Searching for Mechanisms of Analgesic Activity in the Group of 1H-Pyrrolo[3,4-c]pyridine-1,3(2H)-dione Derivatives—In Vitro and In Vivo Studies
Anna Dziubina, Dominika Szkatuła, Małgorzata Szafarz, Agata Siwek, Marek Kowalski, Joanna Gdula-Argasińska
TL;DR
This study evaluates two new compounds for their pain-relieving effects and mechanisms in both lab and animal models.
Contribution
The study introduces two novel 1H-pyrrolo[3,4-c]pyridine-1,3(2H)-dione derivatives with potential analgesic activity and explores their mechanisms.
Findings
DSZ-19 showed central/supraspinal analgesic activity without affecting movement.
Both compounds reduced tonic and neurogenic pain in formalin and capsaicin tests.
The compounds exhibited antiallodynic effects in neuropathy models and reduced inflammation.
Abstract
The present study was to evaluate the analgesic activity of two newly synthesized 1H-pyrrolo[3,4-c]pyridine-1,3(2H)-dione derivatives, designated DSZ-13 and DSZ-19. To achieve the desired result, the in vitro XTT cell proliferation assay, serotonin 5-HT1A receptor affinity and COX-1 and COX-2 enzyme inhibition potential of the compounds were conducted by real-time qPCR. Non-compartmental analysis was used to estimate the pharmacokinetic parameters of the compounds in serum and brain tissue. The analgesic activity was evaluated using various in vivo pain models, encompassing acute pain (hot plate test), tonic pain (formalin test), neurogenic pain (capsaicin test), carrageenan-induced acute inflammation, and neuropathic pain models. Both compounds showed moderate affinity for serotonin 5-HT1A receptors, a lack of cytotoxic activity, desirable pharmacokinetic parameters and slightly…
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Taxonomy
TopicsSynthesis and pharmacology of benzodiazepine derivatives · Synthesis and Reactivity of Heterocycles · Phosphodiesterase function and regulation