Hydrazonopropionic acid, a new class of hypoglycemic substances. 2. Influence of 2-(phenylethylhydrazono)- and 2-(2-cyclohexyl-ethylhydrazono)-propionic acid on redox systems, acid base status and monoamino oxidase activity.
Phenylethylhydrazono-propionic acid (PEHP) and cyclohexyl-ethylhydrazono-propionic acid (CHEHP) has been shown to lower blood glucose concentrations in various laboratory animals after intraperitoneal or oral application. The present study has been conducted to investigate, if these hydrazones may induce lactic acidosis like the biguanides or may cause unwanted side reactions due to an inhibition of monoamino oxidase like the corresponding hydrazines. It was found that intramitochondrial and cytoplasmatic redox ratios were not influenced at a hypoglycemic effective dosage (145 mumol/kg body weight) of these substances in fasted guinea pigs. An effect on the acid base status was not observed. Both substances lowered the concentration of ketone bodies in fasted guinea pigs. In vitro the activity of monoamino oxidase purified from guinea pig liver was much less inhibited by the hydrazones than by one of the corresponding hydrazines (phenelzine). Furthermore CHEHP (145 mumol/kg body weight) did not influence the serum activity of various liver enzymes and the concentration of triglycerides, cholesterol and uric acid in plasma of fasted guinea pigs. It is concluded that CHEHP meets basic requirements for a potential oral antidiabetic agent.
D000090:Acetoacetates / Q000097:blood; D000136:Acid-Base Equilibrium / Q000187:drug effects*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005215:Fasting; D006168:Guinea Pigs; D006835:Hydrazones / Q000494:pharmacology*; D006885:Hydroxybutyrates / Q000097:blood; D007004:Hypoglycemic Agents; D007773:Lactates / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D010084:Oxidation-Reduction; D010624:Phenelzine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology*; D011773:Pyruvates / Q000097:blood
D000090:Acetoacetates; D001786:Blood Glucose; D006835:Hydrazones; D006885:Hydroxybutyrates; D007004:Hypoglycemic Agents; D007773:Lactates; D011422:Propionates; D011773:Pyruvates; C020926:2-(phenylethylhydrazono)propionic acid; C020877:2-(2-cyclohexylethylhydrazono)propionic acid; D008995:Monoamine Oxidase; D010624:Phenelzine