Amlodipine enhances the activity of antiepileptic drugs against pentylenetetrazole-induced seizures.
Amlodipine (AML), which belongs to the 1,4-dihydropyridine calcium channel antagonists, possesses pharmacological and pharmacokinetic profile that distinguishes it from other agents of this class. Pentylenetetrazole (PTZ)-induced clonic and tonic convulsions in mice were significantly reduced by administration of AML at 10 mg/kg. At this dose AML remained without influence upon the plasma level of PTZ. The ED50 value of AML against clonic seizures induced by PTZ was 5.4 mg/kg. This calcium channel antagonist (at 2.5 mg/kg) combined with ethosuximide (ETX), valproate magnesium (VPA) or phenobarbital (PB) significantly reduced their ED50 values against clonic phase of PTZ-induced seizures. AML administered alone or in combination with antiepileptic drugs (AEDs) worsened the motor performance of mice in the chimney test. However, these treatments remained without significant influence on the retention time in the passive avoidance test. Plasma levels of antiepileptics remained unchanged in the presence of AML. The results indicate that AML does not seem a good candidate for a combination therapy in epileptic patients because of its adverse potential.
Kamiński
R M
RM
Isotope Laboratory, Institute of Agricultural Medicine, Lublin, Poland.
Mazurek
M
M
Turski
W A
WA
Kleinrok
Z
Z
Czuczwar
S J
SJ
D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D003292:Convulsants; D004357:Drug Synergism; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D012640:Seizures / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D003292:Convulsants; D017311:Amlodipine; D010433:Pentylenetetrazole