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Interactions between non-barbiturate injectable anesthetics and conventional antiepileptic drugs in the maximal electroshock test in mice--an isobolographic analysis.
Eur Neuropsychopharmacol. 2004 Mar; 14(2):163-72.EN

Abstract

The aim of this study was the isobolographic evaluation of interactions between three non-barbiturate intravenous anesthetics and conventional antiepileptic drugs in the maximal electroshock-induced seizures in mice. Electroconvulsions were produced by means of an alternating current (ear-clip electrodes, 0.2-s stimulus duration, tonic hindlimb extension taken as the endpoint). Adverse effects were evaluated in the chimney test (motor performance) and passive avoidance task (long-term memory). Plasma levels of antiepileptic drugs were measured by immunofluorescence. Obtained results indicate that ketamine acts synergistically with valproate and carbamazepine. Also the combinations of propofol and valproate or phenobarbital led to synergistic interactions. An antagonism was found between etomidate and carbamazepine or phenobarbital. On the other hand, interactions between diphenylhydantoin and injectable anesthetics proved to be additive. The only exception was the combination of diphenylhydantoin and propofol (1:3). Pharmacokinetic phenomena do not seem to interfere with the observed interactions, since none of anesthetics influenced the free plasma concentrations of antiepileptic drugs. Referring to undesired effects, only propofol impaired long-term memory. Although propofol did not disturbed motor coordination, it enhanced motor impairment caused by carbamazepine and diphenylhydantoin. Results of the present study suggest that etomidate needs to be avoided in epileptic patients due to a possibility of negative interactions with some antiepileptic drugs and seizure precipitation.

Authors+Show Affiliations

Department of Pathophysiology, Medical University, 20-090 Lublin, Jaczewskiego 8, Poland.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15013033

Citation

Borowicz, Kinga K., et al. "Interactions Between Non-barbiturate Injectable Anesthetics and Conventional Antiepileptic Drugs in the Maximal Electroshock Test in Mice--an Isobolographic Analysis." European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, vol. 14, no. 2, 2004, pp. 163-72.
Borowicz KK, Łuszczki J, Czuczwar SJ. Interactions between non-barbiturate injectable anesthetics and conventional antiepileptic drugs in the maximal electroshock test in mice--an isobolographic analysis. Eur Neuropsychopharmacol. 2004;14(2):163-72.
Borowicz, K. K., Łuszczki, J., & Czuczwar, S. J. (2004). Interactions between non-barbiturate injectable anesthetics and conventional antiepileptic drugs in the maximal electroshock test in mice--an isobolographic analysis. European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, 14(2), 163-72.
Borowicz KK, Łuszczki J, Czuczwar SJ. Interactions Between Non-barbiturate Injectable Anesthetics and Conventional Antiepileptic Drugs in the Maximal Electroshock Test in Mice--an Isobolographic Analysis. Eur Neuropsychopharmacol. 2004;14(2):163-72. PubMed PMID: 15013033.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interactions between non-barbiturate injectable anesthetics and conventional antiepileptic drugs in the maximal electroshock test in mice--an isobolographic analysis. AU - Borowicz,Kinga K, AU - Łuszczki,Jarogniew, AU - Czuczwar,Stanisław J, PY - 2003/03/25/received PY - 2003/06/17/revised PY - 2003/07/08/accepted PY - 2004/3/12/pubmed PY - 2004/4/20/medline PY - 2004/3/12/entrez SP - 163 EP - 72 JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JO - Eur Neuropsychopharmacol VL - 14 IS - 2 N2 - The aim of this study was the isobolographic evaluation of interactions between three non-barbiturate intravenous anesthetics and conventional antiepileptic drugs in the maximal electroshock-induced seizures in mice. Electroconvulsions were produced by means of an alternating current (ear-clip electrodes, 0.2-s stimulus duration, tonic hindlimb extension taken as the endpoint). Adverse effects were evaluated in the chimney test (motor performance) and passive avoidance task (long-term memory). Plasma levels of antiepileptic drugs were measured by immunofluorescence. Obtained results indicate that ketamine acts synergistically with valproate and carbamazepine. Also the combinations of propofol and valproate or phenobarbital led to synergistic interactions. An antagonism was found between etomidate and carbamazepine or phenobarbital. On the other hand, interactions between diphenylhydantoin and injectable anesthetics proved to be additive. The only exception was the combination of diphenylhydantoin and propofol (1:3). Pharmacokinetic phenomena do not seem to interfere with the observed interactions, since none of anesthetics influenced the free plasma concentrations of antiepileptic drugs. Referring to undesired effects, only propofol impaired long-term memory. Although propofol did not disturbed motor coordination, it enhanced motor impairment caused by carbamazepine and diphenylhydantoin. Results of the present study suggest that etomidate needs to be avoided in epileptic patients due to a possibility of negative interactions with some antiepileptic drugs and seizure precipitation. SN - 0924-977X UR - https://www.unboundmedicine.com/medline/citation/15013033/Interactions_between_non_barbiturate_injectable_anesthetics_and_conventional_antiepileptic_drugs_in_the_maximal_electroshock_test_in_mice__an_isobolographic_analysis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924977X03001044 DB - PRIME DP - Unbound Medicine ER -