title: Effects in cats of atipamezole, flumazenil and 4-aminopyridine on stress-related neurohormonal and metabolic responses induced by medetomidine, midazolam and ketamine.
abstract: This study aimed to investigate the antagonistic effects of a fixed dose of atipamezole (ATI), flumazenil (FLU) and 4-aminopyridine (4AP), both alone and in various combinations, on key stress-related neurohormonal and metabolic changes induced by medetomidine (MED), midazolam (MID) and ketamine (KET) in healthy cats. Seven cats were used consistently in eight investigation groups. Cats were administered a mixture of 0.05 mg/kg MED and 0.5 mg/kg MID followed 10 mins later by 10 mg/kg KET intramuscularly. Twenty minutes after KET injection, the cats were intravenously injected with either a physiological saline solution at 0.1 ml/kg (control) or one of the seven variations of experimental drugs, alone or in combination: ATI, FLU, 4AP, ATI + FLU, FLU + 4AP, ATI + 4AP and ATI + FLU + 4AP. Blood samples were collected 10 times during the 24 h test period. Plasma glucose, insulin, cortisol, epinephrine, norepinephrine and non-esterified fatty acid levels were measured. The administration of MED + MID + KET resulted in hyperglycaemia and decreases in epinephrine, norepinephrine, cortisol and non-esterified fatty acid levels. FLU or 4AP alone or FLU + 4AP did not effectively antagonise the effects induced by MED + MID + KET but enhanced the hyperglycaemia. ATI alone was effective in antagonising these effects. Compared with non-ATI regimens, combinations with ATI were more effective in antagonising the effects induced by MED + MID + KET; however, ATI + FLU + 4AP caused large increases in cortisol, epinephrine and norepinephrine concentrations. ATI, both alone and in combination, is effective in antagonising the neurohormonal and metabolic effects of MED + MID + KET in cats. However, ATI + FLU + 4AP is not suitable because of large stress-related hormonal responses.
authors.affiliation: Laboratory of Veterinary Internal Medicine, Joint Department of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori, Japan Ueoka Animal Hospital, Hiroshima, Japan.
authors.forename: Naotami
authors.initials: N
authors.lastname: Ueoka
authors.affiliation: Laboratory of Veterinary Internal Medicine, Joint Department of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori, Japan hikasa@muses.tottori-u.ac.jp.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hikasa
mesh_terms: D015761:4-Aminopyridine / Q000008:administration & dosage*; D000758:Anesthesia / Q000662:veterinary*; D019162:Anesthetics, Combined / Q000008:administration & dosage; D000818:Animals; D001143:Arousal / Q000187:drug effects; D002415:Cats / Q000378:metabolism* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000008:administration & dosage*; D007093:Imidazoles / Q000008:administration & dosage*; D007649:Ketamine / Q000494:pharmacology*; D020926:Medetomidine / Q000494:pharmacology; D008874:Midazolam / Q000494:pharmacology*; D012119:Respiration / Q000187:drug effects
chemical_list: D019162:Anesthetics, Combined; D007093:Imidazoles; C050701:atipamezole; D005442:Flumazenil; D007649:Ketamine; D015761:4-Aminopyridine; D020926:Medetomidine; D008874:Midazolam