Amlodipine, an L‐type calcium channel blocker, protects against chlorpromazine‐induced neurobehavioural deficits in mice

Abstract

This study investigated the modulatory and chemopreventive benefit of amlodipine (AML), a dihydropyridine calcium channel antagonist, against neurobehavioural abnormalities (NAs) associated with chlorpromazine (CPZ) toxicity in mice. Adult mice were divided into five groups of six animals/group. Group 1 (control) was administered saline (10 mL/kg i.p.). Group 2 received CPZ (2 mg/kg i.p.). Groups 3 and 4 received bromocriptine (BMC, 2.5 mg/kg s.c.) and AML (1 mg/kg s.c.), respectively, while group 5 received their combination. Groups 3-5 later received CPZ 30 min after initial treatments. Animals were subjected to neurobehavioural tests and euthanized 18 h later. CPZ-induced NAs were characterized by significant increase (P < 0.001) in cataleptic behaviour and lowered (P < 0.05) spontaneous activity reaction time in mice. There were also significant (P < 0.001) increases in malondialdehyde levels and decreased locomotion plus learning and memory parameters (P < 0.05-0.001). AML pretreatment alone did not alleviate CPZ-induced motor deficits in the mice. While pretreatment with BMC alone attenuated CPZ-associated catalepsy, its combination with AML further protected mice against NAs. Furthermore, BMC pretreatment did not affect CPZ-induced increase in malondialdehyde level, but AML or BMC+AML significantly (P < 0.05) decreased malondialdehyde in the CPZ-treated rats. Reduced glutathione levels and activities of superoxide dismutase and catalase remained elevated in all treatment groups. In conclusion, data from this study suggest possible chemopreventive benefit of AML alone or in combination with BMC against CPZ-associated neurobehavioural deficits. The ameliorative effect of AML may be related to its antioxidant and/or calcium channel blocking property.

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Bufalin, a bufanolide steroid from the parotoid glands of the Chinese toad, suppresses hERG K+ currents expressed in HEK293 cells

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Single-Pass Albumin Dialysis as Rescue Therapy for Pediatric Calcium Channel Blocker Overdose

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