoamine neurotransmitter synthesized from the amino acid tryptophan by the enzyme tryptophan-decarboxylase. The 5-HT3 channel is a ligand gated ion channel receptor of the cys-loop channel family. It is a pentamer with five subunits surrounding a central channel¹.

m-Chlorophenylbiguanide hydrochloride (mCPG) is a prototypical, potent and selective 5-HT3 receptor agonist. In a study conducted in N1E-115 neuroblastoma cells mCPG exhibited inward rectification and reversed currents similar to those induced by 5-HT binding to the 5-HT3 receptor. The rate of receptor desensitization is similar to that of 5-HT binding but the peak current amplitude provoked by the agonist was found to be only 20% at saturating concentration². Interestingly, mCPG seems to facilitate noradrenaline release in mouse brain cortex cell. When mouse brain slices were incubated with H-noradrenaline, electrical field stimulation was facilitated by mCPG and this effect was blocked by the α₂ adrenergic receptor antagonist, Rauwolscine³. mCPG binds and activates recombinant α9/α10 acetylcholine receptors in Xenopus oocytes (although 5-HT does not) thus producing inwards currents that are 3.1±0.7% of the maximum effect obtained by ACh binding⁴.