Antiallodynic activity of leflunomide is partially inhibited by naltrexone and glibenclamide and associated with reduced production of TNF-α and CXCL-1

Brito, Ana Mercy S.; Godin, Adriana M.; Augusto, Paulo Sérgio de Almeida; Menezes, Raquel R.; Melo, Ivo S.F.; Dutra, Marcela G.M.B.; Costa, Sarah O.A.M.; Goulart, Franciele A.; Rodrigues, Felipe F.; Morais, Marcela I.; Machado, Renes R.; Coelho, Márcio M.

doi:10.1016/j.ejphar.2017.10.026

Cited by 14 publications

(7 citation statements)

References 47 publications

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“…It has been reported that NTX administration reverses antinociceptive activity [31][32][33]. In relation to the effect of the pretreatment of mice with NTX, the results obtained in this study are not in agreement with those previously reported, since the synergistic nature of the effects of the combinations of NSAIDs were not reversed.…”

Section: Discussioncontrasting

confidence: 99%

Nitric Oxide and Opioids Involvement in Isobolographic Nsaids Antinociception

et al. 2019

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Different NSAIDs are used as antinociceptive in various analgesic assays, among which should be mentioned: ibuprofen, ketorolac , ketoprofen, meloxicam , paracetamol and others. It has been shown that NSAIDs possess antinociceptive activity by blocking cyclooxygenase enzymes (COXs). The present study was designed to evaluate the possible involvement of the nitridergic pathway due to L-NAME and the opioidergic route by NTX in the antinoception induced by NSAIDs using a murine pain model the tail flick test in an automatic tail flick algesiometer. The antinociception was evaluated by means of isobolographic analysis. The interaction between the combination of NSAIDs, via i.p., on basis of their ED25, demonstrated that the coadministration of the drugs were synergistic with the exception of the lack of effect in combination of meloxicam with ibuprofen and with ketorolac, since the result was additive. These data validate that the NSAIDs administered alone or in combinations produce antinociception in which other mechanisms of action must be added to the simple inhibition of COXs. In addition, the pretreatment of the mice with L-NAME and NTX does not change previous isobolographic parameters of the mixture of NSAIDs.

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Section: Discussioncontrasting

confidence: 99%

Nitric Oxide and Opioids Involvement in Isobolographic Nsaids Antinociception

et al. 2019

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“…Additionally, paclitaxel-induced peripheral neuropathy was attenuated by the selective Na v 1.7 and non-selective Na v 1.7-1.8 channel blockers ProTx II and ralfinamide, respectively (Li, North, et al, 2018; Liang, Yu, & Su, 2018). (Braga et al, 2019;Brito et al, 2018). These findings suggest that activators of Kv and K ATP channels might be effective alternatives to relief taxane-induced peripheral neuropathy.…”

Section: Sodium Channelsmentioning

confidence: 84%

“…For instance, H 2 S donors presented anti‐allodyinic activities in paclitaxel‐induced cold hypersensitivity in mice, a response that was attenuated by the Kv7 channel blocker XE991 (Di Cesare Mannelli et al, 2017). Additionally, the K ATP channel inhibitor glibenclamide reversed the antinociceptive actions of different compounds in paclitaxel‐induced peripheral neuropathy in mice (Braga et al, 2019; Brito et al, 2018). These findings suggest that activators of Kv and K ATP channels might be effective alternatives to relief taxane‐induced peripheral neuropathy.…”

Section: Taxane‐induced Peripheral Neuropathymentioning

confidence: 99%

Taxane‐induced neurotoxicity: Pathophysiology and therapeutic perspectives

Costa

Passos

Quintão

et al. 2020

British J Pharmacology

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Taxane-derived drugs are antineoplastic agents used for the treatment of highly common malignancies. Paclitaxel and docetaxel are the most commonly used taxanes; however, other drugs and formulations have been used, such as cabazitaxel and nabpaclitaxel. Taxane treatment is associated with neurotoxicity, a well-known and relevant side effect, very prevalent amongst patients undergoing chemotherapy. Painful peripheral neuropathy is the most dose-limiting side effect of taxanes, affecting up to 97% of paclitaxel-treated patients. Central neurotoxicity is an emerging side effect of taxanes and it is characterized by cognitive impairment and encephalopathy. Besides impairing compliance to chemotherapy treatment, taxane-induced neurotoxicity (TIN) can adversely affect the patient's life quality on a long-term basis. Despite the clinical relevance, not many reviews have comprehensively addressed taxaneinduced neurotoxicity when they are used therapeutically. This article provides an up-to-date review on the pathophysiology of TIN and the novel potential therapies to prevent or treat this side effect. Abbreviations: Ca v , voltage-gated calcium; CB 1 , cannabinoid receptor 1; CB 2 , cannabinoid receptor 2; CCL2, chemokine (C-C motif) ligand 2; CCR2, CC motif chemokine receptor 2; CIPN, chemotherapy-induced peripheral neuropathy; CREB, cAMP response element-binding; CX3CL1, C-X3-C motif chemokine ligand 1; CXCL1, C-X3-C motif chemokine ligand 1; CXCL12, C-X-C motif chemokine ligand 12; CXCR1, C-X-C motif chemokine receptor 1; CXCR2, C-X-C motif chemokine receptor 2; DRG, dorsal root ganglion; GHS-R, growth hormone secretagogue receptor; IENFs, intra-epidermal nerve fibres; K ATP , ATP-sensitive potassium channel; K v , voltage-gated potassium channel; mPTP, mitochondrial permeability transition pore; Na v , voltage-gated sodium channel; Nrf2, nuclear factor-2 erythroid-related factor-2; PIPN, paclitaxel-induced peripheral neuropathy; TICN, taxane-induced central neurotoxicity; TIN, taxane-induced neurotoxicity; TIPN, taxane-induced peripheral neuropathy; TLR4, toll-like receptor-4; TRPA1, transient receptor potential cation channel subfamily A member 1; TRPV1, transient receptor potential cation channel subfamily V member 1; TRPV4, transient receptor potential cation channel subfamily V member 4.

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“…The receiving solution was 0.01% phosphate buffer (pH 7.4) 17.8 mL and the effective osmotic area of the diffusion pool was 2.58 cm 2 . The receiver fluid was stirred with a magnetic rotor at a speed of 400 rpm and maintained at 37°C in order to keep the skin surface at 32°C 21) ; An amount of 3 mL of 0.1%TEF solution, 0.1%TEF emulsion and 0.1% (w/w) TEF microemulsion was placed into the donor compartment. Ensure that no air bubbles remained in the device.…”

Section: Stabilitymentioning

confidence: 99%

Development and Evaluation of a Water-in-oil Microemulsion Formulation for the Transdermal Drug Delivery of Teriflunomide (A771726)

Cao

Gao

Xia

et al. 2019

CHEMICAL & PHARMACEUTICAL BULLETIN

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Teriflunomide (TEF, A771726) is the active metabolite of leflunomide (LEF), a disease-modifying antirheumatic drug. The main purpose of this study was to develop and evaluate water-in-oil (W/O) microemulsion formulation of TEF. The W/O microemulsion was optimized formula is the physical and chemical stability of lecithin, ethanol, isopropyl myristate (IPM) and water (20.65/20.78/41.52/17.05 w/w) by using the pseudo-ternary phase diagram and the average droplet size is about 40 nm. The permeability of TEF microemulsion is about 6 times higher than control group in vitro penetration test. The results of antiinflammatory effect showed that compared with the control group, the external TEF microemulsion group could significantly inhibit swelling of paw in rats, and no significant difference compared with oral LEF group. The results of hepatotoxicity test show that there were normal content of alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and no obvious inflammatory infiltration of TEF microemulsion group compared with LEF group. The plasma concentration curve showed that compared with LEF group, the peak concentration of TEF microemulsion group was decreased, the half-life (t 1/2) was prolonged, and the relative bioavailability of TEF microemulsion was 75.35%. These results suggest that TEF W/O microemulsion can be used as a promising preparation to play an anti-inflammatory role while significantly reducing hepatotoxicity.

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Antiallodynic activity of leflunomide is partially inhibited by naltrexone and glibenclamide and associated with reduced production of TNF-α and CXCL-1

Cited by 14 publications

References 47 publications

Nitric Oxide and Opioids Involvement in Isobolographic Nsaids Antinociception

Nitric Oxide and Opioids Involvement in Isobolographic Nsaids Antinociception

Taxane‐induced neurotoxicity: Pathophysiology and therapeutic perspectives

Development and Evaluation of a Water-in-oil Microemulsion Formulation for the Transdermal Drug Delivery of Teriflunomide (A771726)

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