title: Enalapril enhances the anticonvulsant activity of lamotrigine in the test of maximal electroshock.
abstract: BACKGROUND
  The aim of this study was to find out whether angiotensin-converting enzyme (ACE) inhibitors, enalapril and cilazapril, affect the anticonvulsant action of some second-generation antiepileptics, lamotrigine (LTG), topiramate (TPM) and oxcarbazepine (OXC).
  
  
  METHODS
  The effects of ACE inhibitors on antiepileptic drugs were examined in the mouse model of maximal electroshock.
  
  
  RESULTS
  Enalapril (30 mg/kg ip) potentiated the anticonvulsant action of LTG, decreasing its ED50 value from 5.3 to 3.6 mg/kg (p < 0.01). The anticonvulsant activity of TPM or OXC was not modified by enalapril. Cilazapril did not affect the protective activity of the studied antiepileptics. The interaction between enalapril and LTG could be pharmacodynamic in nature because enalapril did not change plasma and total brain concentrations of LTG.
  
  
  CONCLUSIONS
  This study shows that there are no negative interactions between the studied antiepileptic drugs and enalapril or cilazapril. Enalapril even enhanced the anticonvulsant activity of LTG in the MES test in mice that is thought to be a predictive model of human generalized tonic-clonic seizures.
authors.affiliation: Department of Physiopathology, Institute of Agricultural Medicine, Jaczewskiego 2, PL 20-090 Lublin, Poland. lukaw@mp.pl.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Łukawski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Jakubus
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Janowska
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Raszewski
authors.forename: Stanisław J
authors.initials: SJ
authors.lastname: Czuczwar
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D017315:Cilazapril / Q000494:pharmacology; D004357:Drug Synergism; D004597:Electroshock; D004656:Enalapril / Q000494:pharmacology*; D005632:Fructose / Q000031:analogs & derivatives / Q000494:pharmacology; D000077213:Lamotrigine; D008297:Male; D051379:Mice; D000078330:Oxcarbazepine; D011597:Psychomotor Performance / Q000187:drug effects; D000077236:Topiramate; D014227:Triazines / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000927:Anticonvulsants; D014227:Triazines; D000077236:Topiramate; D017315:Cilazapril; D005632:Fructose; D002220:Carbamazepine; D004656:Enalapril; D000077213:Lamotrigine; D000078330:Oxcarbazepine