利喷西平

M ₁ , and M ₃ receptor

The presence of muscarinic autoreceptors in human and guinea pig trachea is investigated by comparing the effects of the muscarinic receptor antagonists Pirenzepine (M ₁ ), Methoctramine (M ₂ ), 4-DAMP (M ₃ ), and Rispenzepine (M ₁ /M ₃ ) on cholinergic neural contractile responses evoked by electrical field stimulation (EFS) and [ ³ H]ACh release. The M ₁ , M ₁ /M ₃ , or M ₃ 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 M ₃ 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; pD ₂ value of 7.31±0.15) .