Effects of piracetam alone and in combination with antiepileptic drugs in rodent seizure models.
The nootropic drug piracetam was investigated in various experimental models of epilepsy. Generally, piracetam exhibits no or only moderate anticonvulsant properties against generalized tonic or clonic seizures. However, in many cases it did increase the anticonvulsant effectiveness of conventional antiepileptics, as shown in the maximal electroshock seizure (MES) threshold test, the traditional MES test or in DBA/2 mice. A pharmacokinetic interaction does not seem to be responsible for this effect. In lethargic mice, a model of absence seizures, piracetam significantly decreased the incidence and duration of spike-wave discharges. Furthermore, in the cobalt-induced focal epilepsy model piracetam reduced the number of spikes/min and in the hippocampal stimulation model it increased the anticonvulsant potency of phenobarbital and phenytoin after single and repeated administration. In conclusion, the well tolerated piracetam itself did not show marked anticonvulsant effects in most screening tests, however, its co-medication with antiepileptic drugs improved seizure protection in various models which may bear potential clinical significance.
Fischer
W
W
Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Germany. fisw@medizin.uni-leipzig.de
Kittner
H
H
Regenthal
R
R
Russo
E
E
De Sarro
G
G
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D003035:Cobalt; D004195:Disease Models, Animal; D004338:Drug Combinations; D004357:Drug Synergism; D004597:Electroshock; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D004832:Epilepsy, Absence / Q000188:drug therapy / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000097:blood / Q000494:pharmacology; D010889:Piracetam / Q000494:pharmacology*; D014635:Valproic Acid / Q000097:blood / Q000494:pharmacology
D000927:Anticonvulsants; D004338:Drug Combinations; D018696:Neuroprotective Agents; D003035:Cobalt; D014635:Valproic Acid; D010672:Phenytoin; D010634:Phenobarbital; D010889:Piracetam