Experimental approach of activity and mechanism(s) of action of drugs used in cerebral metabolic insufficiency. Application to 1-eburnamonine.
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.
D019794:2,3-Diphosphoglycerate; D000255:Adenosine Triphosphate / Q000097:blood; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004163:Diphosphoglyceric Acids / Q000097:blood; D004285:Dogs; D004912:Erythrocytes / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051379:Mice; D011817:Rabbits; D051381:Rats; D014748:Vinca Alkaloids / Q000494:pharmacology*
D004163:Diphosphoglyceric Acids; D014748:Vinca Alkaloids; D019794:2,3-Diphosphoglycerate; D000255:Adenosine Triphosphate; D005947:Glucose; C016422:eburnamonine