EFFECTS OF 2 N-ARYLPIPERAZINYLMETHYLPYRAZOLO [1,5-D][1,2,4]TRIAZINE DERIVATIVES IN PAIN AND ANTIDEPRESSANT TESTS IN MICE

The antinociceptive and antidepressant effects of two pyrazolotriazine erazin-1-yl)methyl-pyrazolo[1,5-d][1,2,4]-triazine (SM1) and dihydro- 4-oxo-5-[4-(4-fluorophenyl)piperazin-1-yl] methylpyrazolo[1,5-d][1,2,4 ] triazine (SM3) have been investigated in mice using classical pharma cological tests. The intraperitoneal LD50 values of SM1 and SM3 were 2 53.4 and 218.8 mgkg(-1) respectively. SMI and SM3 showed analgesic pro perties in the phenylbenzoquinone-induced abdominal constriction test (ED50 approximate to 10-15mgkg(-1), i.p.) and in the hat-plate test. T he antinociceptive effects of the triazines were significantly reduced by administration of naloxone (1 and 3.2mgkg(-1), s.c.) and yohimbine (1mgkg(-1), p.o.). Acute intraperitoneal administration of both compo unds (1 mgkg(-1) SM1 or 1.5 mgkg(-1)SM3) potentiated morphine (0.15mgk g(-1) s.c.) analgesia in the phenylbenzoquinone test. Although this sy nergistic activity was not reversed by methysergide (0.5mgkg(-1), i.p. ), the analgesic activity of both compounds was enhanced by administra tion of 5-hydroxytryptophan (50mgkg(-1) i.p.) in conjunction with carb idopa (25mgkg(-1) i.p.). Furthermore, neither compound (at 100mgkg(-1) , i.p.) significantly reduced the duration of immobility of mice in th e forced swimming test, and both (at 75 mgkg(-1), i.p.) were ineffecti ve at enhancing the toxic effects of yohimbine (30mgkg(-1), s.c.). Onl y SM3 (ED50=74.5mgkg(-1), i.p.) significantly antagonized reserpine (2 .5 mg kg(-1), i.p.)-induced ptosis. Thus, the results suggest that SMI and SM3 have antinociceptive properties related to co-involvement of opioidergic and alpha(2)-adrenoceptor mechanisms without associated an tidepressant properties.