Semi-synthesis of Novel Buprenorphine Derivatives and their Anti-nociceptive Properties and Dependency Potential

2021 ◽  
Author(s):  
Zahra Hasanpour ◽  
Peyman Salehi ◽  
Lennart Bunch ◽  
Mona Khoramjouy ◽  
Morteza Bararjanian ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Analgesic Effect ◽  
Preference Test ◽  
Biological Properties ◽  
Place Preference ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Active Compounds ◽  
Methyl Group ◽  
Analgesic Activities

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.

scholarly journals ASSESSMENT OF ANALGESIC ACTIVITY OF NELUMBO NUCIFERA FRUIT ETHANOL EXTRACT

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.

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

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.

Anti-Inflammatory, Antipyretic and Analgesic Potential of Zilla spinosa in Animal Model

2019 ◽  
Author(s):  
Riaz Ullah ◽  
Abdelaaty A Shahat ◽  
Ali S Alqahtani ◽  
Omer Mohammed Almarfad ◽  
Mohammad Sayer M Alharbi ◽  
...  
Keyword(s):  
Analgesic Activity ◽  
Tail Flick ◽  
Chloroform Fraction ◽  
Test Model ◽  
Hot Plate Test ◽  
Tail Flick Test ◽  
Antipyretic Activity ◽  
Rat Paw Edema ◽  
Anti Inflammatory ◽  
Analgesic Activities

The anti-inflammatory, antipyretic and analgesic activities of two concentrations (250 and 500 mg/kg) of the chloroform and butanol fractions of Zilla spinosa were determined. The carrageenan-induced rat paw edema assay was exercised for assessing the anti-inflammatory activity in rats, yeast-induced hyperthermia was utilized to assess the antipyretic activity in mice and the analgesic activity was measured by three different methods (hot-plate test model in mice, tail flick test in mice and acetic acid-induced writhing in mice). The antioxidant activity was studied by using the DPPH assay. The chloroform fraction of the methanol extract of Z. spinosa (ZSC) demonstrated the maximum inhibition of inflammation (50% at 500 mg/kg; 44% at 250 mg/kg). The chloroform fraction showed significant antipyretic activities (p andlt; 0.001 at 500 mg/kg) after 60 and 120 min of administration. ZSC also exhibited significant analgesic activity (p andlt;0.001). The butanol fraction (ZSB) was inactive in all the biological screening assays.

scholarly journals Heparin sensitization of fentanyl initiated mu-receptors

2021 ◽  
pp. 20-32
Author(s):  
А.Е. Khomutov ◽  
◽  
А.V. Deryugina ◽  
А.S. Lizunova ◽  
Z.V. Bobrova ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Anticoagulant Activity ◽  
Antinociceptive Effect ◽  
Regulatory Peptides ◽  
Tail Flick ◽  
Mu Opioid Receptors ◽  
Opioid Agonist ◽  
Hypotensive Action ◽  
Tail Flick Test ◽  
Mu Opioid

Heparin is an anticoagulant widely used in clinical practice. In addition to anticoagulant activity, heparin has a cytostatic, bacteriostatic, antilipemic, radioprotective effect, and exhibits antiallergic and hypotensive action. Heparin modulates cardiotropic, neurotropic, antihypoxic, anti-ischemic properties of regulatory peptides and pharmacological agents used in pain relief and anesthesia. At the same time, there is very little information about the antinociceptive effect of heparin. The aim of this work is to study the effect of heparin in combination with the opioid agonist fentanyl on mu-opioid receptors at the spinal and supraspinal levels. In experiments on laboratory rats, it was established that heparin, when pre-administered and combined with fentanyl, increases the latency in the tail flick test and the paw licking test. Naloxone, an opioid receptor antagonist, reduces antinociceptive efficacy of the studied compounds. Protamine sulfate also reduces the level of heparin sensitization of opioid receptors. Thus, the obtained data allow us to speak about the sensitizing effect of heparin on initiated by an agonist mu-opioid receptors at the spinal and supraspinal levels.

scholarly journals Synthesis and analgesic activities of some new 5-chloro-2(3H)-benzoxazolone derivatives

2017 ◽  
Vol 1 (3) ◽  
pp. 235-240 ◽  
Author(s):  
Yusuf Mulazim ◽  
Cevdet Berber ◽  
Hakkı Erdogan ◽  
Melike Hacer Ozkan ◽  
Banu Kesanli
Keyword(s):  
Biological Activities ◽  
Inflammatory Activity ◽  
Microwave Assisted Synthesis ◽  
Tail Flick ◽  
Synthesis Methods ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Tail Flick Test ◽  
Anti Inflammatory ◽  
Analgesic Activities

Abstract Affordable and practical synthesis methods in drug development have always been very attractive. Herein, microwave assisted synthesis was utilized to prepare piperazine substituted 5-chloro-2(3H)-benzoxazolone derivatives in 5 minutes. Structural characterization of these 5-chloro-2(3H)-benzoxazolone derivatives was achieved by IR, NMR, ESI-MS and elemental analysis. Since these types of compounds have been shown to have anti-inflammatory and analgesic activities there biological activities were also examined. Indomethacin (INDO) and acetylsalicylic acid (ASA) were used as reference. Carrageenan-induced hind paw edema in mice test was used to study anti-inflammatory activity. Compound 1 (100 mg / kg dose) showed the longest anti-inflammatory activity among the title compounds synthesized. For the analgesic activities, both hot-plate and tail-flick tests were employed. Compound 3 was found to have the highest activity in the hot-plate test whereas in the tail-flick test, compounds 1 and 2 showed higher anti-nociceptive activity.

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

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.

scholarly journals Analgesic Activities of Synthesized Divalent Metal Complexes of Tolfenamic Acid

2016 ◽  
Vol 15 (1) ◽  
pp. 89-96 ◽  
Author(s):  
Md Mahabob Ullah Mazumder ◽  
Abhijit Sukul ◽  
Sajal Kumar Saha
Keyword(s):  
Body Weight ◽  
Acetic Acid ◽  
Metal Complexes ◽  
Divalent Metal ◽  
Tolfenamic Acid ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Analgesic Activities ◽  
Divalent Metal Complexes ◽  
Analgesic Potency

The objective of the study was to synthesize and to uncover the potentially interesting biological peripheral and central analgesic activities of some new divalent metal complexes of tolfenamic acid. The inception of the study was carried out with the formation of complexes [Cu(tolf)2(H2O)]2, [Co(tolf)2(H2O)2] and [Zn(tolf)2(H2O)] through the reaction of tolfenamic acid, a potent anti-inflammatory drug, with Cu, Co and Zn salts. Characterization of the metal complexes of tolfenamic acid was furnished with spectral (FTIR, UV-Visible) and calorimetric (DSC) analysis. The peripheral analgesic activities of the complexes were investigated by acetic acid-induced writhing method. In peripheral analgesia model, Cu, Co and Zn complexes of tolfenamic acid showed significantly promising analgesic potency at a dose of 25 mg/kg body weight with percentage of inhibition of acetic acid induced writhing by 49.67% (p < 0.01), 67.32% (p < 0.001) and 72.55% (p < 0.001), respectively compared to the standard tolfenamic acid 46.41%. Radiant heat tail-flick test was used to observe the central analgesic activity which showed analgesic effect evidenced by % elongation time (34.59%, 25.34% and 53.08%), respectively compared to that of morphine 2 mg/kg body weight at an equimolar dose of tolfenamic acid at 10 mg/kg body weight after 30 minutes. In the final analysis, it can be stipulated that newly synthesized stable metal complexes of tolfenamic acid have promising pharmacological effects like peripheral and central analgesic potency. Therefore, these complexes may be the better therapeutic options in the near future however it needs further extensive analysis in the pharmacokinetics, pharmacodynamics and toxicology perspective.Dhaka Univ. J. Pharm. Sci. 15(1): 89-96, 2016 (June)

scholarly journals ASSESSMENT OF ANALGESIC ACTIVITY OF NELUMBO NUCIFERA FRUIT ETHANOL EXTRACT

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.

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

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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