title: The ethosuximide-induced hyperpolarization of smooth muscle tissues--a cause of functional changes in the gastrointestinal tract of rats--is provoked by CA(2+)-dependent K(+)-efflux.
abstract: Ethosuximide is an antiepileptic drug successfully used in the treatment of petit mal especially in childhood. Clinical investigations reveal that ethosuximide has a number of adverse side effects on the gastrointestinal tract (GIT) of patients which may include heaviness, anorexia, pains in the region of the stomach, accompanied sometimes with nausea and vomiting. In the present study we attempt to explain the mechanisms of some of the drug's adverse side effects using an experimental animal model. White rats were employed in the experiments during which they were treated daily with ethosuximide (100 mg/kg) for 100 days. We made use of the following methods in the study: 1. Contrast X-rays study of the gastrointestinal tract. 2. Recording of the bioelectric activity of isolated smooth muscle strips using the sucrose-gap method. 3. Recording of the contractile activity of isolated smooth muscle. Characteristic changes occurring after treatment of rats with ethosuximide include atony of the stomach and the intestines, hypertonus in separate duodenal segments, diminished peristaltic activity, and delayed passage at the 24th hour. The drug inhibits the spontaneous contractile activity of isolated smooth muscle strips from rat gastrointestinal tract. In some duodenal preparations is minimised in the presence of apamin, an inhibitor of Ca2+(-dependent) K+ channels (Ka+(Ca)), while in duodenal preparations this effect may undergo a reversion. In the presence of coffeine the action of ethosuximide on the smooth musculature of rat gastrointestinal tract is reduced significantly. We hypothesis that the observed functional changes in the gastrointestinal tract occur as a result of the hyperpolarizing effect of ethosuximide on the gastrointestinal musculature caused by the outcoming K+(CA)-efflux.
authors.affiliation: Department of Physics and Biophysics, University of Medicine, Plovdiv, Bulgaria.
authors.forename: A
authors.initials: A
authors.lastname: Kristev
authors.forename: V
authors.initials: V
authors.lastname: Sirakov
authors.forename: I
authors.initials: I
authors.lastname: Kostadinova
authors.forename: J
authors.initials: J
authors.lastname: Lukanov
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects*; D002118:Calcium / Q000378:metabolism*; D004064:Digestive System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005013:Ethosuximide / Q000009:adverse effects*; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000927:Anticonvulsants; D015221:Potassium Channels; D005013:Ethosuximide; D002118:Calcium