title: Combined treatment with gabapentin and drugs affecting the renin-angiotensin system against electroconvulsions in mice.
abstract: Recent experimental data suggest that certain angiotensin-converting enzyme (ACE) inhibitors and angiotensin AT1 receptor antagonists may possess anticonvulsant activity. The purpose of this study was to examine the effects of two ACE inhibitors, captopril and enalapril, and two AT1 receptor antagonists, losartan and telmisartan, on the protective action of gabapentin in the maximal electroshock seizure threshold test in mice. Additionally, the effects of the combined treatment with gabapentin and antihypertensive drugs on memory retention in the passive avoidance task and motor coordination in the chimney test were assessed. All drugs were injected intraperitoneally. Losartan (50mg/kg) significantly increased the convulsive threshold for gabapentin. The other antihypertensive drugs, captopril (50mg/kg), enalapril (30 mg/kg) and telmisartan (30 mg/kg), did not affect the anticonvulsant activity of gabapentin. The observed interaction between gabapentin and losartan could be pharmacokinetic in nature. Losartan increased plasma and total brain concentrations of gabapentin. In the chimney test, losartan (50mg/kg) administered with gabapentin (50mg/kg) caused motor impairment. In the passive avoidance test, memory retention was not affected by the combined treatment with gabapentin and antihypertensive drugs. It is suggested that the use of captopril, enalapril and telmisartan in epileptic patients receiving gabapentin is presumed neutral upon its anticonvulsant action. The utmost caution is advised when combining losartan and gabapentin in clinical practice due to the appearance of pharmacokinetic interactions between losartan and gabapentin as well as motor impairment evoked by these drugs in mice.
authors.affiliation: Department of Physiopathology, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland. lukaw@mp.pl
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Lukawski
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Janowska
authors.forename: Tomasz
authors.initials: T
authors.lastname: Jakubus
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Raszewski
authors.forename: Stanisław J
authors.initials: SJ
authors.lastname: Czuczwar
mesh_terms: D000588:Amines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D001362:Avoidance Learning / Q000187:drug effects; D001562:Benzimidazoles / Q000008:administration & dosage; D001565:Benzoates / Q000008:administration & dosage; D001921:Brain / Q000378:metabolism; D002216:Captopril / Q000008:administration & dosage; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D004359:Drug Therapy, Combination; D004597:Electroshock; D004656:Enalapril / Q000008:administration & dosage; D000077206:Gabapentin; D019808:Losartan / Q000008:administration & dosage; D008297:Male; D051379:Mice; D009048:Motor Skills / Q000187:drug effects; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology; D000077333:Telmisartan; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D000588:Amines; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000927:Anticonvulsants; D001562:Benzimidazoles; D001565:Benzoates; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D004656:Enalapril; D000077206:Gabapentin; D002216:Captopril; D019808:Losartan; D000077333:Telmisartan