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Indapamide enhances the protective action of carbamazepine, phenobarbital, and valproate against maximal electroshock-induced seizures in mice.
Adv Med Sci. 2009; 54(1):66-74.AM

Abstract

PURPOSE

To determine the influence of indapamide on the protective action of numerous conventional and second-generation antiepileptic drugs (carbamazepine, lamotrigine, oxcarbazepine, phenobarbital, topiramate and valproate) in the mouse maximal electroshock seizure model.

MATERIAL AND METHODS

Electroconvulsions were evoked in Albino Swiss mice by a current (sine-wave, 0.2 s stimulus duration) delivered via auricular electrodes. Adverse-effect profiles with respect to motor performance, long-term memory and skeletal muscular strength were measured along with total brain antiepileptic drug concentrations.

RESULTS

Indapamide (up to 3 mg/kg, i.p., 120 min before the test) neither altered the threshold for maximal electroconvulsions, nor protected the animals against maximal electroshock-induced seizures in mice. Moreover, indapamide (3 mg/kg, i.p.) significantly enhanced the anticonvulsant action of carbamazepine, phenobarbital and valproate, but not that of lamotrigine, oxcarbazepine or topiramate in the maximal electroshock seizure test in mice. Indapamide (1.5 mg/kg) had no impact on the anticonvulsant action of all studied antiepileptic drugs in the maximal electroshock seizure test in mice. Estimation of total brain antiepileptic drug concentrations revealed that the observed interaction between indapamide and phenobarbital was complicated by a significant pharmacokinetic increase in total brain concentrations of phenobarbital. In contrast, indapamide had no impact on the total brain concentrations of carbamazepine and valproate in mice.

CONCLUSIONS

The selective potentiation of the anticonvulsant action of carbamazepine and valproate by indapamide and lack of any pharmacokinetic interactions between drugs, make the combinations of indapamide with carbamazepine or valproate of pivotal importance for epileptic patients taking these drugs together.

Authors+Show Affiliations

Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19366652

Citation

Kozinska, J, et al. "Indapamide Enhances the Protective Action of Carbamazepine, Phenobarbital, and Valproate Against Maximal Electroshock-induced Seizures in Mice." Advances in Medical Sciences, vol. 54, no. 1, 2009, pp. 66-74.
Kozinska J, Sawicka KM, Zadrozniak A, et al. Indapamide enhances the protective action of carbamazepine, phenobarbital, and valproate against maximal electroshock-induced seizures in mice. Adv Med Sci. 2009;54(1):66-74.
Kozinska, J., Sawicka, K. M., Zadrozniak, A., Wojda, E., Andres-Mach, M., Dudra-Jastrzebska, M., & Luszczki, J. J. (2009). Indapamide enhances the protective action of carbamazepine, phenobarbital, and valproate against maximal electroshock-induced seizures in mice. Advances in Medical Sciences, 54(1), 66-74. https://doi.org/10.2478/v10039-009-0004-9
Kozinska J, et al. Indapamide Enhances the Protective Action of Carbamazepine, Phenobarbital, and Valproate Against Maximal Electroshock-induced Seizures in Mice. Adv Med Sci. 2009;54(1):66-74. PubMed PMID: 19366652.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Indapamide enhances the protective action of carbamazepine, phenobarbital, and valproate against maximal electroshock-induced seizures in mice. AU - Kozinska,J, AU - Sawicka,K M, AU - Zadrozniak,A, AU - Wojda,E, AU - Andres-Mach,M, AU - Dudra-Jastrzebska,M, AU - Luszczki,J J, PY - 2009/4/16/entrez PY - 2009/4/16/pubmed PY - 2010/1/28/medline SP - 66 EP - 74 JF - Advances in medical sciences JO - Adv Med Sci VL - 54 IS - 1 N2 - PURPOSE: To determine the influence of indapamide on the protective action of numerous conventional and second-generation antiepileptic drugs (carbamazepine, lamotrigine, oxcarbazepine, phenobarbital, topiramate and valproate) in the mouse maximal electroshock seizure model. MATERIAL AND METHODS: Electroconvulsions were evoked in Albino Swiss mice by a current (sine-wave, 0.2 s stimulus duration) delivered via auricular electrodes. Adverse-effect profiles with respect to motor performance, long-term memory and skeletal muscular strength were measured along with total brain antiepileptic drug concentrations. RESULTS: Indapamide (up to 3 mg/kg, i.p., 120 min before the test) neither altered the threshold for maximal electroconvulsions, nor protected the animals against maximal electroshock-induced seizures in mice. Moreover, indapamide (3 mg/kg, i.p.) significantly enhanced the anticonvulsant action of carbamazepine, phenobarbital and valproate, but not that of lamotrigine, oxcarbazepine or topiramate in the maximal electroshock seizure test in mice. Indapamide (1.5 mg/kg) had no impact on the anticonvulsant action of all studied antiepileptic drugs in the maximal electroshock seizure test in mice. Estimation of total brain antiepileptic drug concentrations revealed that the observed interaction between indapamide and phenobarbital was complicated by a significant pharmacokinetic increase in total brain concentrations of phenobarbital. In contrast, indapamide had no impact on the total brain concentrations of carbamazepine and valproate in mice. CONCLUSIONS: The selective potentiation of the anticonvulsant action of carbamazepine and valproate by indapamide and lack of any pharmacokinetic interactions between drugs, make the combinations of indapamide with carbamazepine or valproate of pivotal importance for epileptic patients taking these drugs together. SN - 1898-4002 UR - https://www.unboundmedicine.com/medline/citation/19366652/Indapamide_enhances_the_protective_action_of_carbamazepine_phenobarbital_and_valproate_against_maximal_electroshock_induced_seizures_in_mice_ L2 - https://medlineplus.gov/seizures.html DB - PRIME DP - Unbound Medicine ER -