The aim of the presented study was to examine the potential antinociceptive, antiedematous (anti-inflammatory), and antiallodynic activities of two 1H-pyrrolo[3,4-c]
pyridine-1,3(2H)-dione derivatives (DSZ 1 and DSZ 3) in various experimental models of
pain. For this purpose, the hot plate test, the
capsaicin test, the
formalin test, the
carrageenan model, and
oxaliplatin-induced
allodynia tests were performed. In the hot plate test, only DSZ 1 in the highest dose (20 mg/kg) was active but its effects appear to be due to sedatation rather than antinociceptiveness. In
capsaicin-induced neurogenic
pain model, both compounds displayed a significant antinociceptive activity. In the
formalin test, DSZ 1 and DSZ 3 (5-20 mg/kg) revealed antinociceptive activity in both phases but it was more pronounced in the second phase of the test. In this test, pretreatment with
caffeine,
DPCPX reversed the antinociceptive effect of DSZ 3. On the other hand, pretreatment with
L-NAME diminished the antinociceptive effect of DSZ 1. Pretreatment with
naloxone did not affect antinociceptive activity of both compounds. Similar to
ketoprofen, DSZ 1 and DSZ 3 showed antiedematous (antiinflammatory) and antihyperalgesic activity, and similar to
lidocaine local anesthetic activity. Furthermore, both compounds (5 and 10 mg/kg) reduced
tactile allodynia in acute and chronic phases of
neuropathic pain. In the in vitro studies, DSZ 1 and DSZ 3 reduced the COX-2 level in LPS-activated RAW 264.7 cells, which suggests their anti-inflammatory activity. In conclusion, both DSZ 1 and DSZ 3 displayed broad spectrum of activity in several
pain models, including neurogenic, tonic, inflammatory, and
chemotherapy-induced peripheral
neuropathic pain.