Effects of progabide on bicuculline-induced epileptic seizures in developing rats.
The effects of progabide, a direct gamma-aminobutyric acid (GABA) receptor agonist, on bicuculline-induced seizures have been tested in developing rats, ages 7-28 days, to study the correlation between the antiepileptic effectiveness of this drug and the level of functional maturation of the GABAergic system. The incidence, latency of appearance, and behavioral characteristics of the epileptic manifestations, their evolution toward status epilepticus, and the percentage of recovery from status epilepticus have been evaluated in rats that had received a single injection (treatment) or three successive daily administrations (pretreatment) of progabide. The results have been compared with those obtained in a control group of animals in which only bicuculline had been injected. In rats ages 7-14 days the treatment appears to be substantially ineffective in protecting animals against bicuculline seizures and their consequences, probably because of the substantial immaturity of the GABAergic system at birth and during the first days of life. At this age, repetitive administrations of progabide cause a protective anticonvulsant action more remarkable than the single injection, particularly when using the higher doses of the substance. In 15-28-day-old rats, the treatment significantly reduces the lethality from status epilepticus but does not substantially modify the incidence of seizures, their latency of appearance, or their evolution toward status epilepticus. As in younger animals, in these rats also pretreatment is more effective than treatment against bicuculline seizures, whatever dose of progabide is used. At this age, therefore, the anticonvulsant properties of progabide appear to be more remarkable than in the previous age, probably because of a higher level of development of the GABAergic system, according to biochemical data on the GABAergic system ontogenesis.
Mecarelli
O
O
Dipartimento di Scienze Neurologiche, Università La Sapienza, Rome, Italy.
de Feo
M R
MR
Rina
M F
MF
Ricci
G F
GF
D000375:Aging; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001640:Bicuculline; D005260:Female; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D013226:Status Epilepticus / Q000188:drug therapy / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000927:Anticonvulsants; C017985:progabide; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline