EFFECT OF ODIOXAN-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

Behavioral effects of 1,4-benzodioxan-2ymethyl)amino]propoxy}-1,3-benz o- dioxole HCI (MKC-242), a novel 5-HT1A-receptor agonist, were evalua ted using animal models of anxiety and obsessive compulsive disorder a nd 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., respe ctively. The duration of the suppression of fighting by MKC-242 was lo nger than those of buspirone and tandospirone and comparable to that o f diazepam. Similar results were also obtained with the water-lick con flict test in rats. The plasma concentration of MKC-242 in rats was mu ch higher than the reported value of buspirone during 0.25-6 hr after oral administration. In addition, MKC-242 reduced marble burying behav ior without reduction of motor activity. Fluoxetine, tandospirone and diazepam also reduced the behavior at non-sedative doses. These findin gs indicate that MKC-242 possesses a longer-lasting anxiolytic effect than azapirones. This might be due to the high concentration of the co mpound in plasma. In addition, it is also suggested that MKC-242 posse sses an antiobsessional effect.