Enhanced anxiolytic and analgesic effectiveness or a better safety profile of morphine and tramadol combination in cholestatic and addicted mice

Khakpai, Fatemeh; Issazadeh, Yasaman; Rezaei, Niloofar; Zarrindast, Mohammad‐Reza

doi:10.1097/wnr.0000000000001834

Cited by 3 publications

(2 citation statements)

References 62 publications

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“…Caspani et al . (2014), however, showed unaffected open arm time after tramadol administration to rats and Khakpai et al . (2022) did not observe a change in the test after tramadol and naloxone administration.…”

Section: Discussionmentioning

confidence: 95%

A novel tramadol–polycaprolactone implant could palliate heroin conditioned place preference and withdrawal in rats: behavioral and neurochemical study

Elshebiney,

Elgohary,

El-Shamarka

et al. 2024

Behavioural Pharmacology

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Drug dependence is a chronic brain disease characterized by craving and recurrent episodes of relapse. Tramadol HCl is a promising agent for withdrawal symptoms management, considering its relatively low abuse potential and safety. Oral administration, however, is not preferred in abstinence maintenance programs. Introducing an implantable, long-lasting formula is suggested to help outpatient abstinence programs achieve higher rates of treatment continuation. Tramadol implants (T350 and T650) were prepared on polycaprolactone polymer ribbons by the wet method. Male Wistar rats were adapted to heroin-conditioned place preference (CPP) at escalating doses (3–30 mg/kg, intraperitoneally, for 14 days). Implants were surgically implanted in the back skin of rats. After 14 days, the CPP score was recorded. Naloxone (1 mg/kg, intraperitoneally) was used to induce withdrawal on day 15, and symptoms were scored. Elevated plus maze and open field tests were performed for anxiety-related symptoms. Striata were analyzed for neurochemical changes reflected in dopamine, 3,4-dihydroxyphenyl acetic acid, gamma-aminobutyric acid, and serotonin levels. Brain oxidative changes including glutathione and lipid peroxides were assessed. The tramadol implants (T350 and T650) reduced heroin CPP and limited naloxone-induced withdrawal symptoms. The striata showed increased levels of 3,4-dihydroxyphenyl acetic acid, and serotonin and decreased levels of gamma-aminobutyric acid and dopamine after heroin withdrawal induction, which were reversed after implanting T350 and T650. Implants restore the brain oxidative state. Nonsignificant low naloxone-induced withdrawal score after the implant was used in naive subjects indicating low abuse potential of the implants. The presented tramadol implants were effective at diminishing heroin CPP and withdrawal in rats, suggesting further investigations for application in the management of opioid withdrawal.

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Section: Discussionmentioning

confidence: 95%

A novel tramadol–polycaprolactone implant could palliate heroin conditioned place preference and withdrawal in rats: behavioral and neurochemical study

Elshebiney,

Elgohary,

El-Shamarka

et al. 2024

Behavioural Pharmacology

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“…Cholestasis can impair social motivation behavior and induce depression-like behavior. Cholestasis can also affect anxiety and pain behaviors in mice 53 . Pharmacotherapy for neuropsychiatric disorders, such as anxiety and depression, has been characterized by significant interindividual variability in drug response and the development of side effects.…”

Section: Discussionmentioning

confidence: 99%

Systems biology approaches to identify potential targets and inhibitors of the intestinal microbiota to treat depression

Teng

Gao

et al. 2023

Sci Rep

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Depression is a common mental disease, with some patients exhibiting ideas and behaviors such as self-harm and suicide. The drugs currently used to treat depression have not achieved good results. It has been reported that metabolites produced by intestinal microbiota affect the development of depression. In this study, core targets and core compounds were screened by specific algorithms in the database, and three-dimensional structures of these compounds and proteins were simulated by molecular docking and molecular dynamics software to further study the influence of intestinal microbiota metabolites on the pathogenesis of depression. By analyzing the RMSD gyration radius and RMSF, it was finally determined that NR1H4 had the best binding effect with genistein. Finally, according to Lipinski's five rules, equol, genistein, quercetin and glycocholic acid were identified as effective drugs for the treatment of depression. In conclusion, the intestinal microbiota can affect the development of depression through the metabolites equol, genistein and quercetin, which act on the critical targets of DPP4, CYP3A4, EP300, MGAM and NR1H4.

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Endogenous opiates and behavior: 2022

Bodnar

2023

Peptides

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Enhanced anxiolytic and analgesic effectiveness or a better safety profile of morphine and tramadol combination in cholestatic and addicted mice

Cited by 3 publications

References 62 publications

A novel tramadol–polycaprolactone implant could palliate heroin conditioned place preference and withdrawal in rats: behavioral and neurochemical study

A novel tramadol–polycaprolactone implant could palliate heroin conditioned place preference and withdrawal in rats: behavioral and neurochemical study

Systems biology approaches to identify potential targets and inhibitors of the intestinal microbiota to treat depression

Endogenous opiates and behavior: 2022

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