Effect of milacemide, a glycinamide derivative, on the rat brain gamma-aminobutyric acid system.
Milacemide (CP 1552 S, 2-n-pentylaminoacetamide), a drug with anti-epileptic potency, increases the gamma-aminobutyric acid (GABA) content specifically in the substantia nigra of rat brain. The effect is dose-related from 25 to 100 mg/kg p.o. The time course shows that at 100 mg/kg p.o. after 2, 3 and 4 hr the substantia nigra GABA content is significantly increased by 28, 33 and 38%, respectively. After 6 hr the GABA contents return to the control value. After repeated oral administration of milacemide a comparable effect to acute administration is obtained. After degeneration of the striato-nigral GABA-ergic pathway, milacemide no longer enhances the content of GABA in the substantia nigra. GABA-transaminase activity measured ex vivo in rat brain homogenate is not influenced by milacemide. On the other hand, the glutamate decarboxylase activity measured ex vivo 3 hr after 100 mg/kg of milacemide is significantly increased by 11% in homogenates of the whole rat brain. The results show that milacemide increases the GABA content in the GABA pool which is associated with the striato-nigral neurons. This increase is not due to GABA-transaminase inhibition but might be the result of an enhanced synthesis, possibly through glutamate decarboxylase activation.
D000081:Acetamides / Q000494:pharmacology*; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000081:Acetamides; C039332:milacemide; D000625:Aminooxyacetic Acid; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid