Jpn. J. Pharmacol. 76 (3), 297-304 (1998)

Effect of 5-{3-[((2S)-1,4-Benzodioxan-2-ylmethyl)amino]propoxy}-1,3-benzodioxole HCl (MKC-242), a Novel 5-HT1A-Receptor Agonist, on Aggressive Behavior and Marble Burying Behavior in Mice

Michikazu Abe (1), Hiroshi Nakai(2), Reiko Tabata (1), Ken-Ichi Saito (1) and Mitsuo Egawa (3)

(1) Pharmaceuticals Laboratory I, (2) Pharmacokinetics and Metabolism Research Laboratory, Yokohama Research Center, Mitsubishi Chemical Corporation, 1000, Kamoshida, Aoba-ku, Yokohama 227-8502, Japan
(3) Clinical Research Department, Mitsubishi Chemical Corporation, Shinagawa-ku, Tokyo 140-0002, Japan

Abstract: Behavioral effects of 5-{3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy}-1,3-benzodioxole HCI (MKC-242), a novel 5-HT1A-receptor agonist, were evaluated using animal models of anxiety and obsessive compulsive disorder and compared against reference compounds. MKC-242 suppressed foot shock-induced fighting behavior without loss of motor coordination in mice as the reference compounds did. The ED50 values of MKC-242, buspirone, tandospirone and diazepam were 1.7, 42, 80 and 2.0 mg/kg, p.o., respectively. The duration of the suppression of fighting by MKC-242 was longer than those of buspirone and tandospirone and comparable to that of diazepam. Similar results were also obtained with the water-lick conflict test in rats. The plasma concentration of MKC-242 in rats was much higher than the reported value of buspirone during 0.25 - 6 hr after oral administration. In addition, MKC-242 reduced marble burying behavior without reduction of motor activity. Fluoxetine, tandospirone and diazepam also reduced the behavior at non-sedative doses. These findings indicate that MKC-242 possesses a longer-lasting anxiolytic effect than azapirones. This might be due to the high concentration of the compound in plasma. In addition, it is also suggested that MKC-242 possesses an antiobsessional effect.

Keywords: MKC-242, 5-HT1A receptor, Anxiolytic, Aggressive behavior, Marble burying behavior

Copyrightę The Japanese Pharmacological Society 1998

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