Effects of eptazocine, a novel analgesic, on KCN-induced changes in the cerebral contents of glycolytic metabolites and high-energy phosphates in mice.
Effects of eptazocine on cerebral metabolic changes due to a sublethal dose of KCN were investigated in mice. KCN (2 mg/kg, i.v.) induced a temporary loss of consciousness being moderated by eptazocine (1-10 mg/kg) in a dose-dependent manner. The KCN injection decreased the contents of phosphocreatine (PCr), ATP and glucose and increased the contents of AMP and lactate, resulting in a 34% decrease in energy charge potential (ECP) and an increase in lactate/pyruvate (L/P) ratio. Such changes were improved by eptazocine (10 mg/kg) and EKC (3 mg/kg), but not by pentazocine (10 mg/kg) and morphine (3 mg/kg), and the improving effect of eptazocine was completely inhibited by MR-2266 (3 mg/kg), a relatively selective opioid kappa-receptor antagonist. On the other hand, eptazocine (3, 10 mg/kg) was found to increase the glucose content in normal mice, but not to give significant changes in the contents of glycolytic metabolites and high-energy phosphates. These results suggest that eptazocine may improve anoxic changes in cerebral energy metabolism.
Tamura
T
T
Central Research Laboratories, Nihon Iyakuhin Kogyo Co., Ltd., Toyama, Japan.
Taniguchi
T
T
Miyamoto
T
T
Aoki
M
M
Waki
I
I
D000249:Adenosine Monophosphate / Q000032:analysis*; D000255:Adenosine Triphosphate / Q000032:analysis*; D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D003243:Consciousness / Q000187:drug effects; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000032:analysis; D007275:Injections, Intravenous; D007773:Lactates / Q000032:analysis; D019344:Lactic Acid; D008297:Male; D051379:Mice; D010725:Phosphocreatine / Q000032:analysis; D011190:Potassium Cyanide / Q000008:administration & dosage / Q000633:toxicity*
D001575:Benzomorphans; D007773:Lactates; D010725:Phosphocreatine; C033776:eptazocine; D019344:Lactic Acid; D000249:Adenosine Monophosphate; C027247:MR 2266; D000255:Adenosine Triphosphate; D005947:Glucose; D003496:Cyclazocine; D011190:Potassium Cyanide