Gabapentin potentiates the antiseizure activity of certain anticonvulsants in DBA/2 mice.
Gabapentin (1-50 mg/kg, intraperitoneally (i.p.)) was able to antagonize audiogenic seizures in Dilute Brown Agouti DBA2J (DBA/2) mice in a dose-dependent manner. Gabapentin at dose of 2.5 mg/kg i.p., which per se did not significantly affect the occurrence of audiogenic seizures in DBA/2 mice, potentiated the anticonvulsant activity of carbamazepine, diazepam, felbamate, lamotrigine, phenytoin, phenobarbital and valproate against sound-induced seizures in DBA/2 mice. The potentiation induced by gabapentin was greatest for diazepam, phenobarbital and valproate, less for felbamate and phenytoin and least for carbamazepine and lamotrigine. The increase in anticonvulsant activity was associated with a comparable increase in motor impairment. However, the therapeutic index of combined treatment of the above drugs + gabapentin was more favourable than that of the same drugs + saline. Since gabapentin did not significantly influence the total and free plasma levels of the anticonvulsant drugs studied, we suggest that pharmacokinetic interactions, in terms of total or free plasma levels, are not probable. However, the possibility that gabapentin can modify the clearance from the brain of the anticonvulsant drugs studied can not be excluded. In addition, gabapentin did not significantly affect the hypothermic effects of the anticonvulsants tested. In conclusion, gabapentin showed an additive effect when administered in combination with certain classical anticonvulsants, most notably diazepam, phenobarbital, felbamate, phenytoin and valproate.
Department of Experimental and Clinical Medicine, Faculty of Medicine and Surgery, University of Catanzaro, Policlinico Mater Domini, Italy.
G
G
De Sarro
C
C
Spagnolo
P
P
Gareri
L
L
Gallelli
A
A
De Sarro
D000085:Acetates / Q000627:therapeutic use*; D000161:Acoustic Stimulation; D000588:Amines; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D003509:Cyclohexanecarboxylic Acids; D004357:Drug Synergism; D005260:Female; D000077206:Gabapentin; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D012640:Seizures / Q000188:drug therapy*; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin