RESEARCH PAPER
Assessment of combined treatment with vigabatrin and antihypertensive drugs against electroconvulsions in mice
1
Department of Physiopathology, Institute of Rural Health, Lublin, Poland
2
Department of Pathophysiology, Medical University of Lublin, Lublin, Poland
Corresponding author
Krzysztof Łukawski
Department of Physiopathology, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland
Department of Physiopathology, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland
J Pre Clin Clin Res. 2015;9(1):1-4
KEYWORDS
ABSTRACT
Introduction and objective:
It is likely that cardiovascular drugs will be used in epileptic patients because heart failure and hypertension are common comorbid conditions with epilepsy. Experimental studies show that some cardiovascular drugs can affect the protective activity of antiepileptics. The aim of this study was to examine the effects in mice of angiotensin-converting enzyme (ACE) inhibitors (captopril and perindopril), angiotensin AT1 receptor antagonists (losartan and candesartan) and diuretics (hydrochlorothiazide and ethacrynic acid) on the anticonvulsant activity of vigabatrin (VGB), a second generation antiepileptic drug.
Material and Methods:
Adult Swiss mice were used in the study. The anticonvulsant action of VGB was assessed in the maximal electroshock seizure threshold test. Combined treatment with VGB and antihypertensive drugs was also tested for adverse effects in the passive avoidance task and chimney test. All drugs were administered intraperitoneally.
Results:
Captopril (50 mg/kg), perindopril (10 mg/kg), losartan (50 mg/kg), candesartan (8 mg/kg), hydrochlorothiazide (100 mg/kg) and ethacrynic acid (100 mg/kg) did not influence the protective action of VGB. The combined treatment with VGB (700 mg/kg) and antihypertensive drugs showed a strong tendency towards impaired retention in the passive avoidance task, and in the case of the combination of VGB with ethacrynic acid it reached statistical significance (P < 0.05). Mice were not disturbed in the chimney test following applied treatment.
Conclusions:
From the preclinical point of view, the use of the tested antihypertensive drugs in patients treated with VGB seems neutral regarding its anticonvulsant activity.
It is likely that cardiovascular drugs will be used in epileptic patients because heart failure and hypertension are common comorbid conditions with epilepsy. Experimental studies show that some cardiovascular drugs can affect the protective activity of antiepileptics. The aim of this study was to examine the effects in mice of angiotensin-converting enzyme (ACE) inhibitors (captopril and perindopril), angiotensin AT1 receptor antagonists (losartan and candesartan) and diuretics (hydrochlorothiazide and ethacrynic acid) on the anticonvulsant activity of vigabatrin (VGB), a second generation antiepileptic drug.
Material and Methods:
Adult Swiss mice were used in the study. The anticonvulsant action of VGB was assessed in the maximal electroshock seizure threshold test. Combined treatment with VGB and antihypertensive drugs was also tested for adverse effects in the passive avoidance task and chimney test. All drugs were administered intraperitoneally.
Results:
Captopril (50 mg/kg), perindopril (10 mg/kg), losartan (50 mg/kg), candesartan (8 mg/kg), hydrochlorothiazide (100 mg/kg) and ethacrynic acid (100 mg/kg) did not influence the protective action of VGB. The combined treatment with VGB (700 mg/kg) and antihypertensive drugs showed a strong tendency towards impaired retention in the passive avoidance task, and in the case of the combination of VGB with ethacrynic acid it reached statistical significance (P < 0.05). Mice were not disturbed in the chimney test following applied treatment.
Conclusions:
From the preclinical point of view, the use of the tested antihypertensive drugs in patients treated with VGB seems neutral regarding its anticonvulsant activity.
REFERENCES (28)
1.
Faught E. Vigabatrin therapy for refractory complex partial seizures: review of clinical trial experience in the United States. Acta Neurol Scand Suppl. 2011; (192): 29–35.
2.
Lasoń W, Dudra-Jastrzębska M, Rejdak K, Czuczwar SJ. Basic mechanisms of antiepileptic drugs and their pharmacokinetic/ pharmacodynamic interactions: an update. Pharmacol Rep. 2011; 63(2): 271–292.
3.
Gaitatzis A, Carroll K, Majeed A, Sander JW. The epidemiology of the comorbidity of epilepsy in the general population. Epilepsia 2004; 45(12): 1613–1622.
4.
Łukawski K, Janowska A, Jakubus T, Tochman-Gawda A, Czuczwar SJ. Angiotensin AT1 receptor antagonists enhance the anticonvulsant action of valproate in the mouse model of maximal electroshock. Eur J Pharmacol. 2010; 640(1–3): 172–177.
5.
Łukawski K, Jakubus T, Raszewski G, Czuczwar SJ. Captopril potentiates the anticonvulsant activity of carbamazepine and lamotrigine in the mouse maximal electroshock seizure model. J Neural Transm. 2010; 117(10): 1161–1166.
6.
Łuszczki JJ, Ratnaraj N, Patsalos PN, Czuczwar SJ. Isobolographic and behavioral characterizations of interactions between vigabatrin and gabapentin in two experimental models of epilepsy. Eur J Pharmacol. 2008; 595(1–3): 13–21.
7.
Molnar J, Somberg JC. The clinical pharmacology of ethacrynic acid. Am J Ther. 2009; 16(1): 86–92.
8.
Reid KH, Guo SZ, Iyer VG. Agents which block potassium-chloride cotransport prevent sound-triggered seizures in post-ischemic audiogenic seizure-prone rats. Brain Res. 2000; 864(1): 134–137.
9.
Łukawski K, Świderska G, Łuszczki JJ, Czuczwar SJ. Influence of ethacrynic acid on the anticonvulsant activity of conventional antiepileptic drugs in the mouse maximal electroshock seizure model. Pharmacol Rep. 2010; 62(5): 808–813.
10.
Łukawski K, Świderska G, Czuczwar SJ. Effect of hydrochlorothiazide on the anticonvulsant action of antiepileptic drugs against maximal electroshock-induced seizures in mice. Pharmacol Rep. 2012; 64(2): 315–320.
11.
De Sarro G, Paola ED, Gratteri S, Gareri P, Rispoli V, Siniscalchi A, Tripepi G, GallelliL, Citraro R, Russo E. Fosinopril and zofenopril, two angiotensin-converting enzyme (ACE) inhibitors, potentiate the anticonvulsant activity of antiepileptic drugs against audiogenic seizures in DBA/2 mice. Pharmacol Res. 2012; 65(3): 285–296.
12.
Venault P, Chapouthier G, Prado de Carvalho L, Simiand J, Morre M, Dodd RH, Rossier J. Benzodiazepine impairs and β-carboline enhances performance in learning and memory tasks. Nature1986; 321(6073): 864–866.
13.
Boissier JR, Tardy J, Diverres JC. Une nouvelle methode simple pour explorer l’action ‘tranquilisante’: le test de la cheminee. Med Exp. 1960; 3(1): 81–84.
14.
Litchfield JT, Wilcoxon F. A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther. 1949; 96(2): 99–113.
15.
Łuszczki JJ, Czuczwar SJ. How significant is the difference between drug doses influencing the threshold for electroconvulsions? Pharmacol Rep. 2005; 57(6): 782–786.
16.
Czapiński P, Blaszczyk B, Czuczwar SJ. Mechanisms of action of antiepileptic drugs. Curr Top Med Chem. 2005; 5(1): 3–14.
17.
Engelborghs S, Pickut BA, D’Hooge R, Wiechert P, Haegele K, De Deyn PP. Behavioral effects of vigabatrin correlated with whole brain gamma-aminobutyric acid metabolism in audiogenic sensitive rats. Arzneimittelforschung 1998; 48(7): 713–716.
18.
Mecarelli O, De Feo MR, Del Priore D. Vigabatrin versus carbamazepine and phenytoin in kainic acid-treated pubescent rats. Pharmacol Res. 1997; 36(2): 87–93.
19.
Pitkänen A, Tuunanen J, Halonen T. Vigabatrin and carbamazepine have different efficacies in the prevention of status epilepticus induced neuronal damage in the hippocampus and amygdala. Epilepsy Res. 1996; 24(1): 29–45.
20.
Georgiev VP, Lazarova MB, Kambourova TS. Effects of non-peptide angiotensin II-receptor antagonists on pentylenetetrazol kindling in mice. Neuropeptides 1996; 30(5): 401–404.
21.
Margineanu DG, Klitgaard H. Differential effects of cation-chloride co-transport-blocking diuretics in a rat hippocampal slice model of epilepsy. Epilepsy Res. 2006; 69(2): 93–99.
22.
Deckers CL, Czuczwar SJ, Hekster YA, Keyser A, Kubova H, Meinardi H, Patsalos PN, Renier WO, Van Rijn CM. Selection of antiepileptic drug polytherapy based on mechanisms of action: the evidence reviewed. Epilepsia 2000; 41(11): 1364–1374.
23.
Łuszczki JJ, Wojcik-Cwikla J, Andres MM, Czuczwar SJ. Pharmacological and behavioral characteristics of interactions between vigabatrin and conventional antiepileptic drugs in pentylenetetrazole-induced seizures in mice: an isobolographic analysis. Neuropsychopharmacology 2005; 30(5): 958–973.
24.
Mazurkiewicz M, Sirviö J, Riekkinen P Sr. Effects of single and repeated administration of vigabatrin on the performance of non-epileptic rats in a delayed non-matching to position task. Epilepsy Res. 1993; 15(3): 221–227.
25.
Celikyurt IK, Mutlu O, Ulak G, Akar FY, Erden F. Gabapentin, A GABA analogue, enhances cognitive performance in mice. Neurosci Lett. 2011; 492(2): 124–128.
26.
Zarrindast MR, Bakhsha A, Rostami P, Shafaghi B. Effects of intrahippocampal injection of GABAergic drugs on memory retention of passive avoidance learning in rats. J Psychopharmacol. 2002; 16(4): 313–319.
27.
Jasmin L, Rabkin SD, Granato A, Boudah A, Ohara PT. Analgesia and hyperalgesia from GABA-mediated modulation of the cerebral cortex. Nature 2003; 424(6946): 316–320.
28.
Czuczwar M, Kiś J, Potasiński A, Turski WA, Przesmycki K. Isobolographic analysis of interaction between vigabatrin and baclofen in the formalin test in mice. Pol J Pharmacol. 2001; 53(5): 527–530.
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