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Increasing anticonvulsant effect of AD-810 (zonisamide) in aging BDF1 mice
Abstract:
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.
Insights
The anticonvulsant zonisamide (AD-810) is more effective in older mice, requiring lower doses to prevent seizures. This suggests reduced anticonvulsant dosages may be beneficial for elderly individuals.
Area of Science:
- Neuroscience
- Pharmacology
- Gerontology
Background:
- Aging can alter drug efficacy and dosage requirements.
- Understanding age-related changes in anticonvulsant effectiveness is crucial for optimizing treatment.
- Zonisamide (AD-810) is a novel anticonvulsant with a distinct mechanism of action.
Purpose of the Study:
- To evaluate the anticonvulsant efficacy of zonisamide (AD-810) across different age groups of mice.
- To determine if age influences the minimal effective concentration (MEC) of zonisamide.
- To compare the age-related effects of zonisamide with previously studied anticonvulsants.
Main Methods:
- Testing zonisamide's anticonvulsant activity in female BDF1 mice aged 7, 25, and 29 months.
- Measuring the minimal effective concentration (MEC) of zonisamide in plasma and brain.
- Inducing seizures using maximal electroshock (MES) to assess anticonvulsant efficacy.
Main Results:
- The MEC of zonisamide significantly decreased with age, indicating increased efficacy in older mice.
- Older mice (25- and 29-month-old) required 50% and 30% of the 7-month-old MEC, respectively.
- These findings align with previous studies on phenytoin, phenobarbital, and oxazepam.
Conclusions:
- The study supports the hypothesis that reduced anticonvulsant doses may be appropriate for the elderly.
- Age-related changes in seizure susceptibility, rather than drug-specific mechanisms, might explain increased efficacy in older animals.
- These findings have implications for optimizing anticonvulsant therapy in geriatric populations.