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Effects of calcium channel blockers on impairment of brain function in senescence-accelerated mice
M Yamamoto1, M Suzuki, Y Ozawa
1Department of Pharmacology, Clinical Pharmacology Research Laboratory, Yamanouchi Pharmaceutical Co., Ltd., Tokyo, Japan.
Abstract:
The effects of the L-type calcium channel blockers, nicardipine, nimodipine, nilvadipine and amlodipine, on brain dysfunction were examined in senescence-accelerated-prone mice. A disturbed brain function in passive avoidance response, forced swimming, rota-rod and traction tests was observed in senescence-accelerated-prone mice compared to senescence-accelerated-resistant mice. A single oral administration of the four calcium channel blockers tested had little effect on the brain dysfunction in senescence-accelerated-prone mice. In contrast, the daily oral administration of nicardipine (1 and 3 mg/kg), nimodipine (3 mg/kg) and nilvadipine (3 mg/kg), once a day for three weeks, prolonged the shortened latency of step-through in the passive avoidance response and falling time in rota-rod tests. Brain dysfunction in forced swimming and traction tests was not influenced by repeated administration of these blockers. Repeated administration of amlodipine for three weeks in senescence-accelerated-prone mice showed little pharmacological actions in all four tests. Thus, we found that repeated administration of nicardipine, nimodipine and nilvadipine ameliorated the brain dysfunction in these mice. Furthermore, the present study suggests that senescence-accelerated-prone mice can be used as an appropriate model for evaluating the pharmacological effects of calcium channel blockers on brain dysfunction.
Insights
Repeated use of nicardipine, nimodipine, and nilvadipine improved brain function in aging mice. These L-type calcium channel blockers show potential for treating age-related cognitive decline.
Area of Science:
- Neuroscience
- Pharmacology
- Gerontology
Background:
- Brain dysfunction is a hallmark of aging.
- Senescence-accelerated-prone (SAP) mice exhibit impaired cognitive and motor functions.
- L-type calcium channel blockers are investigated for neuroprotective effects.
Purpose of the Study:
- To evaluate the efficacy of four L-type calcium channel blockers (nicardipine, nimodipine, nilvadipine, amlodipine) in ameliorating brain dysfunction in SAP mice.
- To assess the potential of SAP mice as a model for studying age-related brain dysfunction and therapeutic interventions.
Main Methods:
- Senescence-accelerated-prone (SAP) mice and senescence-accelerated-resistant (SAR) mice were used for comparison.
- Cognitive and motor functions were assessed using passive avoidance response, forced swimming, rota-rod, and traction tests.
- Mice received single or repeated daily oral administration of L-type calcium channel blockers for three weeks.
Main Results:
- SAP mice demonstrated significant brain dysfunction compared to SAR mice.
- Repeated administration of nicardipine, nimodipine, and nilvadipine improved performance in passive avoidance and rota-rod tests.
- Single administration and repeated amlodipine treatment showed minimal effects on brain dysfunction in SAP mice.
Conclusions:
- Nicardipine, nimodipine, and nilvadipine show therapeutic potential in ameliorating specific aspects of brain dysfunction associated with aging.
- Senescence-accelerated-prone mice serve as a valuable model for evaluating the pharmacological effects of calcium channel blockers on brain aging.