title: 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.
authors.affiliation: Department of Pharmacology, Benjamin Carson (Snr.) School of Medicine, Babcock University, Ilisan-Remo, Ogun State, 21244 Ikeja, Nigeria.|Department of Pharmacology, Therapeutics and Toxicology, College of Medicine, University of Lagos, P.M.B 12003 Idi-Araba, Lagos, Nigeria.
authors.forename: Oluwafemi E
authors.initials: OE
authors.lastname: Kale
authors.affiliation: Department of Pharmacology, Therapeutics and Toxicology, College of Medicine, University of Lagos, P.M.B 12003 Idi-Araba, Lagos, Nigeria.
authors.forename: Olufunsho
authors.initials: O
authors.lastname: Awodele
authors.affiliation: Department of Pharmacology, Therapeutics and Toxicology, College of Medicine, University of Lagos, P.M.B 12003 Idi-Araba, Lagos, Nigeria.
authors.forename: Temitope F
authors.initials: TF
authors.lastname: Ogundare
authors.affiliation: Department of Pharmacology, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana.
authors.forename: Martins
authors.initials: M
authors.lastname: Ekor
mesh_terms: D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001971:Bromocriptine / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002746:Chlorpromazine / Q000009:adverse effects*; D005978:Glutathione / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D020011:Protective Agents / Q000494:pharmacology*; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D020746:Calcium Channels, L-Type; D020011:Protective Agents; D017311:Amlodipine; D001971:Bromocriptine; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D002746:Chlorpromazine
keywords: amlodipine; antioxidant; chlorpromazine; neurobehavioural action