EFFECT OF (+ -OXEPINE-11-YL)-4-(3-PHENYL-2-PROPENYL)-PIPERAZINE DIMALEATE ON CEREBRAL VASOSPASM AND IMPAIRMENT OF CEREBRAL-CIRCULATION IN SUBARACHNOID HEMORRHAGE MODEL IN RATS/

A subarachnoid hemorrhage (SAH) model in rats was produced by the inje ction of homologous blood into the cisterna magna. Effect of AJ-3941 ( E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]-oxepine-11 -yl)-4(3-phenyl-2-pr openyl)-piperazine dimaleate, CAS 143110-70-7) on the development of c erebral vasospasm and the change of regional cerebral blood flow (rCBF ) following SAH was investigated in this model. Cerebral vasospasm fol lowing SAH showed a biphasic pattern with an early phase at 10 min and a late phase on 1 day after blood injection. The physiological parame ters (blood pressure, heart rate and blood gas contents) remained stab le within the physiological range throughout the course of the experim ent. AJ-3941 (0.01 mg/kg i.v. or 0.3 mg/kg p.o.) significantly prevent ed the development of late phase cerebral vasospasm. Cisternal injecti on of homologous blood significantly reduced rCBF immediately after th e injection and the reduction lasted during the observation period (30 min). Reduction in rCBF after the injection of homologous blood was p revented by AJ-3941 (0.01 mg/kg i.v.). rCBF in AJ-3941-treated rats co mpletely returned to the basal values after 30 min. The present result s suggest that AJ-3941 may be useful in the prevention of late spasm a nd in the improvement of cerebral circulation impaired with SAH.