flunarizine and ifenprodil

Baroreflex sensitivity assessed from the phenylephrine-induced reflex bradycardia was significantly decreased following 5 min global incomplete cerebral ischemia in pentobarbitalized dogs. Although bilateral vagotomy in the cervical region decreased baroreflex sensitivity by about 50% in sham-operated animals, it hardly affected the baroreflex in animals subjected to ischemia. The extent of the decrease in the influence of vagotomy on the baroreflex was dependent on the severity of ischemia in the dorsal medulla oblongata. In animals vagotomized before ischemia, no significant decrease in baroreflex sensitivity was observed following ischemia. Pretreatment with ifenprodil or flunarizine, 1 mg/kg i.v., 5 min prior to ischemia prevented the post-ischemic decrease in baroreflex sensitivity. Vagotomy decreased baroreflex sensitivity during the reperfusion period in these treated animals. These results suggest that the post-ischemic attenuation of reflex bradycardia may be due to a selective dysfunction of the vagal component of baroreflex, which can be prevented by the cerebroprotective agents.

Topics: Animals; Blood Pressure; Brain Ischemia; Cerebrovascular Circulation; Dogs; Female; Flunarizine; Heart Rate; Male; Piperidines; Pressoreceptors; Reflex; Vagotomy; Vagus Nerve; Vasodilator Agents

We studied the protective effects of pentobarbital, vinpocetine, flunarizine, and ifenprodil on delayed neuronal death using Mongolian gerbils. The animals were allowed to survive for 7 days after 5 min of cerebral ischemia induced by bilateral occlusion of the common carotid arteries. Hippocampal cell loss was quantified histologically 7 days following ischemia. Intraperitoneal application of pentobarbital (40 mg/kg) 30 min and vinpocetine (50 and 100 mg/kg) 10 min before ischemia significantly reduced neuronal cell loss in the CA1 sector. However, the intraperitoneal administration of flunarizine (10 and 30 mg/kg) and ifenprodil (10 and 30 mg/kg) 15 min before ischemia was not protective. The results suggest that pentobarbital and vinpocetine prevent ischemic neuronal damage, but not flunarizine and ifenprodil. These findings are of interest in relation to the mechanism of delayed neuronal death.

Topics: Animals; Cell Survival; Flunarizine; Gerbillinae; Hippocampus; Ischemic Attack, Transient; Male; Neurons; Pentobarbital; Piperidines; Vinca Alkaloids