Similarity and dissimilarity in antinociceptive effects of dipeptidyl-peptidase 4 inhibitors, Diprotin A and vildagliptin in rat inflammatory pain models following spinal administration

Balogh, Mihály; Varga, B; Karádi, Dávid Árpád; Riba, Pál; Puskár, Zita; Kozsurek, Márk; Al-Khrasani, Mahmoud; Király, Kornél

doi:10.1016/j.brainresbull.2019.02.001

Cited by 9 publications

(9 citation statements)

References 37 publications

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“…Similarly, Balogh et al, in their study on rat inflammatory pain models reported that the anti-hyperalgesic effect of DPP4 inhibitors can be attributed to the activation of endogenous opioid system especially the delta opioid receptor. 19 In our study, in addition to an increase in pain threshold and tolerance time, we also observed similar baseline values on day-1 and day-8 between the groups for pain threshold and pain tolerance time. Similar baselines values could due to the fact that GLP-1 concentrations are normal in the fasting state in healthy individuals, and increases only in response to high glucose levels after a meal.…”

Section: Discussionsupporting

confidence: 86%

Evaluation of the analgesic activity of single and multiple oral doses of teneligliptin (20 mg/day), using hot air analgesiometer in healthy human volunteers: a randomized, double blind, placebo controlled, cross over study

Butul

Pingali

Nutalapati

2020

Int J Basic Clin Pharmacol

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Background DPP-4inhibitors showed analgesic and anti-inflammatory activity in human and animal-studies. DPP-4 inhibitors improved nerve function and thermal nociception in animal models. Aim of the study was to explore analgesic activity of single and multiple doses of teneligliptin 20 mg/day using hot air analgesiometer in healthy human volunteers.Methods: After IEC approval and informed consent, subjects were randomized to receive either teneligliptin 20 mg or placebo in double-blinded manner with standard breakfast. Mean pain threshold and tolerance(sec) using hot air analgesiometer were recorded at baseline and 1 hr, 2 hrs post drug on day1, for single dose study. Subsequently drugs were administered under supervision daily for 6 days and same procedure repeated on day8 for multiple-dose study. After 2 weeks washout, subjects crossed over in period 2 to other formulation and same procedure repeated to determine study parameters. Fasting blood-sugar (FBS) monitored, ADRs recorded in CRF. Statistical analysis done with SPSS20.0.Results: Twelve-healthy subjects (8 males, 4 females) with mean age 33.08±4.69 years, mean BMI 22.6±1.37kg/m2 participated. Single dose teneligliptin produced significant increase in pain threshold (35.9%) and pain tolerance (25.1%) (p<0.0001) at 1hour compared to baseline. With multiple doses, pain threshold increased by 37.1% and pain tolerance by 25.4% (p<0.0001) at 1hour compared to baseline. The increase in pain threshold and tolerance values at 1 and 2 hours were similar. There was no significant change in pain threshold(p=0.4135) and tolerance (p=0.4476) at baseline on day1 and day 8. Placebo showed non-significant change in study parameters. Both treatments well tolerated. FBS of volunteers within normal limits during treatment period and no hypoglycemia reported.Conclusions: Results of our study suggest that teneligliptin20mg in healthy subjects demonstrated significant analgesic activity on day 1 and day 8 compared to baseline & placebo. Its role in painful diabetic conditions can be further explored.

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Section: Discussionsupporting

confidence: 86%

Evaluation of the analgesic activity of single and multiple oral doses of teneligliptin (20 mg/day), using hot air analgesiometer in healthy human volunteers: a randomized, double blind, placebo controlled, cross over study

Butul

Pingali

Nutalapati

2020

Int J Basic Clin Pharmacol

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“…For the induction of mononeuropathic pain in rats of 100–150 g, pSNL was applied, based on the Seltzer method [ 27 , 40 ]. In short, rats were anesthetized with 60 mg/kg intraperitoneal pentobarbital (2.5 mL/kg volume) and were put on a pillow of 30 °C.…”

Section: Methodsmentioning

confidence: 99%

The Acute Antiallodynic Effect of Tolperisone in Rat Neuropathic Pain and Evaluation of Its Mechanism of Action

Lakatos

Karádi

Galambos

et al. 2022

IJMS

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Current treatment approaches to manage neuropathic pain have a slow onset and their use is largely hampered by side-effects, thus there is a significant need for finding new medications. Tolperisone, a centrally acting muscle relaxant with a favorable side effect profile, has been reported to affect ion channels, which are targets for current first-line medications in neuropathic pain. Our aim was to explore its antinociceptive potency in rats developing neuropathic pain evoked by partial sciatic nerve ligation and the mechanisms involved. Acute oral tolperisone restores both the decreased paw pressure threshold and the elevated glutamate level in cerebrospinal fluid in neuropathic rats. These effects were comparable to those of pregabalin, a first-line medication in neuropathy. Tolperisone also inhibits release of glutamate from rat brain synaptosomes primarily by blockade of voltage-dependent sodium channels, although inhibition of calcium channels may also be involved at higher concentrations. However, pregabalin fails to affect glutamate release under our present conditions, indicating a different mechanism of action. These results lay the foundation of the avenue for repurposing tolperisone as an analgesic drug to relieve neuropathic pain.

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“…This consisted of placing the animals in the plastic cages of the experimental apparatus once daily. Mechanical allodynia induced by neuropathy was assessed using a dynamic plantar esthesiometer (DPA 37450, Ugo Basile, Italy) as described before [56,65] with the following settings: incrementation: 10 g/s, maximal force: 50 g. The PWTs of animals were measured in grams, following at least five minutes of habituation in the cage in the case of each animal. Each paw was measured three times and the means of the three measurements were used for further analysis.…”

Section: Experimental Protocols 431 Mononeuropathic Pain Modelmentioning

confidence: 99%

Telmisartan Is a Promising Agent for Managing Neuropathic Pain and Delaying Opioid Analgesic Tolerance in Rats

Karádi

Galambos

Lakatos

et al. 2023

IJMS

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Despite the large arsenal of analgesic medications, neuropathic pain (NP) management is not solved yet. Angiotensin II receptor type 1 (AT1) has been identified as a potential target in NP therapy. Here, we investigate the antiallodynic effect of AT1 blockers telmisartan and losartan, and particularly their combination with morphine on rat mononeuropathic pain following acute or chronic oral administration. The impact of telmisartan on morphine analgesic tolerance was also assessed using the rat tail-flick assay. Morphine potency and efficacy in spinal cord samples of treated neuropathic animals were assessed by [35S]GTPγS-binding assay. Finally, the glutamate content of the cerebrospinal fluid (CSF) was measured by capillary electrophoresis. Oral telmisartan or losartan in higher doses showed an acute antiallodynic effect. In the chronic treatment study, the combination of subanalgesic doses of telmisartan and morphine ameliorated allodynia and resulted in a leftward shift in the dose–response curve of morphine in the [35S]GTPγS binding assay and increased CSF glutamate content. Telmisartan delayed morphine analgesic-tolerance development. Our study has identified a promising combination therapy composed of telmisartan and morphine for NP and opioid tolerance. Since telmisartan is an inhibitor of AT1 and activator of PPAR-γ, future studies are needed to analyze the effect of each component.

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Similarity and dissimilarity in antinociceptive effects of dipeptidyl-peptidase 4 inhibitors, Diprotin A and vildagliptin in rat inflammatory pain models following spinal administration

Cited by 9 publications

References 37 publications

Evaluation of the analgesic activity of single and multiple oral doses of teneligliptin (20 mg/day), using hot air analgesiometer in healthy human volunteers: a randomized, double blind, placebo controlled, cross over study

Evaluation of the analgesic activity of single and multiple oral doses of teneligliptin (20 mg/day), using hot air analgesiometer in healthy human volunteers: a randomized, double blind, placebo controlled, cross over study

The Acute Antiallodynic Effect of Tolperisone in Rat Neuropathic Pain and Evaluation of Its Mechanism of Action

Telmisartan Is a Promising Agent for Managing Neuropathic Pain and Delaying Opioid Analgesic Tolerance in Rats

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