Experimental approach of treatment of cerebral ischemia by a combination of raubasine and almitrine.
Post-oligemic syndrome in rat results from transient reduction of cerebral blood flow obtained by bilateral carotid ligation for 60 min and mild systemic hypotension induced by s.c. injection of sodium nitroprusside. Over an acute phase of 3 days the syndrome consisted in a marked neurological deficit evidenced by a decrease in scores obtained by rats in "visual placing" test, a loss in learning ability substantiated by a decrease in the ability of rats to integrate and remember a passive avoidance reflex; biochemical disorders revealed by an increase in cerebral water, calcium and free fatty acids (FFA) contents associated with a decrease in cerebral potassium content. From 2 weeks until 4 weeks after ischemic insult a process of malacia of the cerebral tissue occurred. Treatment of rats with a combination of raubasine and almitrine (5023 SE, Duxil) by oral route (16.7 to 66.6 mg kg-1) twice daily from 1 h post-oligemia to sacrifice, in the acute phase, led to 1. an improvement of visual placing response, 2. an increase in learning ability, 3. a decrease in water and calcium cerebral contents associated with an increase in potassium cerebral contents. Enhancement of FFA contents was reduced when preventive treatment was associated with curative treatment. Incidence and extent of encephalomalacia was reduced by the drug in the chronic phase. It is concluded that in a rat model of post-oligemic syndrome and under these experimental conditions 5023 SE caused, 3 days after the ischemic insult, a significant reduction of cerebral disorders that may explain the therapeutic effect of the drug evidenced 4 weeks later.
D015765:Almitrine; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000473:pathology; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000523:psychology; D008297:Male; D009336:Necrosis; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D046948:Secologanin Tryptamine Alkaloids; D014882:Water-Electrolyte Balance / Q000187:drug effects; D015016:Yohimbine / Q000008:administration & dosage / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000697:Central Nervous System Stimulants; D005230:Fatty Acids, Nonesterified; D010879:Piperazines; D046948:Secologanin Tryptamine Alkaloids; D015016:Yohimbine; C005709:raubasine; D015765:Almitrine