Pharmacological Characterization of the Novel Anxiolytic β-Carboline Abecarnil in Rodents and Primates

• Published in: Japanese journal of pharmacology Vol. 64; no. 3; pp. 179 - 188
• Main Authors: Ozawa, Masaki, Nakada, Yukie, Sugimachi, Keiko, Yabuuchi, Fumie, Akai, Tetsuo, Mizuta, Eiji, Kuno, Sadako, Yamaguchi, Motonori
• Format: Journal Article
• Language: English
• Published: Kyoto The Japanese Pharmacological Society 1994; Japanese Pharmacological Society
• Subjects: Abecarnil; Aggression - drug effects; Animals; Anti-Anxiety Agents - metabolism; Anti-Anxiety Agents - pharmacology; Anxiolytic; Behavior, Animal - drug effects; Benzodiazepines; Benzodiazepines - pharmacology; Binding, Competitive; Biological and medical sciences; Carbolines - metabolism; Carbolines - pharmacology; Cerebellum - drug effects; Cerebellum - metabolism; Cerebellum - ultrastructure; Flumazenil - metabolism; GABA; Hexobarbital - pharmacology; Kidney - drug effects; Kidney - metabolism; Kidney - ultrastructure; Macaca fascicularis; Male; Medical sciences; Mice; Mice, Inbred ICR; Motor Activity - drug effects; Neuropharmacology; Pharmacology. Drug treatments; primates; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Wistar; Receptors, GABA-A - classification; Receptors, GABA-A - drug effects; Receptors, GABA-A - metabolism; Reflex - drug effects; Spinal Cord - drug effects; Spinal Cord - metabolism; Spinal Cord - ultrastructure; Tritium; β-Carboline; GABA; β-Carboline; Abecarnil; Anxiolytic; Benzodiazepines; Psychotropic; Rodentia; Anxiety disorder; Oral administration; Vertebrata; Chemotherapy; Mammalia; Carboline derivatives; Treatment; Tranquillizer; Animal; Primates; Anxiety; Comparative study
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.64.179

β-Carboline abecarnil was behaviorally and biochemically characterized as a new anxiolytic agent in rodents and primates in comparison with the benzodiazepine (BZ) anxiolytics. Oral treatment with abecarnil (0.5 – 10 mg/kg) showed a potent anticonflict activity in the water-lick test in rats. The minimal effective dose was lower than those of BZ anxiolytics, such as etizolam, diazepam, clotiazepam and tofisopam. Abecarnil also showed taming effects to suppress fighting and aggressive behaviors in mice and monkeys with little sedative and ataxic effects, in contrast to the BZ anxiolytics producing marked sedative and ataxic effects. Furthermore, abecarnil suppressed both the sedative and ataxic effects induced by diazepam. Abecarnil bound to rat cerebellar BZ1, receptors (Ki = 0.24 nM) with a higher affinity than to rat spinal cord BZ2 receptors (Ki = 1.3 nM), whereas BZ derivatives bound to both the receptors with a low and equal affinity. GABA-ratios of abecarnil were 1.9 for the BZ1 receptors and 2.8 for the BZ2 receptors, and they were smaller than those of diazepam and flunitrazepam. Thus, in contrast to the BZ derivatives, abecarnil may act as a selective partial agonist at central BZ1 receptors, resulting in its potent anticonflict and taming effects with little sedative and ataxic effects.