Inhibitory effect of amitriptyline on contraction of the rat isolated trachea

The effects of amitriptyline, a tricyclic antidepressant, on contractile responses to exogenously applied acetylcholine, endothelin 1 and high K⁺ were examined in the rat isolated trachea. Amitriptyline (0.3–30 μmol/l) produced a shift to the right of the logarithmic acetylcholine concentration-contraction curve without affecting the maximum contraction. Amitriptyline (10–100 μmol/l) significantly reduced the maximal contractile response to endothelin 1. The IC₅₀ values were 10.3 and 30.2 μmol/l for inhibition of the submaximal contractile response to 1 mmol/l acetylcholine and to 50 nmol/l endothelin 1, respectively. Amitriptyline inhibited the high K⁺ (60 mmol/ l)-evoked contraction with an IC₅₀ of 0.225 μmol/l. The inhibitory effect of amitriptyline was unchanged by the K⁺ channel blockers, charybdotoxin (100 nmol/l) and glibenclamide (up to 10 μmol/l). These results indicate that amitriptyline could antagonize the effect of acetylcholine and also exert direct inhibitory effect on muscle contraction of the rat trachea as a nonselective muscle relaxant. © 1997 S. Karger AG, Basel.