NOVEL BENZODIOXAN DERIVATIVE, ODIOXAN-2-YLMETHYL)AMINO]PROPOXY)-1,3-BENZODIOXOLE HCL (MKC-242), WITH ANXIOLYTIC-LIKE AND ANTIDEPRESSANT-LIKE EFFECTS IN ANIMAL-MODELS

Behavioral effects of MKC-242 odioxan-2-ylmethyl)amino]propoxy}-1,3-be nzodioxole HCl), a novel and selective serotonin IA receptor agonist, were investigated in rats and mice and compared against those of diaze pam, buspirone and tandospirone. MKC-242 (0.0625-0.25 mg/kg, p.o.) sig nificantly increased punished drinking in water-deprived rats. The ref erence compounds also increased punished drinking at doses of 10 to 40 mg/kg, p.o. The increase by MKC-242 was blocked by methoxyphenyl)pipe razin-1-yl)-2-phenylpropanamide, a serotonin 1A receptor antagonist. M KC-242 (0.1-0.5 mg/kg, p.o.) also increased social interaction under h igh light and unfamiliar conditions in rats. It had weak benzodiazepin e-like side effects in mice. MKC-242 (1, 3 mg/kg, p.o.) attenuated the reduction of locomotion caused by restraint stress in rats, the same effects were observed on both buspirone (100 mg/kg, p.o.) and tandospi rone (100 mg/kg, p.o.). In the forced swimming test in rats, MKC-242 ( 0.3-3 mg/kg, i.p.), 8-hydroxy-2-(di-n-propylamino)tetralin (1,3 mg/kg, i.p.) and amitriptyline (30 mg/kg, i.p.) reduced immobility, although diazepam, buspirone and tandospirone did not. The reduction by MKC-24 2 and 8-OH-DPAT was antagonized by methoxyphenyl)piperazin-1-yl)-2-phe nylpropanamide. Moreover, the reduction was also blocked by 1-(2-pyrim idinyl)piperazine (1-PP), a common metabolite of buspirone and tandosp irone. These findings suggest that MKC-242 possesses potent anxiolytic and antidepressant properties that are mediated via an activation of serotonin 1A receptors.