Evaluation of Isonicotinoyl-γ-Aminobutyric Acid (GABA) and Nicotinoyl-GABA as Pro-drugs of GABA

• Published in: Chemical & pharmaceutical bulletin Vol. 32; no. 10; pp. 4089 - 4095
• Main Authors: MATSUYAMA, KENJI, YAMASHITA, CHIKAMASA, NODA, ATSUKO, GOTO, SHIGERU, NODA, HIROSHI, ICHIMARU, YASUYUKI, GOMITA, YUTAKA
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.01.1984; Maruzen
• Subjects: Animals; Behavior, Animal - drug effects; Biological and medical sciences; Brain - metabolism; Chemistry, Pharmaceutical; gamma-Aminobutyric Acid - analogs & derivatives; gamma-Aminobutyric Acid - metabolism; gamma-Aminobutyric Acid - pharmacology; GC-MS; General pharmacology; Male; Medical sciences; Mice; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; GABA; Purification; Prodrug; Structure activity relation; Preparation
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.32.4089

Isonicotinoyl-γ-aminobutyric acid (GABA) (IG) and nicotinoyl-GABA (NG), candidate prodrugs of GABA, were assessed by measuring various pharmacological responses such as anticonvulsant effect, prolongation of pentobarbital sleeping time and depressive effect on rearing or ambulation in general behavior, in relation to the GABA level in the mouse brain. The GABA level after the intraperitoneal administration of IG at a dose of 1000 mg/kg increased significantly from 2.30±0.02μmol/g wet wt. in the control to 2.93±0.05μmol/g wet wt., while NG caused only a slight increase in GABA level. IG showed a stronger anticonvulsant effect, greater prolongation of pentobarbital sleeping time and greater depressive effect on rearing in general behavior than NG did. The pharmacological effect of IG or NG corresponded well to the GABA level in the brain.