title: Interactions between levetiracetam and cardiovascular drugs against electroconvulsions in mice.
abstract: BACKGROUND
  Hypertension and heart failure belong to common comorbid conditions with epilepsy so drug interactions between antiepileptics and cardiovascular drugs are possible in clinical practice. The aim of this study was to evaluate the effects of angiotensin AT1 receptor antagonists (losartan potassium and candesartan cilexetil), angiotensin-converting enzyme (ACE) inhibitors (captopril and perindopril arginine) and diuretics (hydrochlorothiazide and ethacrynic acid) on the anticonvulsant activity of levetiracetam (LEV) in mice.
  
  
  METHODS
  The protective action of LEV was examined in the maximal electroshock seizure threshold test. Drugs were administered intraperitoneally (ip). Additionally, combinations of cardiovascular drugs with LEV were tested for adverse effects in the passive avoidance task and the chimney test.
  
  
  RESULTS
  Losartan potassium (50mg/kg), candesartan cilexetil (8mg/kg), captopril (50mg/kg), hydrochlorothiazide (100mg/kg) and ethacrynic acid (100mg/kg) did not affect the anticonvulsant activity of LEV. Perindopril arginine (10mg/kg) raised the convulsive threshold for LEV administered at doses of 100, 300 and 500mg/kg. This interaction could be pharmacodynamic in nature because the brain concentration of LEV remained unchanged by perindopril. The adverse effects of the combined treatment with LEV and cardiovascular drugs were not observed in the passive avoidance task or the chimney test.
  
  
  CONCLUSIONS
  Although experimental data can be hardly extrapolated to clinical practice, it is suggested that perindopril arginine may positively influence the anticonvulsant action of LEV in epileptic patients. The use of losartan potassium, candesartan cilexetil, captopril, hydrochlorothiazide or ethacrynic acid in patients treated with LEV seems neutral regarding its anticonvulsant activity.
authors.affiliation: Department of Physiopathology, Institute of Rural Health, Lublin, Poland. Electronic address: lukaw@mp.pl.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Lukawski
authors.affiliation: Department of Physiopathology, Institute of Rural Health, Lublin, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Raszewski
authors.affiliation: Department of Physiopathology, Institute of Rural Health, Lublin, Poland; Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.
authors.forename: Stanisław J
authors.initials: SJ
authors.lastname: Czuczwar
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004232:Diuretics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004597:Electroshock; D007274:Injections, Intraperitoneal; D000077287:Levetiracetam; D051379:Mice; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D012640:Seizures / Q000188:drug therapy*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000927:Anticonvulsants; D002317:Cardiovascular Agents; D004232:Diuretics; D000077287:Levetiracetam; D010889:Piracetam
keywords: ACE inhibitors; AT(1) antagonists; Diuretics; Electroconvulsions; Levetiracetam