Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Herbert, MK; Roth-Goldbrunner, S; Holzer, P; Roewer, N.
Clonidine and dexmedetomidine potently inhibit peristalsis in the Guinea pig ileum in vitro.
Anesthesiology. 2002; 97(6):1491-1499
Doi: 10.1097/00000542-200212000-00022
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- Führende Autor*innen der Med Uni Graz
- Herbert Michael K.
- Co-Autor*innen der Med Uni Graz
- Holzer Peter
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- Abstract:
- Background: Inhibition of intestinal peristalsis is a major side effect of drugs used for anesthesia or for analgesia and sedation of patients in the intensive care unit. This in vitro study examined the effect of clonidine and dexmedetomidine on intestinal peristalsis and analyzed some of their mechanisms of action. Methods: In isolated segments of the guinea pig small intestine, peristalsis was triggered by a perfusion-induced rise of the intraluminal pressure. The peristaltic pressure threshold to elicit a peristaltic wave was used to quantify drug effects on peristalsis. Vehicle (Tyrode's solution), clonidine (10 nM-100 muM), or dexmedetomidine (0.1-100 nM) were added extraserosally to the organ bath. In other series of experiments, clonidine or dexmedetomidine was administered after pretreatment with yohimbine, prazosin, apamin, naloxone, or vehicle. Clonidine was also tested after blockade of NO synthase with L-NAME and in the presence of the inactive enantiomcr D-NAME. Results: Clonidine and dexmedetomidine concentration-dependently increased peristaltic pressure threshold and inhibited peristalsis (clonidine: EC50 = 19.6 muM; dexmedetomidine: EC50 = 12.0 nM). The inhibition caused by clonidine could be prevented by pretreatment with yohimbine, naloxone, and apamin, but not by prazosin, L-NAME, or D-NAME. Inhibition caused by dexmedetomidine was prevented by yohimbine only. Conclusions: The results reveal that clonidine and, much more potently, dexmedetomidine inhibit peristalsis of the guinea pig ileum in vitro. The inhibition is caused by interaction with alpha(2) adrenoceptors and, in the case of clonidine, also involves activation of small conductance Ca2+-activated potassium channels and endogenous opioidergic pathways.
- Find related publications in this database (using NLM MeSH Indexing)
- Adrenergic alpha-Agonists - pharmacology
- Animals -
- Clonidine - pharmacology
- Dexmedetomidine - pharmacology
- Female -
- Guinea Pigs -
- Ileum - drug effects
- Male -
- Peristalsis - drug effects