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Interactions between two enantiomers of losigamone and conventional antiepileptic drugs in the mouse maximal electroshock model--an isobolographic analysis.
Eur J Pharmacol. 2007 Jul 12; 567(1-2):110-6.EJ

Abstract

The aim of this study was the isobolographic evaluation of interactions between two enantiomers of losigamone, AO-242 [(+)-5(R)-alpha(S)-5-(2-chlorophenylhydroxymethyl)-4-methoxy-2(5H)-furanone] and AO-294 [(-)-5(S)-alpha(R)-5-(2-chlorophenylhydroxymethyl)-4-methoxy-2(5H)-furanone], and valproate, carbamazepine, phenytoin, or phenobarbital in the maximal electroshock test in mice. Both enantiomers interacted additively with conventional antiepileptic drugs at all studied fixed dose ratios (1:3, 1:1, 3:1). Furthermore, AO-242, AO-294 and antiepileptics applied alone, as well as combinations of enantiomers and antiepileptics did not affect motor performance in the chimney test. Significant impairment of long-term memory (passive-avoidance task) was noted only in the case of valproate alone, given at the dose equal to its median effective dose (ED(50)) against maximal electroshock. All other antiepileptics and their combinations with AO-242 or AO-294 did not impair memory of mice. Enantiomers did not affect the brain concentrations of antiepileptic drugs, indicating a pharmacodynamic nature of the observed interactions. In conclusion, the present results suggest both AO-242 and AO-294 as promising candidate drugs in the add-on therapy of refractory epilepsy.

Authors+Show Affiliations

Department of Pathophysiology, Medical University, Lublin, Poland. kinga.borowicz@am.lublin.plNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

17482161

Citation

Borowicz, Kinga K., et al. "Interactions Between Two Enantiomers of Losigamone and Conventional Antiepileptic Drugs in the Mouse Maximal Electroshock Model--an Isobolographic Analysis." European Journal of Pharmacology, vol. 567, no. 1-2, 2007, pp. 110-6.
Borowicz KK, Jaszczyk B, Luszczki JJ, et al. Interactions between two enantiomers of losigamone and conventional antiepileptic drugs in the mouse maximal electroshock model--an isobolographic analysis. Eur J Pharmacol. 2007;567(1-2):110-6.
Borowicz, K. K., Jaszczyk, B., Luszczki, J. J., & Czuczwar, S. J. (2007). Interactions between two enantiomers of losigamone and conventional antiepileptic drugs in the mouse maximal electroshock model--an isobolographic analysis. European Journal of Pharmacology, 567(1-2), 110-6.
Borowicz KK, et al. Interactions Between Two Enantiomers of Losigamone and Conventional Antiepileptic Drugs in the Mouse Maximal Electroshock Model--an Isobolographic Analysis. Eur J Pharmacol. 2007 Jul 12;567(1-2):110-6. PubMed PMID: 17482161.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interactions between two enantiomers of losigamone and conventional antiepileptic drugs in the mouse maximal electroshock model--an isobolographic analysis. AU - Borowicz,Kinga K, AU - Jaszczyk,Bozena, AU - Luszczki,Jarogniew J, AU - Czuczwar,Stanislaw J, Y1 - 2007/04/14/ PY - 2006/12/13/received PY - 2007/03/28/revised PY - 2007/04/01/accepted PY - 2007/5/8/pubmed PY - 2007/7/28/medline PY - 2007/5/8/entrez SP - 110 EP - 6 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 567 IS - 1-2 N2 - The aim of this study was the isobolographic evaluation of interactions between two enantiomers of losigamone, AO-242 [(+)-5(R)-alpha(S)-5-(2-chlorophenylhydroxymethyl)-4-methoxy-2(5H)-furanone] and AO-294 [(-)-5(S)-alpha(R)-5-(2-chlorophenylhydroxymethyl)-4-methoxy-2(5H)-furanone], and valproate, carbamazepine, phenytoin, or phenobarbital in the maximal electroshock test in mice. Both enantiomers interacted additively with conventional antiepileptic drugs at all studied fixed dose ratios (1:3, 1:1, 3:1). Furthermore, AO-242, AO-294 and antiepileptics applied alone, as well as combinations of enantiomers and antiepileptics did not affect motor performance in the chimney test. Significant impairment of long-term memory (passive-avoidance task) was noted only in the case of valproate alone, given at the dose equal to its median effective dose (ED(50)) against maximal electroshock. All other antiepileptics and their combinations with AO-242 or AO-294 did not impair memory of mice. Enantiomers did not affect the brain concentrations of antiepileptic drugs, indicating a pharmacodynamic nature of the observed interactions. In conclusion, the present results suggest both AO-242 and AO-294 as promising candidate drugs in the add-on therapy of refractory epilepsy. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17482161/Interactions_between_two_enantiomers_of_losigamone_and_conventional_antiepileptic_drugs_in_the_mouse_maximal_electroshock_model__an_isobolographic_analysis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)00433-5 DB - PRIME DP - Unbound Medicine ER -