title: Effect of Combined Treatment with AT1 Receptor Antagonists and Tiagabine on Seizures, Memory and Motor Coordination in Mice.
abstract: BACKGROUND
  Losartan and telmisartan, angiotensin AT1 receptor antagonists, are widely used antihypertensive drugs in patients. It is also known that arterial hypertension is often present in people with epilepsy, therefore, drug interactions between AT1 receptor antagonists and antiepileptic drugs can occur in clinical practice.
  
  
  OBJECTIVE
  The aim of the current study was to assess the effect of losartan and telmisartan on the anticonvulsant activity of tiagabine, a second-generation antiepileptic drug, in mice. Additionally, the effect of the combined treatment with AT1 receptor antagonists and TGB on long-term memory and motor coordination has been assessed in animals.
  
  
  METHODS
  The study was performed on male Swiss mice. Convulsions were examined in the maximal electroshock seizure threshold test. Long-term memory was measured in the passive-avoidance task and motor coordination was evaluated in the chimney test. AT1 receptor antagonists and TGB were administered intraperitoneally.
  
  
  RESULTS
  Losartan (50 mg/kg) or telmisartan (30 mg/kg) did not influence the anticonvulsant activity of TGB applied at doses of 2, 4 and 6 mg/kg. However, both AT1 receptor antagonists in combinations with TGB (6 mg/kg) impaired motor coordination in the chimney test. The concomitant treatment of the drugs did not decrease retention in the passive avoidance task.
  
  
  CONCLUSIONS
  It is suggested that losartan and telmisartan should not affect the anticonvulsant action of TGB in people with epilepsy. Because the combined treatment with AT1 receptor antagonists and TGB led to neurotoxic effects in animals, caution is advised during concomitant use of these drugs in patients.
authors.affiliation: Department of Physiopathology, Institute of Rural Health, Lublin, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Łukawski
authors.affiliation: Department of Physiopathology, Institute of Rural Health, Lublin, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Janowska
authors.affiliation: Department of Physiopathology, Institute of Rural Health, Lublin, Poland; Department of Pathophysiology, Medical University of Lublin, Poland.
authors.forename: Stanisław J
authors.initials: SJ
authors.lastname: Czuczwar
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects*; D001562:Benzimidazoles / Q000494:pharmacology* / Q000633:toxicity; D001565:Benzoates / Q000494:pharmacology* / Q000633:toxicity; D004195:Disease Models, Animal; D004347:Drug Interactions; D004597:Electroshock; D019808:Losartan / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects*; D009557:Nipecotic Acids / Q000494:pharmacology* / Q000633:toxicity; D019338:Polypharmacy; D011597:Psychomotor Performance / Q000187:drug effects*; D012640:Seizures / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control* / Q000523:psychology; D000077333:Telmisartan; D000078308:Tiagabine; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000927:Anticonvulsants; D001562:Benzimidazoles; D001565:Benzoates; D009557:Nipecotic Acids; D019808:Losartan; D000077333:Telmisartan; D000078308:Tiagabine