The neurotoxicity of phenobarbital and its effect in preventing pentylenetetrazole-induced maximal seizure in aging mice.
The effects of age on the neurotoxicity of phenobarbital and its anticonvulsant effect were examined in female BDF1 mice of different ages by means of a rotorod test and the pentylenetetrazole (PTZ)-induced maximal seizure, respectively. The minimal neurotoxic concentrations (MTCs) of phenobarbital in both plasma and brain evaluated by a rotorod test were 50% lower (p less than 0.05) in old (24-months-old) mice compared with the respective values in young (6-months-old) mice, while 12-months values were the highest of the three groups. Mice given some dosages of phenobarbital, particularly old (24-months-old) mice, died within the 15-min observation period after an i.p. injection of PTZ (150 mg/kg) without demonstrating a hindlimb extensor component (HLE) of maximal seizure. When these animals were classified as responders with regard to the anticonvulsant effect of phenobarbital, the minimal effective concentrations (MECs) in plasma and brain required for abolishing the PTZ-induced maximal seizure in old mice were only 10-20% those of young mice. Present results coupled with our past studies using electroshock seizure suggest that both the neurotoxicity and the efficacy of phenobarbital increase with age in mice.
Kitani
K
K
First Laboratory of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, Japan.
Sato
Y
Y
Kanai
S
S
Ohta
M
M
Nokubo
M
M
Masuda
Y
Y
D000284:Administration, Oral; D000375:Aging; D000818:Animals; D004361:Drug Tolerance; D005260:Female; D007274:Injections, Intraperitoneal; D051379:Mice; D010433:Pentylenetetrazole; D010634:Phenobarbital / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*
D010433:Pentylenetetrazole; D010634:Phenobarbital