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Herbert, MK; Weis, R; Holzer, P; Roewer, N.
Peristalsis in the Guinea pig small intestine in vitro is impaired by acetaminophen but not aspirin and dipyrone.
ANESTH ANALG. 2005; 100: 120-127. Doi: 10.1213/01.ANE.0000139352.54676.18 [OPEN ACCESS]
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Leading authors Med Uni Graz
Herbert Michael K.
Co-authors Med Uni Graz
Holzer Peter
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Abstract:
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 microM), acetylsalicylic acid (100-300 microM), and dipyrone (10-100 microM) 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 microM and in all segments tested at 100 microM (EC50=6.0 microM). The increase in PPT resulting from 3 microM 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.
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Acetaminophen - pharmacology
Analgesics, Non-Narcotic - pharmacology
Animals - pharmacology
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Aspirin - pharmacology
Comparative Study - pharmacology
Dipyrone - pharmacology
Dose-Response Relationship, Drug - pharmacology
Electrophysiology - pharmacology
Enzyme Inhibitors - pharmacology
Female - pharmacology
Guinea Pigs - pharmacology
In Vitro - pharmacology
Indoles - pharmacology
Intestine, Small - drug effects
Male - drug effects
Methysergide - pharmacology
NG-Nitroarginine Methyl Ester - pharmacology
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Peristalsis - drug effects
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