Isobolographic analysis of the mechanisms of action of anticonvulsants from a combination effect

The nature of the pharmacodynamic interactions of drugs is influenced by the drugs׳ mechanisms of action. It has been hypothesized that drugs with different mechanisms are likely to interact synergistically, whereas those with similar mechanisms seem to produce additive interactions. In this review,...

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Bibliographic Details
Published in:European journal of pharmacology 2014-10, Vol.741, p.237-246
Main Authors: Matsumura, Nobuko, Nakaki, Toshio
Format: Article
Language:English
Subjects:
Animal model
Animals
Anticonvulsant
Anticonvulsants - administration & dosage
Anticonvulsants - chemistry
Anticonvulsants - metabolism
Binding Sites - physiology
Carbamazepine - administration & dosage
Carbamazepine - chemistry
Carbamazepine - metabolism
Dose-Response Relationship, Drug
Drug combinations
Drug Therapy, Combination
Humans
Piracetam - administration & dosage
Piracetam - chemistry
Piracetam - metabolism
Seizures - drug therapy
Seizures - metabolism
Subthreshold method
Treatment Outcome
Type I isobolographic analysis
Type II isobolographic analysis
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Summary:The nature of the pharmacodynamic interactions of drugs is influenced by the drugs׳ mechanisms of action. It has been hypothesized that drugs with different mechanisms are likely to interact synergistically, whereas those with similar mechanisms seem to produce additive interactions. In this review, we describe an extensive investigation of the published literature on drug combinations of anticonvulsants, the nature of the interaction of which has been evaluated by type I and II isobolographic analyses and the subthreshold method. The molecular targets of antiepileptic drugs (AEDs) include Na+ and Ca2+ channels, GABA type-A receptor, and glutamate receptors such as NMDA and AMPA/kainate receptors. The results of this review indicate that the nature of interactions evaluated by type I isobolographic analyses but not by the two other methods seems to be consistent with the above hypothesis. Type I isobolographic analyses may be used not only for evaluating drug combinations but also for predicting the targets of new drugs.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2014.08.001