Rispenzepine

Rispenzepine is a novel antimuscarinic compound with a preferential action at M₁, and M₃ receptor subtypes. IC50 & Target: M₁, and M₃ receptor^[1] In Vitro: The presence of muscarinic autoreceptors in human and guinea pig trachea is investigated by comparing the effects of the muscarinic receptor antagonists Pirenzepine (M₁), Methoctramine (M₂), 4-DAMP (M₃), and Rispenzepine (M₁/M₃) on cholinergic neural contractile responses evoked by electrical field stimulation (EFS) and [³H]ACh release. The M₁, M₁/M₃, or M₃ antagonists inhibit the EFS-evoked cholinergic contractile response in a concentration-dependent manner (4-DAMP > Rispenzepine > Pirenzepine), whereas Methoctramine facilitates this response at low concentrations (<3 μM). In ACh release studies, the M₃ antagonist has no significant effect, whereas Pirenzepine, Methoctramine, and Rispenzepine significantly increase ACh release in guinea pig trachea. Rispenzepine almost completely inhibits cholinergic, contractile responses at 0.3 μM (92.7±6.2% inhibition, n=6, p<0.05; pD₂ value of 7.31±0.15) ^[1].