Increasing anticonvulsant effect of AD-810 (zonisamide) in aging BDF1 mice.
The anticonvulsant efficacy of a newly developed anticonvulsant, AD-810 (zonisamide, 3-sulfamoylmethyl-1,2-benzisoxazole) was examined in relation to mouse age in three different age groups of female BDF1 mice (7-, 25- and 29-month-old). The minimal effective concentration (MEC) of AD-810 in both plasma and brain for abolishing the electroshock-induced maximal seizure steadily decreased with age, the 25- and 29-month values being 50 and 30% of respective 7-month values. The observation in the present study was almost identical to previous observations by the authors on phenytoin, phenobarbital and oxazepam. The present results support our previous contention that the dose and plasma concentration of anticonvulsants can (and probably should) be reduced in the elderly regardless of the drug. Since the anticonvulsant mechanism of AD-810 has been reported to differ from those of previously examined drugs (phenobarbital and oxazepam), the results also suggest that the apparent increase in the pharmacological effect of these anticonvulsants may be due to old animals' lowered response capability for seizures rather than a specific age effect on the pharmacological reaction sites for individual anticonvulsants.
D000375:Aging; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007555:Isoxazoles / Q000008:administration & dosage* / Q000378:metabolism; D051379:Mice; D010080:Oxazoles / Q000008:administration & dosage*; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D010080:Oxazoles; D000078305:Zonisamide