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 mumol/l) produced a shift to the right of the logarithmic acetylcholine concentration-contraction curve without affecting the maximum contraction. Amitriptyline (10-100 mumol/l) significantly reduced the maximal contractile response to endothelin 1. The IC50 values were 10.3 and 30.2 mumol/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 mumol/l. The inhibitory effect of amitriptyline was unchanged by the K+ channel blockers, charybdotoxin (100 nmol/l) and glibenclamide (up to 10 mumol/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.
Huang
Y
Y
Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
Lau
C W
CW
D000109:Acetylcholine / Q000494:pharmacology; D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D019332:Endothelin-1 / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D000929:Antidepressive Agents, Tricyclic; D019332:Endothelin-1; D000639:Amitriptyline; D000109:Acetylcholine; D011188:Potassium