Neuroprotective effects of ranolazine versus pioglitazone in experimental diabetic neuropathy: Targeting Nav1.7 channels and PPAR-γ

Elkholy, Shereen E.; Elaidy, Samah M.; El-Sherbeeny, Nagla A.; Toraih, Eman A.; El-Gawly, Hoda W.

doi:10.1016/j.lfs.2020.117557

Cited by 17 publications

(13 citation statements)

References 80 publications

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“…When acutely administered at higher doses (40mg/kg), serotonininduced scratching was also decreased by pioglitazone, suggesting its anti-scratching effects in mice. To some extent NO pathway as well as activation of PPAR-γ receptor initiate anti-scratching outcome of acute pioglitazone as reported by others (Elkholy et al, 2020). Results indicate that pioglitazone at does (2.5-10mg/kg) has quite opposing effects on serotonin and dopamine metabolism as compared to higher doses (30-40mg/kg).…”

Section: Discussionsupporting

confidence: 59%

Untitled

2021

Pak. J. Pharm. Sci

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Diabetics are twice as likely to have depression. It's normal to have long periods of sadness and anxiety. Pioglitazone has important role in the inflammatory response, which suggests that it might have the associated antidepressant effects being manifested by its anti-depressant profile which needs further exploration. Monitoring changes in behavioral and neurochemical profile of pioglitazone in a dose-dependent manner was the purpose of this study. Pioglitazone was injected to rats at the doses of 0mg/kg, 2.5mg/kg, 5mg/kg and 10mg/kg. Behavioral activities in open field, Skinner's box and elevated plus maze were monitored 20, 35 and 45 minutes respectively after pioglitazone injection. whole brain samples were collected following decapitation of rats one-hour after injection. Samples were kept at -70ºC till HPLC-EC analysis for neurochemical profile. Results show anxiogenic and sedative effects of pioglitazone at all three doses as indicated by Skinner's box, elevated plus maze activity and open field. Also there was an overall decreased dopamine metabolism and increased serotonin turnover. This suggests that diabetic patients using pioglitazone as a therapeutic option, may experience more potent effects of CNS depressants. Findings may help in extending therapeutics in diabetic patients suffering from anxiety and/or depression.

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Section: Discussionsupporting

confidence: 59%

Untitled

2021

Pak. J. Pharm. Sci

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“…It needs to be emphasized that ranolazine, an inhibitor of I Na(L) , has been demonstrated to be of benefit for peripheral or diabetic neuropathy [ 56 , 57 , 58 , 59 ]. This drug has also been revealed to have modifications on changes in peripheral nerve excitability [ 24 , 57 , 58 , 60 , 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

The Evidence for Effective Inhibition of INa Produced by Mirogabalin ((1R,5S,6S)-6-(aminomethyl)-3-ethyl-bicyclo [3.2.0] hept-3-ene-6-acetic acid), a Known Blocker of CaV Channels

Chuang

Cho

et al. 2022

IJMS

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Mirogabalin (MGB, Tarlige®), an inhibitor of the α2δ-1 subunit of voltage-gated Ca2+ (CaV) channels, is used as a way to alleviate peripheral neuropathic pain and diabetic neuropathy. However, to what extent MGB modifies the magnitude, gating, and/or hysteresis of various types of plasmalemmal ionic currents remains largely unexplored. In pituitary tumor (GH3) cells, we found that MGB was effective at suppressing the peak (transient, INa(T)) and sustained (late, INa(L)) components of the voltage-gated Na+ current (INa) in a concentration-dependent manner, with an effective IC50 of 19.5 and 7.3 μM, respectively, while the KD value calculated on the basis of minimum reaction scheme was 8.2 μM. The recovery of INa(T) inactivation slowed in the presence of MGB, although the overall current–voltage relation of INa(T) was unaltered; however, there was a leftward shift in the inactivation curve of the current. The magnitude of the window (INa(W)) or resurgent INa (INa(R)) evoked by the respective ascending or descending ramp pulse (Vramp) was reduced during cell exposure to MGB. MGB-induced attenuation in INa(W) or INa(R) was reversed by the further addition of tefluthrin, a pyrethroid insecticide known to stimulate INa. MGB also effectively lessened the strength of voltage-dependent hysteresis of persistent INa in response to the isosceles triangular Vramp. The cumulative inhibition of INa(T), evoked by pulse train stimulation, was enhanced in its presence. Taken together, in addition to the inhibition of CaV channels, the NaV channel attenuation produced by MGB might have an impact in its analgesic effects occurring in vivo.

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“…The explanation for such an effect could be that ranolazine, by blocking the Sodium channel, could reduce the IL-1β and TNF-α and then the IL1β expression. This experimental work showed that Ranolazine has neuroprotective effects comparable to pioglitazone [42]. Lastly, type 2 diabetes mellitus is an important risk factor for cognitive impairment [43].…”

Section: Diabetesmentioning

confidence: 64%

Through the heart and beyond: a review on ranolazine

Uran¹

2021

Monaldi Arch Chest Dis

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Ranolazine derives from piperazine and has been approved as a drug for the therapy of chronic stable angina. It acts by selectively inhibiting the late sodium inward current. Moreover, ranolazine has other metabolic features which makes it effective in other diseases as well as coronary artery ones. In this paper I make an updated review of all possible therapeutic roles of ranolazine: through cardiology and beyond.

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Neuroprotective effects of ranolazine versus pioglitazone in experimental diabetic neuropathy: Targeting Nav1.7 channels and PPAR-γ

Cited by 17 publications

References 80 publications

Untitled

Untitled

The Evidence for Effective Inhibition of INa Produced by Mirogabalin ((1R,5S,6S)-6-(aminomethyl)-3-ethyl-bicyclo [3.2.0] hept-3-ene-6-acetic acid), a Known Blocker of CaV Channels

Through the heart and beyond: a review on ranolazine

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