The Pharmacological Effects Of Dl-3-n-Butylphthalide And Its Action Mechanisms

Dl-3-n-butylphthalide(dl-NBP), a new anti-cerebral ischemic drug, is being developed by our institute. L-NBP, primary derived from the seed of celery and synthesized by the Department of Medicinal Chemistry of our Institute, has been shown to improve brain energy metabolism after global cerebral ischemia, to reduce the infarct volume, attenuate delayed neuronal damage after focal cerebral ischemia, and to improve regional cerebral blood flow in ischemic brain. However, its action mechanism has not been clarified to explain its actions. In addition, previous studies of dl-NBP were confined to cerebral ischemia, however, hypoxia, subarachnoid hemorrhage, neurotrauma and cerebral ischemia always appears to induce similar pathophysiological insult in brain. Therefore, the possible therapeutic action of dl-NBP on subarachnoid hemorrhage and the closed head injury, the protective effects on reperfusion-induced brain injury after cerebral ischemia, and its mechanisms were evaluated in the present study.EFFECTS OF DL-NBP ON REGIONAL CEREBRAL BLOOD FLOW AND BLOOD-BRAIN BARRIER AFTER SUBARACHNOID HEMORRHAGESubarachnoid hemorrhage (SAH) was induced by injection of 0.35 ml autologous artery blood into lateral ventricle. Regional cerebral blood flow (rCBF)in caudate nucleus was determined by hydrogen clearance method. The results indicated that a rapid and marked decrease in rCBF in caudate nucleus was observed 15 min after SAH and the rCBF was remained at low level (about 50% pre-SAH value) within 180 min. Dl-NBP(50-100mg/kg, po) was shown to increase rCBF 30~180 min after the onset of SAH without significant effect on mean artery blood pressure. Dl-NBP (5-20 mg/kg, ip) was also shown to increase rCBF after SAH. The study also displayed that d-NBP but...