The effects of a new eburnamenine derivative (3 beta,14 alpha, 16 alpha)-(+/-)-14,15-dihydro-20,21-dinoreburnamenin-14-ol (
vindeburnol,
RU 24722) on EEG, on brain energy metabolism and on local cerebral blood flow (LCBF) and in different experimental models of cerebral insufficiency were compared with those of
vincamine,
vinburnine (1-eburnamonine),
dihydroergotoxine mesilate and
nicergoline.
Vindeburnol at 2 mg/kg i.v., increased the EEG resistance time in rats subjected to
asphyxia anoxia and
at 10 mg/kg s.c., significantly improved the electrocortical recovery of gerbils subjected to a 10-min
cerebral ischemia.
Vindeburnol (10 mg/kg i.p.) significantly retarded
glucose,
phosphocreatine and
adenosine triphosphate utilization and
lactate production in mouse brain during 10 s of
decapitation ischemia. The cerebral metabolic rate was 10.34 mmol/kg/min, which was about 50% of the control value.
At 10 mg/kg i.p., the product induced a slight and transient increase in LCBF.
Vincamine improved the early phase of the postischemic electrocortical recovery in the gerbil, had no effect on cerebral energy substrates and slightly increased the LCBF for 15 min.
Dihydroergotoxine mesilate improved the early phase of the electrocortical recovery in gerbils subjected to
ischemia, did not significantly modify the energy substrates and rapidly increased the LCBF, which was normal after 30 min.
Vinburnine and
nicergoline were inactive in the cerebral insufficiency models used and did not significantly modify cerebral energy metabolism. These results show that
vindeburnol has a different pharmacological profile from
vincamine,
vinburnine,
dihydroergotoxine mesilate and
nicergoline, and suggest that
vindeburnol may be therapeutically effective in cerebral insufficiency.