The Cerebroprotective Properties of Cereprotex (2,4,6,8-tetramethyl-2,4,6,8-tetraazabicyclo[3.3.0]-octane-3,7-dione) after traumatic and hypoxic brain injury

The cerebroprotective effect of Cereprotex (Patent pending – Cereprotec Inc. www.cereprotec.com ) (2,4,6,8-tetramethyl-2,4,6,8-tetraazabicyclo[3.3.0]-octane-3,7-dione) , previously known as (CombiCNS1), was assessed in a model of closed head injury in mice. This type of trauma produces brain edema (i.e. increase in water content), breakdown of the blood brain barrier (BBB) and functional impairment. The effect of treatment with Cereprotex, administered 1 h after injury on brain edema and on neurobehavioral function was assessed 24 h later. While spontaneous improvement of function was observed in 2 mice out of 10 (20 %) in the control, non-treated group, treatment with Cereprotex resulted in the improved recovery of 5 mice out of 9 (55.5 %). Moreover, significant (p<0.05) decrease in the degree of edema developed after injury was found following treatment with Cereprotex. About 35% less water accumulated in the traumatized hemisphere of the Cereprotex treated mice, as compared with vehicle-treated animals. Water content in the contralateral hemisphere reverted to normal levels.

Antihypoxic effect was evaluated in two in vivo models: a) The hypercapnic normobaric hypoxia in mice b) The hypobaric hypoxia in rats (dose-response)

Cereprotex has impressive antihypoxic effect; it prolonged significantly convulsion latency at 84% and survival time of mice at 78,4%. Cereprotex exerted a dose dependent antihypoxic effect. Doses of 100, 250 and 500 mg/kg exhibited significantly increasing survival time by 162%, 275%, and 425%, respectively, as compared to control group, in a model of hypoxia.