Pharmacological Properties of SM-3997: A New Anxioselective Anxiolytic Candidate

• Published in: Japanese journal of pharmacology Vol. 45; no. 4; pp. 493 - 500
• Main Authors: SHIMIZU, Hiroshi, HIROSE, Akira, TATSUNO, Tohru, NAKAMURA, Mitsutaka, KATSUBE, Junki
• Format: Journal Article
• Language: English
• Published: Kyoto Japanese Pharmacological Society 1987
• Subjects: Anesthesia; Animals; Anti-Anxiety Agents - pharmacology; Anticonvulsants; Biological and medical sciences; Conflict (Psychology); Drug Synergism; Isoindoles; Male; Medical sciences; Mice; Mice, Inbred Strains; Motor Activity - drug effects; Muscle Relaxants, Central; Neuropharmacology; Pharmacology. Drug treatments; Piperazines - pharmacology; Postural Balance - drug effects; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Pyrimidines - pharmacology; Rats; Rats, Inbred Strains; Receptors, Dopamine - drug effects; Vertebrata; Mammalia; Tranquillizer; Rat; Mouse; Animal; Rodentia; Anxiety; Comparative study
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)43370-2

Pharmacological properties of SM-3997 (3aα,4β,7β,7aα-hexahydro-2-(4-(4-(2-pyrimidinyl)-1 -piperazinyl)-butyl)-4,7-methano-1 H-isoindole-1,3(2H)-dione dihydrogen citrate) have been examined in rats and mice. SM-3997 showed a dose-related anticonflict activity in rats in a water lick conflict paradigm, and it had no effect on water consumption in a spontaneous water drinking test. The potency of SM-3997 appeared to be equal to that of buspirone and about one-half that of diazepam. No tolerance to the anticonflict activity of SM-3997 was observed following 5 and 10 consecutive days of treatment. Unlike diazepam, SM-3997 had no anticonvulsant effect and had very weak muscle relaxant and hypnotic effects. On the other hand, SM-3997 and buspirone exhibited dopamine antagonistic action, although the potency of SM-3997 was less than one fourth that of buspirone. These results show that SM-3997 is a new anxioselective anxiolytic agent which is weaker than buspirone in the dopaminergic neuron system.