Experimental Approach of Activity and Mechanism(s) of Action of Drugs Used in Cerebral Metabolic Insufficiency

Abstract

The authors described an experimental approach, specially using oral administration, of drugs used in cerebral metabolic insufficiencies and its application to l-eburnamonine (l-EB). Administered orally, l-EB: (1) significantly increased the cerebral consumption of [¹⁴C]-deoxyglucose in normoxic mice; (2) decreased the fall in cerebral energy charge (ECP) of rats after an acute normobaric hypoxia, and (3) stimulated the glycolysis of red blood cells (RBC) in healthy volunteers (repeated administrations) as demonstrated by important increases in 2,3-DPG and ATP, i.e., in factors involved in the bioavailability of oxygen (oxygen transport activity and RBC deformability). The results therefore demonstrate oral activity of l-EB in animals and man. They are in agreement with previous data showing cerebral metabolic stimulant and antihypoxic effects following parenteral administration, in animals. They allow to propose that l-EB acts both at cerebral and extracerebral levels and constitute objective biochemical proof of the activity of l-EB in man. The study of new drugs may be done using the same experimental approach.

Eburnamine derivatives and the brain

“…Linee et al 21 have found that orally administered L-eburnamonine significantly increased the cerebral consumption of [ 14 C]deoxyglucose in normoxic mice, decreased the fall in cerebral energy charge of rats after an acute normobaric hypoxia and stimulated the glycolysis of red cells in healthy volunteers. There were increases in red blood cell ATP and 2,3-diphosphoglycerate contents suggesting increased red blood cell deformability.…”

Synthesis and Evaluation of 2′-Hydroxyethyl trans-Apovincaminate Derivatives as Antioxidant and Cognitive Enhancer Agents

“…Earlier structure–activity relationship (SAR) studies showed the effects of different changes in the structure of the eburnane skeleton. The cerebrovascular activity is closely related to a specific configuration, namely, the natural cis -(3 S ,16 S )-eburnane skeleton, which can be identified in 1 and 2 , as well as in (−)-eburnamonine (vinburnine, 3 ), the latter two compounds are also marketed as cerebrovasculars. (Figure ).…”