Antinociceptive Effects of Aza-Bicyclic Isoxazoline-Acylhydrazone Derivatives in Different Models of Nociception in Mice

2022 ◽  
Vol 22 ◽  
Author(s):  
Fernanda Virginia Barreto Mota ◽  
Felipe Neves Coutinho ◽  
Vanessa Mylenna Florêncio de Carvalho ◽  
Julyanne Cunha de Assis Correia ◽  
Isla Vanessa Gomes Alves Bastos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acetic Acid ◽  
Potassium Channels ◽  
Antinociceptive Activity ◽  
Writhing Test ◽  
Cholinergic Pathways ◽  
Chemical Models ◽  
Pain Models ◽  
Antinociceptive Effects ◽  
Adrenergic Systems

Background: In a study recently published by our research group, the compounds isoxazoline-acylhydrazone derivatives R-99 and R-123 presented promising antinociceptive activity. However, the mechanism of action of this compound is still unknown. Objective: This study aimed to assess the mechanisms involved in the antinociceptive activity of these compounds in chemical models of pain. Methods: Animals were orally pretreated and evaluated in the acetic acid-, formalin-, capsaicin-, carrageenan- and Complete Freund's Adjuvant (CFA)-induced pain models in mice. The effects of the compounds after pretreatment with naloxone, prazosin, yohimbine, atropine, L-arginine, or glibenclamide were studied, using the acetic acid-induced writhing test to verify the possible involvement of opioid, α1-adrenergic, α2-adrenergic or cholinergic receptors, and nitric oxide or potassium channels pathways, respectively. Results: R-99 and R-123 compounds showed significant antinociceptive activity on pain models induced by acetic acid, formalin, and capsaicin. Both compounds decreased the mechanical hyperalgesia induced by carrageenan or CFA in mice. The antinociceptive effects of R-99 and R-123 on the acetic acid-induced writhing test were significantly attenuated by pretreatment with naloxone, yohimbine or atropine. R-99 also showed an attenuated response after pretreatment with atropine and glibenclamide. However, on the pretreatment with prazosin, there was no change in the animals' response to both compounds. Conclusion: R-99 and R-123 showed antinociceptive effects related to mechanisms that involve, at least in part, interaction with the opioid and adrenergic systems and TRPV1 pathways. The compound R-99 also interacts with the cholinergic pathways and potassium channels.

scholarly journals Perillyl Alcohol: Antinociceptive Effects and Histopathological Analysis in Rodent Brains

2017 ◽  
Vol 12 (9) ◽  
pp. 1934578X1701200
Author(s):  
Rubens Batista Benedito ◽  
Mateus Feitosa Alves ◽  
Wendel Batista Pereira ◽  
Paula de Arruda Torres ◽  
Jéssica Pereira Costa ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Natural Compound ◽  
Perillyl Alcohol ◽  
Antinociceptive Activity ◽  
Histopathological Analysis ◽  
Histological Changes ◽  
Writhing Test ◽  
Antinociceptive Effects ◽  
Histopathological Evaluation ◽  
Tissue Changes

Perillyl alcohol (PA) is a natural compound found in essential oils. In this study, the antinociceptive activity of PA was evaluated using acetic acid and formalin tests. The involvement of the opioid system in its mechanism of action was investigated. Potential histological changes in the hippocampus and striatum were also assessed. In the acetic acid induced writhing tests, the mice pretreated with PA exhibited significant reductions in writhing. PA inhibited formalin injected paw licking response, and naloxone partially reversed the antinociceptive activity of perillyl alcohol during the writhing test. And as for the histopathological evaluation, PA did not cause significant tissue changes. This study suggests that PA possesses antinociceptive effects without significant hippocampus or striatum neurotoxicity, and that its activity involves opioid.

Antinociceptive Activity of Structural Analogues of Rotundifolone: Structure-Activity Relationship

2007 ◽  
Vol 62 (1-2) ◽  
pp. 39-42 ◽  
Author(s):  
Damião P. de Sousa ◽  
Edison V. M. Júnior ◽  
Fernando S. Oliveira ◽  
Reinaldo N. de Almeida ◽  
Xirley P. Nunes ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Structural Modification ◽  
Functional Group ◽  
Present Report ◽  
Antinociceptive Effect ◽  
Antinociceptive Activity ◽  
Writhing Test ◽  
Structure Activity ◽  
Structural Analogues ◽  
Limonene Oxide

Rotundifolone, a monoterpene isolated from the essential oil of the leaves of Mentha x villosa, is a constituent of several essential oils and known to have antinociceptive activity. Our recent study demonstrated that the analogues of rotundifolone showed also a significant antinociceptive effect. In the present report, to investigate the correlation between the structure and antinociceptive activity, rotundifolone and its analogues were evaluated in the acetic acid-induced writhing test in mice. All compounds showed to be more antinociceptive than rotundifolone against the pain response induced by acetic acid. Comparing the antinociceptive effect of rotundifolone with limonene oxide and (+)-pulegone, the results demonstrated that the epoxide group contributes as much as the ketone group to the antinociceptive activity of rotundifolone. Similarly, pulegone oxide and carvone epoxide were more antinociceptive than rotundifolone, thereby suggesting that the position of the functional group on the ring also influences the antinociceptive activity. (D)-Carvone produced maximal inhibition of the writhing response and was slightly more active than (+)-carvone. The study showed that by appropriate structural modification it may be possible to develop novel antinociceptive agents.

scholarly journals The Methanolic Extract fromMurraya koenigiiL. Inhibits Glutamate-Induced Pain and Involves ATP-Sensitive K+Channel as Antinociceptive Mechanism

2016 ◽  
Vol 2016 ◽  
pp. 1-6
Author(s):  
Nushrat Sharmin Ani ◽  
Sudip Chakraborty ◽  
Md. Moniruzzaman
Keyword(s):  
Acetic Acid ◽  
Potassium Channels ◽  
Methanolic Extract ◽  
Scientific Basis ◽  
K Channel ◽  
Dependent Manner ◽  
Glutamatergic System ◽  
Antinociceptive Effects ◽  
Wide Range ◽  
Antinociceptive Mechanisms

Murraya koenigiiL. is a perennial shrub, belonging to the family Rutaceae. Traditionally, the leaves of this plant are extensively used in treatment of a wide range of diseases and disorders including pain and inflammation. Although researchers have revealed the antinociceptive effects of this plant’s leaves during past few years, the mechanisms underlying these effects are still unknown. Therefore, the present study evaluated some antinociceptive mechanisms of the methanolic extract ofM. koenigii(MEMK) leaves along with its antinociceptive potential using several animal models. The antinociceptive effects of MEMK were evaluated using formalin-induced licking and acetic acid-induced writhing tests at the doses of 50, 100, and 200 mg/kg. In addition, we also justified the possible participations of glutamatergic system and ATP-sensitive potassium channels in the observed activities. Our results demonstrated that MEMK significantly (p<0.01) inhibited the pain thresholds induced by formalin and acetic acid in a dose-dependent manner. MEMK also significantly (p<0.01) suppressed glutamate-induced pain. Moreover, pretreatment with glibenclamide (an ATP-sensitive potassium channel blocker) at 10 mg/kg significantly (p<0.05) reversed the MEMK-mediated antinociception. These revealed that MEMK might have the potential to interact with glutamatergic system and the ATP-sensitive potassium channels to exhibit its antinociceptive activities. Therefore, our results strongly support the antinociceptive effects ofM. koenigiileaves and provide scientific basis of their analgesic uses in the traditional medicine.

scholarly journals INVESTIGATION OF ANTI-INFLAMMATORY AND ANTINOCICEPTIVE EFFECTS OF AQUEOUS EXTRACTS OF ARTEMISIA AFRA IN WISTAR RATS

2018 ◽  
Vol 11 (12) ◽  
pp. 190 ◽  
Author(s):  
Mavuto Gondwe ◽  
Anda Mpalala ◽  
Lusanda Zongo ◽  
David Kamadyaapa ◽  
Eugene Ndebia ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Biological Effects ◽  
Control Group ◽  
Paw Edema ◽  
Hot Plate ◽  
Traditional Practice ◽  
Hot Plate Test ◽  
Writhing Test ◽  
Antinociceptive Effects ◽  
Anti Inflammatory

Objective: The objective of the study was to evaluate the anti-inflammatory and antinociceptive effects of Artemisia afra.Methods: Animals were randomly divided into five groups of six animals each and administered with normal saline (2 ml/kg), indomethacin (10 mg/ kg), and A. afra at doses of 100, 200, and 400 mg/kg, respectively. For the anti-inflammatory activity, carrageenan-induced paw edema was used while the hot plate and acetic acid induced-writhing tests were used to assess the antinociceptive activity.Results: Pretreatment with A. afra at a dose of 100 mg/kg did not show any significant biological effects (p>0.05) for any of the three tests, when compared against saline-treated control group. At a dose of 200 mg/kg, A. afra demonstrated significant effects (p<0.01), during the 5th h reducing carrageenan-induced paw edema by 12%. The highest dose (400 mg/kg) of A. afra demonstrated more potent effects by decreasing the carrageenan-induced paw swelling (p<0.001–0.05) during the 3rd, 4th, and 5th h, by up to 38% when compared against saline-treated control group. Both the 200 and 400 mg/kg, A. afra doses achieved a significant increase (p<0.05) in reaction time in the hot plate test. In the acetic acid-induced writhing test, pretreatment with A. afra (400 mg/kg) significantly reduced pain by 39% (p<0.01) by comparison with the saline control.Conclusion: Experimental data demonstrated that aqueous extract of A. afra possesses anti-inflammatory and antinociceptive properties in experimental acute inflammation and pain. These findings support the usage of A. afra in managing inflammation and pain in traditional practice.

scholarly journals Antinociceptive Activity ofMelicope ptelefoliaEthanolic Extract in Experimental Animals

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Mohd Roslan Sulaiman ◽  
Azyyati Mohd Padzil ◽  
Khozirah Shaari ◽  
Syamimi Khalid ◽  
Wan Mastura Shaik Mossadeq ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Oral Administration ◽  
Ethanolic Extract ◽  
Antinociceptive Activity ◽  
Second Phase ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Experimental Animals ◽  
Antinociceptive Effects ◽  
Abnormal Behaviors

Melicope ptelefoliais a medicinal herb commonly used in Malaysia to treat fever, pain, wounds, and itches. The present study was conducted to evaluate the antinociceptive activity of theMelicope ptelefoliaethanolic extract (MPEE) using animal models of nociception. The antinociceptive activity of the extract was assessed using acetic acid-induced abdominal writhing, hot-plate, and formalin-induced paw licking tests. Oral administration of MPEE produced significant dose-dependent antinociceptive effects when tested in mice and rats using acetic acid-induced abdominal constriction test and on the second phase of the formalin-induced paw licking test, respectively. It was also demonstrated that MPEE had no effect on the response latency time to the heat stimulus in the thermal model of the hot-plate test. In addition, the antinociception produced by MPEE was not blocked by naloxone. Furthermore, oral administration of MPEE did not produce any effect in motor performance of the rota-rod test and in acute toxicity study no abnormal behaviors as well as mortality were observed up to a dose level of the extract of 5 g/kg. These results indicated that MPEE at all doses investigated which did not produce any sedative and toxic effects exerted pronounce antinociceptive activity that acts peripherally in experimental animals.

scholarly journals Amarisolide A and pedalitin as bioactive compounds in the antinociceptive effects of Salvia circinata

2019 ◽  
Vol 97 (3) ◽  
pp. 355 ◽  
Author(s):  
Gabriel Fernando Moreno-Pérez ◽  
María Eva González-Trujano ◽  
Martha Juana Martínez-Gordillo ◽  
Rubén San Miguel-Chávez ◽  
Francisco Alberto Basurto-Peña ◽  
...  
Keyword(s):  
Antinociceptive Effect ◽  
Folk Medicine ◽  
Gastrointestinal Diseases ◽  
Antinociceptive Activity ◽  
Bioactive Constituents ◽  
Response Curves ◽  
Reference Drug ◽  
Writhing Test ◽  
H Nmr ◽  
Antinociceptive Effects

<p align="left"><strong>Background</strong>: <em>Salvia circinata</em> is an endemic species of Mexico used in the folk medicine of Santiago Huauclilla, Oaxaca, mainly as remedy for gastrointestinal diseases.</p><p align="left"><strong>Hypothesis</strong>: If the extracts of <em>Salvia circinata</em> have secondary metabolites with antinociceptive activity, then the behavior of nociception in the model of “whriting” in mice will decrease.</p><p align="left"><strong>Specie studied</strong>:<strong> </strong><em>Salvia circinata </em>Cav. (Lamiaceae).</p><p align="left"><strong>Study site and years of study</strong>: <em>Salvia circinata </em>was collected in Santiago Huauclilla, Oaxaca, in July 2014.</p><p align="left"><strong>Methods</strong>: Firstly, the acute toxicity of <em>S. circinata</em> extracts was evaluated to calculate the LD<sub>50 </sub>with OECD method. Then, dose-response curves of the antinociceptive effect of <em>S. circinata</em> organic and aqueous extracts (1, 10, 30, 100, and 300 mg/kg) were obtained in the writhing test in mice. Furthermore, chromatographic techniques were applied to isolate the compounds and were identified by comparison of the values of <sup>1</sup>H NMR, <sup>13</sup>C NMR and ESIMS reported in the literature.</p><p align="left"><strong>Results</strong>: Our data showed significant antinociceptive activity in all the tested extracts. Amarisolide A and pedalitin were isolated in the ethyl acetate and methanol extracts, respectively and assayed at doses of 1, 5 and 10 mg/kg, i.p. All the compounds decreased nociception in mice in at least 50 % from a minimal dosage of 1 mg/kg, i.p. and in a similar manner than the reference drug ketorolac (1 mg/kg, i.p.).</p><p align="left"><strong>Conclusions</strong>: Our findings give evidence that <em>Salvia circinata </em>possesses antinociceptive activity depending on the presence of several known bioactive constituents, reinforcing its use in the Mexican traditional medicine to alleviate abdominal pain.</p>

Antinociceptive Activity of Lectins from Diocleinae Seeds on Acetic Acid-Induced Writhing Test in Mice

2009 ◽  
Vol 16 (9) ◽  
pp. 1088-1092 ◽  
Author(s):  
Fernanda Holanda ◽  
Andrelina Coelho-de-Sousa ◽  
Ana Assreuy ◽  
Jose Leal-Cardoso ◽  
Alana Pires ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Antinociceptive Activity ◽  
Writhing Test

Antidepressants enhance the antinociceptive effects of carbamazepine in the acetic acid-induced writhing test in mice

2006 ◽  
Vol 550 (1-3) ◽  
pp. 78-83 ◽  
Author(s):  
Mieko Aoki ◽  
Minoru Tsuji ◽  
Hiroshi Takeda ◽  
Yoichiro Harada ◽  
Jun Nohara ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Writhing Test ◽  
Antinociceptive Effects

scholarly journals Antinociceptive Activity of the Skin Secretion of Phyllomedusa rohdei (Amphibia, Anura)

Toxins ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 589
Author(s):  
Elena Lucia Anna Malpezzi-Marinho ◽  
Cristiane Isabel Silva Zanoni ◽  
Graziella Rigueira Molska ◽  
Camila Paraventi ◽  
Raphael Wuo-Silva ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Skin Extract ◽  
Skin Secretion ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Plate Test ◽  
Analgesic Effects ◽  
Opioid Receptor Antagonists ◽  
Pain Models ◽  
Antinociceptive Effects

Pain is a distressful experience that can have a major impact on an individual’s quality of life. The need for new and better analgesics has been further intensified in light of the current opioid epidemic. Substances obtained from amphibians have been shown to contain bioactive peptides that exert analgesic effects. The genus Phyllomedusa represents an important source of peptides and bioactive components. The aim of this study was to investigate the antinociceptive effects of the skin secretion of Phyllomedusa rohdei in rodent models of pain. The crude skin extract of P. rohdei was tested in different pain models: acetic acid-induced writhing test (mice), formalin test (rats), Von Frey electronic test for hypernociception induced by PGE2 (rats), and hot plate test (mice). Motor-impairing effects were tested using the rota-rod test. The results showed that the skin extract of P. rohdei exerted antinociceptive effects in all pain models tested. Particularly, the highest dose tested of the skin extract decreased acetic acid-induced writhing by 93%, completely blocked formalin-induced nociception both during the acute and inflammatory phases of the test, PGE2-induced hypernociception by 73% and increased latency to paw withdrawal in the hot plate test by 300%. The effects observed in the hot plate test were reversed by pretreatment with selective µ and κ, but not δ, opioid receptor antagonists, indicating a mechanism of action dependent on µ and κ opioid receptors. The results were not influenced by sedative effects. Further studies remain necessary to reveal the specific compounds involved in the antinociceptive effects of P. rohdei skin extract as a new therapeutic tool in pain management.

scholarly journals Methanol Extract of Dicranopteris linearis Leaves Attenuate Pain via the Modulation of Opioid/NO-Mediated Pathway

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 280 ◽  
Author(s):  
Zainul Amiruddin Zakaria ◽  
Rushduddin Al Jufri Roosli ◽  
Najihah Hanisah Marmaya ◽  
Maizatul Hasyima Omar ◽  
Rusliza Basir ◽  
...  
Keyword(s):  
Methanol Extract ◽  
Soluble Guanylyl Cyclase ◽  
Antinociceptive Activity ◽  
Opioid Antagonist ◽  
No Donor ◽  
Writhing Test ◽  
Thermal Nociception ◽  
Pain Models ◽  
Analgesic Agents ◽  
Dicranopteris Linearis

Dicranopteris linearis leaf has been reported to exert antinociceptive activity. The present study elucidates the possible mechanisms of antinociception modulated by the methanol extract of D. linearis leaves (MEDL) using various mouse models. The extract (25, 150, and 300 mg/kg) was administered orally to mice for 30 min priot to subjection to the acetic acid-induced writhing-, hot plate- or formalin-test to establish the antinociceptive profile of MEDL. The most effective dose was then used in the elucidation of possible mechanisms of action stage. The extract was also subjected to the phytochemical analyses. The results confirmed that MEDL exerted significant (p < 0.05) antinociceptive activity in those pain models as well as the capsaicin-, glutamate-, bradykinin- and phorbol 12-myristate 13-acetate (PMA)-induced paw licking model. Pretreatment with naloxone (a non-selective opioid antagonist) significantly (p < 0.05) reversed MEDL effect on thermal nociception. Only l-arginine (a nitric oxide (NO) donor) but not N(ω)-nitro-l-arginine methyl ester (l-NAME; a NO inhibitor) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a specific soluble guanylyl cyclase inhibitor) significantly (p < 0.05) modified MEDL effect on the writhing test. Several polyphenolics and volatile antinociceptive compounds were detected in MEDL. In conclusion, MEDL exerted the opioid/NO-mediated antinociceptive activity, thus, justify D. linearis as a potential source for new analgesic agents development.

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