Co-administration of Nimodipine with Morphine in Rat, delayed the development of tolerance to analgesic effect of Morphine: The Tail-Flick test study: New insight for treatment of chronic pain

Abstract: Novel 1,2,3-triazole-tethered N-norbuprenorphine derivatives with an OMe or OH group at the C3 position were synthesized alongside with evaluation of their analgesic properties. The analgesic activities of the resulting library were investigated via tail flick test in mice. Our results indicated that 10b and 10e were as effective as the starting compounds 8 and 9 with ED50 equal to 16.59 and 19.44 mg/kg, respectively. To investigate the effect of a methyl group at C3 on biological properties, the most active compounds were O-demethylated and their anti-nociceptive effects were assessed. The new O-demethylated derivatives (11b and 11e) showed better analgesic properties than the parent compounds with ED50 of 14.73 and 15.80 mg/kg, respectively. Naloxone prevented the analgesic effect of the synthesized compounds, indicating that the opioid receptors are highly involved in the anti-nociceptive effects of these. The potential dependency effects of the most potent derivatives were studied by condition place preference test in mice and compared to morphine and buprenorphine. Interestingly, 10b, 10e, 11b, and 11e did not show any dependency effect, similar to buprenorphine.

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ASSESSMENT OF ANALGESIC ACTIVITY OF NELUMBO NUCIFERA FRUIT ETHANOL EXTRACT

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2019v11i11.35455 ◽

2019 ◽

pp. 1-5

Author(s):

MUHAMMAD ALI RAJPUT ◽

TABASSUM ZEHRA ◽

FIZZAH ALI ◽

GUNESH KUMAR

Keyword(s):

Analgesic Activity ◽

Analgesic Effect ◽

Research Work ◽

Ethanol Extract ◽

Nelumbo Nucifera ◽

Herbal Remedies ◽

Tail Flick ◽

Traditional Use ◽

Tail Flick Test ◽

Pathway Inhibition

Objective: Utilization of herbal remedies rich in flavonoids and vitamins have increased significantly these days to treat various disorders, thus existing research work encircled to appraise the analgesic effect of Nelumbo nucifera fruit (NNF) for evaluating its traditional use pharmacologically in disorders which are associated with pain and inflammation. Methods: Central analgesic activity in mice was assessed by tail flick test and the latency time i.e. the removal of tail from the stimulus was recorded. Similarly acetic acid induced writhing test was also conducted for the assessment of peripheral analgesic effect in mice and number of writhes was counted along with percent inhibition of writhes. Results: In tail flick test the peek anti-nociceptive effect at all doses of fruit was observed at 90 min. However, the percentage of tail elongation time was highest at a dose of 200 mg/kg i.e. 82% at 90 min. Number of writhes was highly significantly reduced at all doses of NNF but maximum effects were observed at dose 200 mg/kg as compared to control, indicating 48.41 % inhibition of writhes. Conclusion: NNF have exhibited strong analgesic effect in both animal models, which may be connected with the synergistic actions of flavonoids, saponins and tannins on arachidonic acid pathway inhibition. Hence NNF seems to have a great potential in disorders associated with pain but more experimental trials in this field are required to confirm these findings.

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EFFECTIVENESS PROGNOSTICATION OF A COMBINED ANALGESIC FORMULATION DEPENDING ON QUANTITATIVE COMPOSITION OF ITS COMPONENTS

Токсикологический вестник ◽

10.36946/0869-7922-2016-5-44-48 ◽

2016 ◽

pp. 44-48

Author(s):

N. G. Vengerovich ◽

M. A. Yudin ◽

A. S. Nikiforov ◽

G. S. Sagalov ◽

M. S. Vakhviyainen ◽

...

Keyword(s):

Drug Interaction ◽

Opioid Receptor ◽

Analgesic Activity ◽

Analgesic Effect ◽

Receptor Agonist ◽

Quantitative Composition ◽

Tail Flick ◽

Tail Flick Test ◽

Opioid Receptor Agonist ◽

Combined Administration

In experiments on rats, analgesic activity of fentanyl opioid receptor agonist and central 2-adrenomimetic dexmedetomidine as well as the character of their interaction at a combined administration were studied. Meaneffective anesthetic doses of the drugs in heat radiant tail flick test were 54.5 and 22.5 μg/kg correspondingly. Using izobolographic analysis, it was shown that for a combination with equal parts or with a greater part of fentanyl, the type of drug interaction can be characterized as potentiation. A model of prognostication of probability values of the analgesic effect development in relation to doses of combination components was elaborated and experimentally tested.

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Effect of adjuvant drugs on the analgesic activity of opioid morphine analgesics and compound RU-1205

Research Results in Pharmacology ◽

10.3897/rrpharmacology.7.68025 ◽

2021 ◽

Vol 7 (3) ◽

pp. 41-47

Author(s):

Alexander A. Spasov ◽

Olesya Iu. Grechko ◽

Natalya V. Eliseeva ◽

Yuliya V. Lifanova ◽

Angelina N. Aleksandrenkova

Keyword(s):

Analgesic Activity ◽

Analgesic Effect ◽

Opioid Analgesics ◽

Benzodiazepine Receptor ◽

Tail Flick ◽

Opioid Agonist ◽

Tail Flick Test ◽

Kappa Agonist ◽

Kappa Opioid Agonist ◽

Probable Interaction

Introduction: Adjuvant medications can be used to increase the analgesic effect of opioid analgesics, reduce the manifestation of side effects, and also for premedication. This paper provides information on the effect of clonidine, haloperidol, metocloparmide, diazepam, midazolam on opioid analgesics: - morphine and the selective kappa-opioid agonist compound RU-1205. Materials and methods: A probable interaction between RU-1205, morphine and adjuvant drugs in pain behaviors was carried out on the model of somatogenic pain. 95 male mice received either RU-1205 (5 mg/kg, i.p.) and morphine (1 mg/kg, i.p.) separately or in combination with haloperidol (0.45 mg/kg, i.p.); midazolam (0.3 mg/kg, i.p.); diazepam (1 mg/kg, i.p.); metoclopramide (5 mg/kg, i.p.), and clonidine (1 mg/kg, i.p.). The analgesic effect was assessed by tail flick test. Registration of the latent period of the reaction was carried out 30, 60 and 90 minutes after the adjuvant drug administration. Results: When studying the interaction with morphine, it was found that clonidine, haloperidol and metoclopramide enhanced the effects; diazepam offset them, and midazolam had no affect on the analgesic properties. In the course of the studies, RU-1205 showed an increase in analgesic activity when combined with clonidine, a slight increase with midazolam, and a decrease when co-administered with diazepam. Haloperidol had no influence on the effect of RU-1205, while metoclopramide both potentiated and reduced the analgesic effect. Discussion: Pharmacodynamic and pharmacokinetic interactions of RU-1205 with an α2AR agonist, benzodiazepine receptor agonists, D2P antagonist, and σ-receptor blocker were established. Conclusion: The presented data make it possible to more accurately formulate ideas about the localization and action mechanism of the kappa-agonist of opioid receptors, the compound RU-1205.

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ASSESSMENT OF ANALGESIC ACTIVITY OF NELUMBO NUCIFERA FRUIT ETHANOL EXTRACT

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2019.35455 ◽

2019 ◽

pp. 1-5

Author(s):

MUHAMMAD ALI RAJPUT ◽

TABASSUM ZEHRA ◽

FIZZAH ALI ◽

GUNESH KUMAR

Keyword(s):

Analgesic Activity ◽

Analgesic Effect ◽

Research Work ◽

Ethanol Extract ◽

Nelumbo Nucifera ◽

Herbal Remedies ◽

Tail Flick ◽

Traditional Use ◽

Tail Flick Test ◽

Pathway Inhibition

Objective: Utilization of herbal remedies rich in flavonoids and vitamins have increased significantly these days to treat various disorders, thus existing research work encircled to appraise the analgesic effect of Nelumbo nucifera fruit (NNF) for evaluating its traditional use pharmacologically in disorders which are associated with pain and inflammation. Methods: Central analgesic activity in mice was assessed by tail flick test and the latency time i.e. the removal of tail from the stimulus was recorded. Similarly acetic acid induced writhing test was also conducted for the assessment of peripheral analgesic effect in mice and number of writhes was counted along with percent inhibition of writhes. Results: In tail flick test the peek anti-nociceptive effect at all doses of fruit was observed at 90 min. However, the percentage of tail elongation time was highest at a dose of 200 mg/kg i.e. 82% at 90 min. Number of writhes was highly significantly reduced at all doses of NNF but maximum effects were observed at dose 200 mg/kg as compared to control, indicating 48.41 % inhibition of writhes. Conclusion: NNF have exhibited strong analgesic effect in both animal models, which may be connected with the synergistic actions of flavonoids, saponins and tannins on arachidonic acid pathway inhibition. Hence NNF seems to have a great potential in disorders associated with pain but more experimental trials in this field are required to confirm these findings.

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Effect of Hydroalcoholic Extract of Hyssop on Acute Pain in Male Rats Using Tail Flick Test

Avicenna Journal of Pharmaceutical Research ◽

10.34172/ajpr.2021.03 ◽

2021 ◽

Vol 2 (1) ◽

pp. 15-19

Author(s):

Amir Larki-Harchegani ◽

Abbas Ehsanikia ◽

Sara Ataei ◽

Fakhriosadat Hosseini ◽

Rasool Haddadi

Keyword(s):

Analgesic Effect ◽

Positive Control ◽

Male Rats ◽

Saline Control ◽

Control Group ◽

Tail Flick ◽

Tail Flick Test ◽

Hydroalcoholic Extract ◽

Analgesic Effects ◽

Iranian Traditional Medicine

Background: Iranian traditional medicine uses hyssop (Hyssopus officinalis) as an effective medicinal plant to reduce pain and inflammation in different diseases. Although the anti-inflammatory effect of this plant is proved, there is no study into its analgesic effects. Thus, this study aimed to investigate the analgesic effect of the hydroalcoholic extract from hyssop flowers and upper branches. Methods: This experimental study was conducted on 66 male rats that were divided into several groups including a saline control group, the groups of different doses of hyssop extract, morphine positive control group, the groups of hyssop extract plus morphine, and the most effective dose of the hyssop extract plus naloxone. All injections were administered intraperitoneally, and the pain was measured through the tail flick test. Results: Based on the results, 600 mg/kg was the most effective analgesic hyssop extract dose, and the most analgesic effect was observed at 45 minutes after administration. In addition, the administration of the most effective extract dose (600 mg/kg) plus morphine significantly improved the analgesic effects of morphine (P<0.001). Finally, the administration of naloxone plus the most effective extract dose (600 mg/kg) significantly reduced the analgesic effect of the extract (P<0.05). Conclusion: Overall, the hydroalcoholic extract of hyssop has analgesic effects that are probably applied through opioid receptors.

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AN AN STUDY OF ANALGESIC ACTIVITY OF HAFFNER’S TAIL CLIP METHOD ON ALBINO WISTAR RATS OF SOME POLYHERBAL FORMULATION

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i9.34561 ◽

2019 ◽

pp. 142-144

Author(s):

LOKENDRA SINGH

Keyword(s):

Analgesic Activity ◽

Side Effect ◽

Analgesic Effect ◽

Design Method ◽

Curcuma Longa ◽

Albino Rats ◽

Tail Flick ◽

Herbal Drugs ◽

Tail Flick Test ◽

Tail Clip

Objective: Herbal drugs are more beneficial better than aspirin because this is an herb so no side effect this drug and it is easy to collect or use to as herbal drugs. Words are inadequate to describe the motivation for my work given to my beloved guide. I would like to add special thanks to my guide Gauravbilwal, for their guidance, support, and encouragement. Purpose (Hypothesis): The main purpose of this article pays to attention for herbal drugs because they are naturally old effective drugs. As well as, Ayurveda treatment is very older effective technique. Design/Method: Haffner gave to this technique of determining analgesic are around in 1929. Procedure: This technique according to tail if clipped with any object and tightly or will be compression generation of pain in the tail as well as mice starting to bite that portion of its tail, and could evaluate and recorded the response how much it bites tail quickly or in potential. Using this simple yet important marvel, we may apply the drug to be evaluated and record the response whether it bites tail quickly or in potential. If given drugs have analgesic likely, then rat will not bite its tail so frequently. Mice that do not show any response within 15 s will reject from the experiment. Results: The found in analgesic activity of additional compounds test to significant on tail flick test than acetic acid-induced test and thus it appears that the test compounds inhibit predominantly the peripheral pain mechanism. The results of the study indicate that the extracts of polyherbal plants of analgesic activity by reducing the abdominal constriction significantly and may supposed to have a possible role in inhibition of cyclooxygenase in the prostaglandin pathways (p****<0.0001, ***0.0001, *0.05). Conclusion: The present study showed the significant analgesic effect of both aqueous and alcoholic at 400 mg/kg doses in albino rats, we reported for the 1st time analgesic effect of different plants (Curcuma longa, Colchicaceae, Colocynthis, Withania somnifera, and Achyranthes aspera) in Haffner’s tail clip models. Aspirin has each uncoated effervescent tablet content are acetylsalicylic acid I.P. 325 mg. Finally summarized in this article represent a most effective results of herbal drugs equalized allopathic drugs without any other side effect. Hence, this is very usefully combination of Ayurveda drugs.

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Comparative evaluation of phasic and chemical antinociceptive action of a conventional and a novel anticonvulsants in experimental models of tail flick and formalin test

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20190328 ◽

2019 ◽

Vol 7 (2) ◽

pp. 323

Author(s):

Saurabh Kansal ◽

Rohan Sirohi ◽

Ruchika Agarwal

Keyword(s):

Analgesic Effect ◽

Formalin Test ◽

Opioid Analgesic ◽

Late Phase ◽

Antinociceptive Effect ◽

Experimental Models ◽

Phase Response ◽

Tail Flick ◽

Second Phase ◽

Tail Flick Test

Background: Some antiepileptic drugs have been shown to be clinically efficacious in treatment of neuropathic pain and are being used by clinician.Methods: This study determined the analgesic effect of gabapentin (a conventional anticonvulsant) and levitiracetam (a novel anticonvulsant) in rats in different types of acute and chronic nociceptive test like tail flick and formalin test and compared its potency with a conventional non opioid analgesic diclofenac.Results: Per oral administration of gabapentin produced no any marked effect on early phase response of formalin test but significantly suppressed the late phase response while levitiracetam produced no any type of significant effect in both phases. In tail flick test gabapentin as well as levitiracetam produced no any significant analgesic effect while diclofenac produced significant reduction of pain in tail flick test as well as in both phases of formalin test.Conclusions: Thus, we have observed that gabapentin produced antinociception in chronic pain as second phase of formalin test reflects chronic inflammatory pain while levitiracetam did not produce any type of antinociceptive effect as it could not suppress the pain significantly in both tail flick and formalin test.

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Ketamine Attenuates and Reverses Morphine Tolerance in Rodents

Anesthesiology ◽

10.1097/00000542-199612000-00017 ◽

1996 ◽

Vol 85 (6) ◽

pp. 1357-1366. ◽

Cited By ~ 85

Author(s):

Naohito Shimoyama ◽

Megumi Shimoyama ◽

Charles E. Inturrisi ◽

Kathryn J. Elliott

Keyword(s):

Morphine Tolerance ◽

Fold Increase ◽

Response Analysis ◽

Tail Flick ◽

Tail Flick Test ◽

Aspartate Receptor ◽

Tenfold Increase ◽

Reverse Tolerance ◽

Before And After ◽

Development Of Tolerance

Background The development of tolerance complicates the use of morphine to manage persistent pain. N-methyl-D-aspartate receptor antagonists can attenuate or reverse morphine tolerance. The authors studied ketamine's ability to modulate morphine tolerance. Method Tolerance was produced in mice given morphine subcutaneously and was assessed by a cumulative dose-response analysis using the tail-flick test. The ability of ketamine at 0.3, 3, or 10 mg/kg given subcutaneously before and after morphine to attenuate the development of tolerance was assessed. The ability of 10 mg/kg ketamine to reverse tolerance produced by the subcutaneous implantation of morphine pellets to mice was also assessed. Rats were made tolerant to intraspinal morphine and the effects of the coadministration of 12 micrograms intraspinal ketamine were assessed. Results Morphine given subcutaneously produced a fivefold increase in the median effective (ED50) dose of morphine, which was dose-dependently attenuated by subcutaneously administered ketamine. A tenfold increase in the morphine ED50 produced by morphine pellets was completely reversed by ketamine given subcutaneously. Intraspinal morphine produced a 46-fold increase in its ED50, which was almost completely attenuated by the coadministration of intraspinal ketamine. Conclusions Systemically administered ketamine attenuates and reverses systemically induced morphine tolerance in mice, and intraspinal ketamine attenuates tolerance produced by intraspinal morphine in rats.

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