Evaluation of the relaxant effect of levetiracetam on isolated rat duodenum.
Levetiracetam (LEV) is an approved drug for the treatment of some epileptic disorders. With few and controversial reports addressing its possible pharmacodynamic interactions, the current study aimed at studying the effect of LEV on isolated rat duodenal strips to enlighten its possible intestinal adverse effects using the isolated smooth muscle strips of rat duodenum. LEV showed a dose-dependent inhibition in KCl (80 mm)-induced contractions in normal Tyrode's solution. Moreover, preincubation with LEV (3 mm) in K+-rich/Ca2+-free medium led to a significant decrease in the maximum contractions (Emax) coupled to a right shift of the cumulative CaCl2concentration curves implying a possible Ca2+channel blocking potential. In addition, LEV exhibited a typical noncompetitive inhibition in the cumulative carbachol concentration curves evidenced as a decrease in Emaxwithout the alteration of EC50, thus eliminating any possible role of the muscarinic receptors in the relaxant effect. To rule out other possible relaxant mechanisms, tests were conveyed in Tyrode's solution containing either 100 μm l-NAME or 10 μm glimepiride to test the possible relaxant roles exhibited by nitric oxide (NO) and KATPchannel opening, respectively. None of the tested pathways was involved in LEV-mediated relaxation. Taken altogether, the results of the current study entail that LEV might exert a relaxant effect on intestinal smooth muscles through blocking L-type voltage-operated calcium channels, but not involving either NO release or KATPchannel opening.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
Hesham A
HA
Salem
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
Muhammad Y
MY
Al-Shorbagy
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects*; D015220:Calcium Channels / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects*; D066298:In Vitro Techniques; D000077287:Levetiracetam; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives*; D015221:Potassium Channels / Q000378:metabolism; D017208:Rats, Wistar
D000927:Anticonvulsants; D015220:Calcium Channels; D015221:Potassium Channels; D009569:Nitric Oxide; D000077287:Levetiracetam; D002217:Carbachol; D002122:Calcium Chloride; D010889:Piracetam
calcium; carbachol; glimepiride; isolated rat duodenum; l-NAME; levetiracetam; potassium chloride