Effects of some calcium antagonists upon the activity of common antiepileptic compounds on sound-induced seizures in DBA/2 mice.
1. Flunarizine (2.65 mumol/kg, i.p.) and nimodipine (5.25 mumol/kg, i.p.) potentiated the anticonvulsant properties of phenytoin, phenobarbital and valproate against audiogenic seizures in DBA/2 mice. 2. Diltiazem (5.25 mumol/kg, i.p.) was able to potentiate the antiseizure activity of phenytoin but was not effective against the anticonvulsant action of phenobarbital and valproate. 3. Verapamil (5.25 mumol/kg, i.p.) was unable to potentiate the anticonvulsant properties of all antiepileptic drugs studied. 4. Bay K 8644 (1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluorophenyl)-pyridine- 5-carboxylic acid), a calcium agonist at a dose of 2.65 mumol/kg, i.p., induced a reduction of anticonvulsant potency of phenytoin, phenobarbital and valproate. 5. None of the calcium antagonists used significantly increased the plasma levels of antiepileptic compounds or significantly affected the body temperature changes induced by anticonvulsant drugs. 6. It may be concluded that some calcium antagonists enhance the anticonvulsant properties of some antiepileptic drugs against audiogenic seizures. A pharmacokinetic interaction does not seem responsible for these effects.
De Sarro
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GB
Institute of Pharmacology, Faculty of Medicine, University of Reggio Calabria, Catanzaro, Italy.
De Sarro
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A
Trimarchi
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GR
Nistico'
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G
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001831:Body Temperature / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004357:Drug Synergism; D005444:Flunarizine / Q000494:pharmacology; D051379:Mice; D008811:Mice, Inbred DBA; D009553:Nimodipine / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology / Q000627:therapeutic use; D010672:Phenytoin / Q000494:pharmacology / Q000627:therapeutic use; D012640:Seizures / Q000188:drug therapy*; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use; D014700:Verapamil / Q000494:pharmacology
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D009553:Nimodipine; D014635:Valproic Acid; D010672:Phenytoin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D004110:Diltiazem; D005444:Flunarizine; D010634:Phenobarbital