The cerebral protective effect of
eptazocine, an
opioid mu-antagonist-kappa-agonist, was investigated using mice and rats subjected to
ischemia. 1)
Decapitation or concussive
head injury (20 g, 30 cm)-induced
ischemia in mice:
Eptazocine (3,10 mg/kg) prolonged the gasping duration or the survival time in a dose-dependent manner. 2) Ischemic
brain edema induced by bilateral carotid
arterial occlusion (BLCO) in rats: Administration of
eptazocine just after BLCO treatment significantly prevented the incidence of ischemic
seizures, lethality and an increase in cerebral water content. 3) Acute ischemic changes in cerebral energy metabolism in mice: 2-min BLCO treatment decreased the cerebral contents of
phosphocreatine and
ATP, and it increased the contents of
AMP and
lactate, resulting in a 34% decrease in energy charge potential and an increase in
lactate/
pyruvate ratio. Such changes were improved by
eptazocine (3, 10 mg/kg) and
ethylketocyclazocine (3 mg/kg), a kappa-agonist. 4) Respiratory function in mouse brain mitochondria preparations:
Eptazocine increased the State 3 respiration and respiratory control index (RCI:State 3/State 4), and it prevented a decrease in RCI induced by 3-min
ischemia. These results suggest that
eptazocine may improve cerebral ischemic disorders through an activation and/or protection of mitochondrial energy-producing systems.