Polyamines may modulate both G protein-coupled receptors and G proteins.

Polyamines pipertramine (PIP) and pipertramine amide (PIPAM), unlike prototype methoctramine, displayed a potent inotropic effect in guinea pig atria. While the inotropic effect of PIP may be rationalized, as previously suggested, through a direct activation of a Gi/o protein, PIPAM effects were possibly the result of multiple interactions. Besides a direct Gi/o protein activation, PIPAM activated also muscarinic M 2 receptors by interacting most likely with an allosteric site. Binding experiments in CHO cells, expressing human cloned muscarinic M 2 receptors, confirmed that both compounds were effective muscarinic ligands.