Effect of hydrochlorothiazide on the anticonvulsant action of antiepileptic drugs against maximal electroshock-induced seizures in mice.
BACKGROUND
The purpose of this study was to evaluate the effect of hydrochlorothiazide (HCTZ), a thiazide-type diuretic and an antihypertensive drug, on the anticonvulsant activity of numerous antiepileptic drugs (AEDs: carbamazepine--CBZ, phenytoin--PHT, valproate--VPA, phenobarbital--PB, oxcarbazepine--OXC, lamotrigine--LTG and topiramate--TPM).


METHODS
The effects of HCTZ and AEDs on convulsions were examined in the maximal electroshock seizure (MES) test in mice. Additionally, adverse effects of combined treatment with HCTZ and the AEDs in the passive avoidance task and chimney test were assessed. All drugs were injected intraperitoneally (ip) at single doses.


RESULTS
The data obtained indicate that HCTZ (100 mg ip) enhanced the anticonvulsant action of CBZ, decreasing its ED(50) value from 11.9 to 7.7 mg/kg (p < 0.05), and had no impact on the antielectroshock activity of the other AEDs. The observed interaction between HCTZ and CBZ was not pharmacokinetic in nature as HCTZ did not alter free plasma (non-protein-bound) and total brain concentrations of CBZ. The combined treatment with HCTZ and the AEDs was free from side-effects on motor performance and long-term memory in mice.


CONCLUSIONS
To the degree, the experimental data can be transferred to clinical conditions, the use of a single dose of HCTZ in patients receiving VPA, PHT, PB, OXC, LTG or TPM, seems neutral regarding their anticonvulsant potency. Acute HCTZ may positively influence the anticonvulsant action of CBZ in epileptic patients.
Department of Physiopathology, Institute of Agricultural Medicine, Jaczewskiego 2, PL 20-090 Lublin, Poland. lukaw@mp.pl
Krzysztof
K
Łukawski
Grażyna
G
Swiderska
Stanisław J
SJ
Czuczwar
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004597:Electroshock; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology; D014018:Tissue Distribution
D000927:Anticonvulsants; D006852:Hydrochlorothiazide