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Novel 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-d]pyridazinone Exert Antinociceptive Activity in the Tail-Flick and Formalin Test in Rodents and Reveal Reduced Gastrotoxicity
- Source :
- International Journal of Molecular Sciences, Volume 21, Issue 24, International Journal of Molecular Sciences, Vol 21, Iss 9685, p 9685 (2020)
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
Abstract
- Despite the availability of the current drug arsenal for pain management, there is still a clinical need to identify new, more effective, and safer analgesics. Based on our earlier study, newly synthesized 1,3,4-oxadiazole derivatives of pyrrolo[3,4-d]pyridazinone, especially 10b and 13b, seem to be promising as potential analgesics. The current study was designed to investigate whether novel derivatives attenuate nociceptive response in animals subjected to thermal or chemical noxious stimulus, and to compare this effect to reference drugs. The antinociceptive effect of novel compounds was studied using the tail-flick and formalin test. Pretreatment with novel compounds at all studied doses increased the latency time in the tail-flick test and decreased the licking time during the early phase of the formalin test. New derivatives given at the medium and high doses also reduced the late phase of the formalin test. The achieved results indicate that new derivatives dose-dependently attenuate nociceptive response in both models of pain and exert a lack of gastrotoxicity. Both studied compounds act more efficiently than indomethacin, but not morphine. Compound 13b at the high dose exerts the greatest antinociceptive effect. It may be due to the reduction of nociceptor sensitization via prostaglandin E2 and myeloperoxidase levels decrease.
- Subjects :
- Male
Nociception
0301 basic medicine
pyrrolo[3,4-d]pyridazinone
Pharmacology
Nociceptive Pain
lcsh:Chemistry
0302 clinical medicine
1,3,4-oxadiazole
pain
Prostaglandin E2
lcsh:QH301-705.5
Spectroscopy
Sensitization
Pain Measurement
Analgesics
Oxadiazoles
Chemistry
tail-flick test
General Medicine
Computer Science Applications
Pyridazines
medicine.anatomical_structure
Nociceptor
medicine.drug
Article
Dinoprostone
Catalysis
Inorganic Chemistry
03 medical and health sciences
formalin test
medicine
Noxious stimulus
Animals
Pyrroles
Rats, Wistar
Physical and Theoretical Chemistry
Molecular Biology
Peroxidase
Organic Chemistry
Rats
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Gastric Mucosa
Morphine
Licking
030217 neurology & neurosurgery
Tail flick test
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....c2f2d1bb1d874eb0961c64026a522a08
- Full Text :
- https://doi.org/10.3390/ijms21249685