Abstract
The objective of our study was to evaluate the analgesic and anti-inflammatory activity, as well as possible organ toxicity of 2-3-3-methyl-pentanoic acid (compound 3d), a newly synthesized pyrrolic derivative, structurally similar to Celecoxib. Antinociception was assessed using animal pain models with thermal and chemical stimuli (paw withdrawal, tail-flick and formalin test). Anti-inflammatory activity was measured using the carrageenan-induced paw edema model. Blood samples were collected from the animals to study possible organ toxicity. All experiments were performed on male Wistar rats. The results in our study show that in experimental conditions 2-3-3-methyl-pentanoic acid has analgesic action against thermal and chemical stimuli. This effect is registered after both single and multiple administration of the compound. In the carrageenan model after single administration compound 3d did not inhibit formation of paw edema. After multiple administration all doses of compound 3d significantly suppressed paw edema at second, third and fourth hours. Hematological tests showed that compound 3d did not affect red blood cells and platelets but decreased white blood cell levels and the highest used dose decreased hemoglobin as well. Compound 3d decreased blood sugar levels and liver transaminases, compared to the control. Compound 3d did not affect creatinine levels but the smallest dose used lowered blood urea. We concluded antinociception in the tested compound is most likely mediated by supraspinal, spinal and peripheral mechanisms. Possible tolerance develops towards the analgesic action on spinal level after continuous administration. Anti-inflammatory activity, though significant, is probably not the leading cause for antinociception.
Highlights
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed medications, available as over -the-counter products.[1, 2] They are used in the treatment of both acute and chronic pain and inflammation.[3]
Selective cyclooxygenase-2 (COX-2) inhibitors were developed in the hope that aforementioned adverse drug reactions (ADRs) will be less severe and clinical studies do show reduced percentage of gastrointestinal tract (GIT) damage in patients, undergoing treatment with coxibs.[8]
Differences between metamizole sodium and compound 3d are not observed in this test
Summary
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed medications, available as over -the-counter products.[1, 2] They are used in the treatment of both acute and chronic pain and inflammation.[3] NSAIDs possess many adverse drug reactions (ADRs) – including bleeding from the upper gastrointestinal tract (GIT), damage to the liver and kidneys, allergies.[4, 5, 6, 7] Selective cyclooxygenase-2 (COX-2) inhibitors were developed in the hope that aforementioned ADRs will be less severe and clinical studies do show reduced percentage of GIT damage in patients, undergoing treatment with coxibs.[8] COX-2 inhibitors show various other ADRs, amongst which pro-thrombotic state and cardiotoxicity are the most serious.[9, 10]. A possible approach to the design and synthesis of novel drug molecules is based on using the chemical structure of an already existing medication as a prototype.[3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
