Antinociceptive effect of tadalafil in various pain models: Involvement of opioid receptors and nitric oxide cyclic GMP pathway

Mehanna, Mohammed M.; Domiati, Souraya; Chmaisse, Hania Nakkash; Mallah, Ahmed El

doi:10.1016/j.taap.2018.05.013

Cited by 27 publications

(33 citation statements)

References 19 publications

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“…In the present work, pretreatment of mice with LNAME resulted in a significant increase in the antinociceptive potency of each NSAID, reflected by a significant decrease in ED 50 , both in phase I and in phase II. This nociceptive increase is consistent with similar effects of LNAME in diazepam, clonazepam, chlordiazepoxide, tadalafil [18,19]. However, this nociceptive increase is not consistent with the decrease in the antinociception induced by LNAME in modafinil, ketamine, diclofenac, meloxicam and carbamazepine [19][20][21][22][23].…”

Section: Discussionmentioning

confidence: 59%

“…chlordiazepoxide and tapentadol analgesia [18,24]. However, the effect of produced by 7nitroindazole is not consistent with the reported for modafinil and dexmedetomidine [19,25]. The reasons for these discrepancies could be explained by the different strains of mice, the period of work of the protocol, the different doses used and others.…”

Section: Discussionmentioning

confidence: 98%

“…So, first the effectiveness of the nonselective inhibitor NOS, LNAME and the selective nNOS inhibitor, 7NI in increase the power of piroxicam, parecoxib, dexketoprofen and ketoprofen indicates that NO activity is involved in both phases of the hind paw formalin test. It is know, that after formalin administration, induces the release of substance P and glutamate and finally the release of NO that provokes central sensitization [19,24].Furthermore, studies with NOS inhibitors and cyclooxygenase inhibitor, suggest that NO stimulates the activity of COX. nNOS and LNAME has been involved in the spinal transmission of nociception in animal models of acute and chronic pain [7,11,13,14,26,27].…”

Section: Discussionmentioning

confidence: 99%

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Involvement of NO in Antinociception of NSAIDS in Murine Formalin Hind Paw Assay

et al. 2020

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There are different animal models to evaluate pain among them the formalin hind paw assay which is widely used since some of its events appear to be similar to the clinical pain of humans. The assay in which a dilute solution of formalin is injected into the dorsal hindpaw of a murine produces two ‘phases’ of pain behavior separated by a inactive period. The early phase (Phase I) is probably due to direct activation of nociceptors and the second phase (Phase II) is due to ongoing inflammatory input and central sensitization. Mice were used to determine the potency antinociceptive of piroxicam (1,3,10,and 30 mg/kg), parecoxib (0.3, 1,3,10 and 30 mg/kg), dexketoprofen (3,10,30 and 100 mg/kg) and ketoprofen (3,10,30 and 100 mg/kg). Dose-response for each NSAIDs were created before and after 5 mg/kg of L-NAME i.p. or 5 mg/kg i.p. of 7-nitroindazole. A least-squares linear regression analysis of the log dose–response curves allowed the calculation of the dose that produced 50% of antinociception (ED50) for each drug. The ED50 demonstrated the following rank order of potency, in the phase I: piroxicam > dexketoprofen > ketoprofen > parecoxib and in the phase II: piroxicam > ketoprofen > parecoxib > dexketoprofen. Pretreatment of the mice with L-NAME or 7-nitroindazol induced a significant increase of the analgesic power of the NSAIDs, with a significant reduction of the ED50. It is suggested that NO may be involved in both phases of the trial, which means that nitric oxide regulates the bioactivity of NSAIDs.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Involvement of NO in Antinociception of NSAIDS in Murine Formalin Hind Paw Assay

et al. 2020

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“…A hot plate test is used to check central pathways of the pain. Considering that APAP's analgesic effect is applied by central effects with little or almost no effect on the periphery, a hot plate test is frequently used for this purpose [24]. The non-nociceptive factors, such as weight, also influence paw withdrawal responses in the hot plate test.…”

Section: Discussionmentioning

confidence: 99%

N-acetylcysteine dose-dependently improves the analgesic effect of acetaminophen on the rat hot plate test

Nakhaee

Dastjerdi

Roumi

et al. 2021

BMC Pharmacol Toxicol

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Background Acetaminophen (APAP) induced hepatotoxicity is a clinically important problem. Up to now, interventive therapy with n-acetylcysteine (NAC) has been considered as a gold-standard treatment for APAP overdose. However, no study has focused on the efficacy of these drugs’ concurrent administration on probable enhancing therapeutic outcomes. Thus, this study was aimed to investigate the analgesic effect of co-administration of NAC and acetaminophen in male rats. The NAC-APAP drug formulation may demonstrate the stranger antinociceptive effect. Methods Forty-eight male Sprague-Dawley rats (12–14 weeks) randomly divided into six equal groups; control, APAP (received 300 mg/kg APAP), NAC (received 600 mg/kg NAC) and APAP+ NAC groups that received simultaneously 300 mg/kg APAP with 200–600 mg/kg NAC (AN200, AN400, AN600). All administrations were done orally for once. The antinociceptive effect was recorded by measurement of latency period on a hot plate in 30, 60, and 90 min after administrations. Results The results showed that NAC’s concurrent administration with APAP, dose-dependently increased APAP analgesic effects (p< 0.0001). Moreover, NAC treatment exhibited an antinociceptive effect in 60 and 90 min, per se. The treatments had no adverse effect on liver enzymes and oxidative stress. Conclusion Co-administration of NAC with APAP can improve the antinociceptive effect of APAP. It is suggested that this compound can enhance analgesic effects of APAP and eventually lead to a reduction in acetaminophen dose. Further studies are needed to evaluate the molecular mechanism of this hyper analgesic effect.

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“…13 In addition to the natural remedies, phosphodiesterase (PDE-5) inhibitors such as tadalafil, sildenafil, and vardenafil, based on their mechanism of action, can be employed in the treatment of other conditions than their urological use. 14,15 Kolawole and Francis proved that tadalafil had a dose-dependent ulcer reducing effect similar to that of cimetidine against indomethacin-induced ulcers in rats. 16 PDE-5 inhibitors prevent the hydrolytic degradation of cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP), which increases cGMP level and release of endogenous nitric oxide in the GIT promoting ulcer healing.…”

Section: Introductionmentioning

confidence: 98%

<p>Tadalafil-Loaded Limonene-Based Orodispersible Tablets: Formulation, in vitro Characterization and in vivo Appraisal of Gastroprotective Activity</p>

Mehanna¹,

Mneimneh²,

Domiati³

et al. 2020

IJN

Self Cite

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Background Gastric ulcer is a prevalent disease with various etiologies, including non-steroidal anti-inflammatory drugs and alcohol consumption. This study aimed to explore the dual gastric protection effect of tadalafil and limonene as a self-nanoemulsifying system (SNES)-based orodispersible tablets. Methods Tadalafil-loaded limonene-based SNES was prepared, and the optimum formula was characterized in terms of particle size (PS), polydispersity index (PDI), and zeta potential (ZP) then loaded on various porous carriers to formulate lyophilized orodispersible tablets (ODTs). The ODTs were evaluated via determining hardness, friability, content uniformity, wetting, and disintegration time. The selected ODT was examined for its gastric ulcer protective effect against alcohol-induced ulcers in rat model. Ulcer score and ulcer index were computed for rats stomachs that were inspected macroscopically and histopathologically. Results The prepared SNES had droplet size of 104 nm, polydispersity index of 0.2, and zeta potential of −15.4 mV. From the different ODTs formulated, the formula with superior wetting time: 23.67 s, outstanding disintegration time: 28 s, accepted hardness value: 3.11 kg/cm 2 and friability: 0.6% was designated. A significant gastroprotective effect of the unloaded and tadalafil-loaded ODTs was recognized compared to the omeprazole pre-treated group. Moreover, the histopathological analysis displayed very mild inflammation in the limonene-based ODTs group and intact structure in the tadalafil-loaded pre-treated animals. Conclusion Limonene gastroprotective effect functioned along with tadalafil in the form of SNES-incorporated ODTs could serve as a promising revenue for better efficacy in gastric ulcer prevention.

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Antinociceptive effect of tadalafil in various pain models: Involvement of opioid receptors and nitric oxide cyclic GMP pathway

Cited by 27 publications

References 19 publications

Involvement of NO in Antinociception of NSAIDS in Murine Formalin Hind Paw Assay

Involvement of NO in Antinociception of NSAIDS in Murine Formalin Hind Paw Assay

N-acetylcysteine dose-dependently improves the analgesic effect of acetaminophen on the rat hot plate test

<p>Tadalafil-Loaded Limonene-Based Orodispersible Tablets: Formulation, in vitro Characterization and in vivo Appraisal of Gastroprotective Activity</p>

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