ArticleACS omega2022
Molecular Mechanics Simulations and Experimental Investigation of the Effect of Tadalafil on Various Inflammatory Pain Mediators.
Article in ACS omega, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 6 citations in OpenAlex.
- Fused Azine Derivatives Mitigate Long-Term Paracetamol-Induced Liver Fibrosis in Mice: Role of JNK1/ASK1 and Nrf2/HO-1 Signaling Pathways.Inflammation · 2026Article
- Tadalafil pretreatment attenuates doxorubicin-induced hepatorenal toxicity by modulating oxidative stress and inflammation in Wistar rats.Toxicology reports · 2024Article
- Indole-containing pharmaceuticals: targets, pharmacological activities, and SAR studies.RSC medicinal chemistry · 2024Review
- Structure Modification Converts the Hepatotoxic Tacrine into Novel Hepatoprotective Analogs.ACS omega · 2024Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTadalafil's exact analgesic mechanism is still unclear. The current study aimed to elucidate this mechanism in an inflammatory pain model.
methodsComputer-assisted simulation docking experiments were carried out to assess the binding of tadalafil to different ligands. The anti-inflammatory and analgesic effects of tadalafil were evaluated using formalin-induced paw edema and a von Frey filament test, respectively. The plantar paw of the mice was then dissected to quantify iNOS, nNOS, COX-2, TNFα, IL1, and IL10 gene expression levels using a real-time polymerase chain reaction. iNOS, TNFα, and COX-2 inhibition was reassessed in vitro using the ELISA technique. One-way analysis of variance followed by post hoc Tukey test or
resultsDocking analysis showed a superior binding score of tadalafil to COX-2, iNOS, IL-1, and TNF-α compared to that of indomethacin and morphine and a similar binding score to nNOS and IL-10 relative to that of indomethacin. In the in vivo study, tadalafil, after an hour of formalin administration, inhibited significantly paw edema, similar to indomethacin. Furthermore, it significantly increased the withdrawal force in the von Frey filament test as compared to the negative control, which was similar to the effect observed with indomethacin and morphine. The RT-PCR revealed that tadalafil reduced significantly the iNOS, COX-2, and TNF-α gene expressions but had no effect on nNOS, IL 1, and IL10. In vitro ELISA tests confirmed the inhibition of iNOS, COX-2, and TNF-α.
conclusionTadalafil probably exerts its analgesic effect through the simultaneous inhibition of iNOS, COX-2, and TNF-α, which is not the case with other nonsteroidal anti-inflammatory drugs. Nevertheless, further studies are required to confirm its mechanism.
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Registered trials
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