Document Detail


Interaction of the anticonvulsant ameltolide with standard anticonvulsants.
MedLine Citation:
PMID:  1628588     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The newly characterized anticonvulsant ameltolide was studied in mice in combination with the standard antiepileptic drugs (AEDs), phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA). In combination with either PHT or CBZ, ameltolide produced dose-additive effects in the maximal electroshock (MES) test and in the horizontal screen (HS) test for neurologic impairment. The large separation between the doses for the anticonvulsant effects and the neurologically impairing effects (protective index, PI) were maintained as well in the combinations as in the individual compounds. VPA was impotent in the MES test and did not have a clear separation between the doses that produce the anticonvulsant effects and those that are neurologically impairing (low PI). When VPA and ameltolide were combined, the effects were less than additive by isobolographic analysis on both the MES and HS tests. At high oral doses (20 and 40 mg/kg, p.o.), ameltolide produced impairment on the HS test and decreased body temperature. The effects on the HS test were enhanced twofold, whereas the effects on body temperature were not markedly enhanced, by coadministration of the MES ED95 of PHT and CBZ. VPA (MES ED95) appeared to antagonize the temperature-lowering effects of ameltolide. These interaction studies suggest that ameltolide would be safe, with no unexpected effects, when used in epileptic patients concurrently receiving these standard AEDs. These studies also suggest that the effects of ameltolide would be lessened by simultaneous administration of VPA.
Authors:
J D Leander
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Epilepsia     Volume:  33     ISSN:  0013-9580     ISO Abbreviation:  Epilepsia     Publication Date:    1992 Jul-Aug
Date Detail:
Created Date:  1992-08-17     Completed Date:  1992-08-17     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  2983306R     Medline TA:  Epilepsia     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  705-11     Citation Subset:  IM    
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anticonvulsants / pharmacology*,  therapeutic use
Benzamides / pharmacology*,  therapeutic use
Carbamazepine / pharmacology
Dose-Response Relationship, Drug
Drug Interactions
Drug Therapy, Combination
Electroshock
Epilepsy / drug therapy
Humans
Male
Mice
Motor Activity / drug effects
Phenytoin / pharmacology
Seizures / etiology,  prevention & control
Valproic Acid / pharmacology
Chemical
Reg. No./Substance:
0/Anticonvulsants; 0/Benzamides; 298-46-4/Carbamazepine; 57-41-0/Phenytoin; 787-93-9/ameltolide; 99-66-1/Valproic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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