Hyperthermia induced in rabbits by organic calcium antagonists.
Verapamil, nifedipine and cinnarizine, when injected intracerebroventricularly (ICV), induced a rise in core temperature related to the dose of the drug and accompanied by vasoconstriction of the ear vascular bed. On the contrary, the calcium channel activator BAY-K-8644, structurally related to nifedipine, elicited a dose-related hypothermic response which was accompanied by vasodilatation. The delay in onset of verapamil-induced hyperthermia was reduced by pretreating the animals with a dose of acetylsalicylic acid (ASA) which antagonized fever induced by E. coli endotoxin. BAY-K-8644 was shown to partially antagonize E. coli endotoxin-induced fever. These findings indicate that neurons responsible for temperature control are a target of organic calcium antagonists and suggest that calcium metabolism is of primary importance in the function of these cells.
Palmi
M
M
Centro Interdipartimentale di Ricerca sul Metabolismo dei Farmaci Psicotropi Istituto di Scienze Farmacologiche, Siena, Italy.
Sgaragli
G
G
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002936:Cinnarizine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D011817:Rabbits; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004731:Endotoxins; D002936:Cinnarizine; C044101:endotoxin, Escherichia coli; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D009543:Nifedipine