The effects of dihydroergocryptine on the neurological and enzyme disorders induced by cerebral ischaemia in rats.
Ergot alkaloids are commonly used as cerebroprotective drugs. Their efficacy has been demonstrated experimentally in animals submitted to acute cerebral anoxia or ischaemia, at dose levels hugely superior to dose levels usually administered in humans. In the present experiments, dihydroergocryptine (DHEC), a constituent of dihydroergotoxine (DHET), was administered at doses closely related to human doses, preventively (in experiments where animals survived only for a short while after ischaemic insult) or curatively, and its efficacy tested through refined neurological and biochemical evaluation of experimental cerebral ischaemia sequelae. DHEC was administered orally (30 micrograms or 150 micrograms/kg body weight (bwt) twice daily) for 3 days, following transient cerebral ischaemia induced by a 60-min carotid occlusion plus sodium nitroprusside (1.1 mg/rat s.c.) injection, or, in a second experiment, prophylactically (60 micrograms or 300 micrograms/kg bwt/day) for 4 days prior to multiple cerebral infarct induced by sodium arachidonate injection into the left internal carotid artery. The neurological sequelae were evaluated by the Irwin visual placing response or by a battery of behavioural tests. Na-K-ATPase enzyme activity in cerebral homogenates was measured; decreases in this enzyme activity are considered to reflect the neuronal membrane consequences of the neurocell energetic metabolism alterations caused by cerebral ischaemia. Low dose oral DHEC treatment prevented the behavioural abnormalities and memory impairment arising after transient cerebral ischaemia and there was a marked trend in improving the behavioural abnormalities observed in animals submitted to massive cerebral infarction, in spite of the model severity. DHEC prevented reduction in cerebral Na-K-ATPase activity after cerebral multiinfarction. These effects of DHEC were observed with doses and administration route close to the usual therapeutic regimen.
Cahn
R
R
SIR International, Department of Experimental Therapy, Montrouge, France.
Borzeix
M G
MG
Legeai
J
J
D000818:Animals; D001921:Brain / Q000201:enzymology; D002545:Brain Ischemia / Q000188:drug therapy*; D002544:Cerebral Infarction / Q000188:drug therapy; D004088:Dihydroergotoxine / Q000627:therapeutic use*; D008297:Male; D009460:Neurologic Examination; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D004088:Dihydroergotoxine; D000254:Sodium-Potassium-Exchanging ATPase