Peristalsis in the Guinea Pig Small Intestine In Vitro Is Impaired by Acetaminophen but Not Aspirin and Dipyrone

In Brief Inhibition of intestinal peristalsis is a major side effect of opioid analgesics. It is unknown whether non-opioid analgesics, such as acetaminophen, acetylsalicylic acid, and dipyrone, exert any effect on intestinal motility. In the current in vitro study we examined the effect of these analgesics on intestinal peristalsis and analyzed some of their mechanisms of action. In isolated segments of the guinea pig small intestine peristalsis was triggered by a perfusion-induced increase of the intraluminal pressure. The peristaltic pressure threshold (PPT) at which peristaltic waves were elicited was used to quantify drug effects on peristalsis. Vehicle (Tyrode’s solution), acetaminophen (0.01–100 μM), acetylsalicylic acid (100–300 μM), and dipyrone (10–100 μM) were added extraserosally to the organ bath. Acetaminophen concentration-dependently increased PPT and abolished peristalsis in four of six segments at the concentration of 10 μM and in all segments tested at 100 μM (EC50 = 6.0 μM). The increase in PPT resulting from 3 μM acetaminophen was reduced by naloxone and apamin but not changed by l-nitro-arginine methylester (l-NAME), its inactive enantiomer d-NAME, acetylsalicylic acid, methysergide, or tropisetron. Acetylsalicylic acid and dipyrone did not affect peristalsis. The results reveal, for the first time, that acetaminophen concentration-dependently impairs intestinal peristalsis, whereas acetylsalicylic acid and dipyrone lacked such an effect. The inhibition caused by acetaminophen involves transmitters acting via small conductance Ca2+-activated potassium channels, endogenous opioidergic pathways, and presumably inhibition of cyclooxygenase-3. IMPLICATIONS: Acetaminophen (paracetamol) concentration-dependently impairs peristalsis in the guinea pig small intestine in vitro. The inhibitory action is mediated through activation of endogenous opioidergic pathways, small conductance Ca2+-activated potassium channels, and, presumably, cyclooxygenase -3. Acetylsalicylic acid (aspirin) and dipyrone (metamizol) have no inhibitory effect.