scholarly journals Design and evaluation of pharmacological properties of a new 1,3,4-thiadiazolylamide derivative of 2-propylpentanoic acid

2021 ◽  
Vol 7 (4) ◽  
pp. 89-98
Author(s):  
Alexandr S. Malygin ◽  
Victor V. Yasnetsov
Keyword(s):  
Analgesic Effect ◽  
Intraperitoneal Administration ◽  
Maximal Electroshock ◽  
Thermal Stimulus ◽  
Hot Plate ◽  
Rotarod Test ◽  
Hot Plate Test ◽  
Plate Test ◽  
Antiepileptic Activity ◽  
Bar Test

Introduction: The use of the pharmacophoric approach is a promising direction for modifying the chemical structure of 2-propylpentanoic (valproic) acid in order to obtain new drugs. Materials and methods: In the experiments on mice, acute toxicity, neurotoxicity, antiepileptic activity and analgesic effect of N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propylpentanamide (valprazolamide) were evaluated. LD50 was determined by probit analysis. Neurotoxicity was determined in a rotarod test and a bar test in mice. The effects of valprazolamide on the exploratory behavior of mice in open field test and in a light/dark transition test were evaluated. Its antiepileptic activity was tested in mice against seizures induced by maximal electroshock, pentylenetetrazole (scPTZ); isoniazid, thiosemicarbazide, pilocarpine, and camphor. The analgesic effect was studied in a hot plate test. Results and discussion: N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propylpentanamide was obtained by introducing pharmacophores into the structure of 2-propylpentanoic acid: a substituted amide group and an electron-donor domain of 1,3,4-thiadiazole. The LD50 value for intraperitoneal administration of a new 2-propylpentanoic acid: derivative to mice was 924.8 mg/kg, and the TD50 value in the rotarod test and the bar test were 456.7 mg/kg and 546.7 mg/kg, respectively. The suppression of orienting responses in the animals was noted when it was administered in neurotoxic doses. Valprazolamide showed the most antiepileptic activity on models of MES, scPTZ and isoniazid antagonism tests. The ED50 values were 138.4 mg/kg, 74.5 mg/kg, and 126.8 mg/kg, respectively. The therapeutic indices for these models of epilepsy were 6.7; 12.4; 7.3, and protective index – 3.3; 6.1 and 3.6, respectively. In the hot plate test, valprazolamide increased the latency period before a defensive response to a thermal stimulus (ED50 165 mg/kg). Conclusion: N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propylpentanamide is a new 1,3,4-thiadiazolylamide derivative of 2-propylpentanoic acid with antiepileptic and analgesic activities, which belongs to the group of low-toxic agents. Graphic abstract N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propylpentanamide (3D) LD50=924.8 mg/kg (mice, intraperitoneally) TD50=456.7 mg/kg (rotarod, mice, intraperitoneally) ED50=138.4 mg/kg (MES, mice, intraperitoneally) ED50=74.5 mg/kg (scPTZ, mice, intraperitoneally)

scholarly journals Analgesic Activity of the Kappa Opioid Receptor Agonist RU-1205 in Rats

2018 ◽  
Vol 3 (2) ◽  
pp. 13 ◽  
Author(s):  
AA Spasov ◽  
OY Grechko ◽  
DM Shtareva ◽  
AI Raschenko ◽  
Natalia Eliseeva ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Analgesic Activity ◽  
Analgesic Effect ◽  
Physical Dependence ◽  
Receptor Activation ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Plate Test

Introduction: Opioid analgesics are the most efficient and widely used drugs for the management of moderate to severe pain. However, side effects associated with mu receptor activation, such as respiratory depression, tolerance and physical dependence severely limit their clinical application. Currently, the kappa-opioid system is the most attractive in terms of the clinical problem of pain, because kappa-agonists do not cause euphoria and physical dependence. The purpose of this study was to evaluate the antinociceptive effect of the novel compound - RU-1205. Methods: The analgesic activity of RU-1205 was studied on nociceptive models that characterize the central and peripheral pathways of pain sensitivity (hot plate test, electrically induced vocalisation, formalin test, writhing test). Results: RU-1205 exhibited highly potent antinociceptive effects in rodent models of acute pain with ED50 values of 0.002 - 0.49 mg /kg. Pretreatment with the κ-opioid receptor antagonist norBinaltorphimine significantly attenuated the analgesic activity of investigated substance in a hot plate test. Conclusions: It was established that the compound shows a significant dose-dependent central and peripheral analgesic effect. It was assumed kappa-opioidergic mechanism of analgesic effect of RU-1205.

scholarly journals Preparation and Analysis of New 1,3,5-Trisubstituted-2-Pyrazolines Derivative for Their Analgesic Potential

2021 ◽  
pp. 153-164
Author(s):  
Jitendra Kumar Chaudhary ◽  
Alok Pal Jain ◽  
O. P. Tiwari
Keyword(s):  
Acetic Acid ◽  
Analgesic Effect ◽  
Latency Time ◽  
Hot Plate ◽  
Phenyl Hydrazine ◽  
Hot Plate Test ◽  
Test Technique ◽  
Plate Test ◽  
Withdrawal Latency ◽  
In Series

The goal of the study was to develop, synthesise, and characterise a novel 1,3,5-trisubstituted-2-pyrazolines derivative, as well as to assess its analgesic potential. The reaction of chalcone derivatives with 4-hydrazinylbenzene sulfonamide hydrochloride and phenyl hydrazine hydrochloride yielded 1,3,5-tri-substituted-2-pyrazolines derivatives. The IR, 1HNMR, and mass spectrum analyses were used to characterise a total of sixteen substances. Analgesic activity of the proposed substances has been tested. The analgesic effect of the produced compounds was tested using two methods: the hot plate test technique and acetic acid induced writhing in mice. To compare the effectiveness, pentazocine and acetyl acetic acid were utilised as reference drugs. The hot plate test technique and acetic acid induced writhing in mice were used to assess the analgesic effect of the 16 produced chemical series A1-A8, and B1-B8. The evaluation's outcomes were viewed using Pentazocine and acetyl acetic acid as the standard drugs. In a 90-minute hot plate test, compounds A2 (10.30 s), A4 (9.45 s), A7 (11.65 s), and A8 (11.26 s) showed a delay in paw withdrawal latency time. Compounds B2 (9.10 s) and B7 (10.42 s) prolong the paw withdrawal latency time after 90 minutes in series B1-B8, reduce the pain feeling, and inhibit pain induced by heat methods. Compounds A2, A5, A6, A7, and A8 from Series A1-A8 showed 83.00, 76.01, 80.34, 86.99, 88.15 percent inhibition, substantially (p0.05 and p0.001, respectively), and decreased the number of wriths caused by 0.6 percent acetic acid at a dosage of 10 mg/kg. Acetylsalicylic acid (10 mg/kg) appears to be more successful in lowering the number of wriths, with a 99.0% reduction in the number of wriths (p0.001). B1, B3, and B4 have the least amount of active activity. These all finding suggest that these synthesized compounds have the potential as analgesic agent.

Antinociceptive Effect of Clomipramine Through Interaction with Serotonin 5-Нт2 And 5-Нт3 Receptor Subtypes

Folia Medica ◽  
2012 ◽  
Vol 54 (4) ◽  
pp. 69-77 ◽  
Author(s):  
Ilia D. Kostadinov ◽  
Delian P. Delev ◽  
Ivanka I. Kostadinova
Keyword(s):  
Acetic Acid ◽  
Analgesic Effect ◽  
Antinociceptive Effect ◽  
Positive Control ◽  
Control Group ◽  
Receptor Subtypes ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Plate Test ◽  
Acid Test

Abstract INTRODUCTION: Tricyclic antidepressants are used in the treatment of various pain syndromes. The antidepressant clomipramine inhibits predominantly the reuptake of serotonin in the central nervous system. The mechanism of its analgesic effect is not fully understood. The AIM of the present study was to find experimentally any dose-effect dependence in the analgesic effect of clomipramine and the involvement of the 5-НТ2 and 5-НТ3 receptors in the mechanism of this effect. Material and methods: Fifty male Wistar rats were used in the study allocated to five groups (10 animals each): a saline treated control group, one positive control group treated with metamizole and three experimental groups treated with intraperitoneally administered clomipramine in doses of 5, 10 and 20 mg/kg bw, respectively. To study the role of 5-НТ2 and 5-НТ3 receptors in this effect we used another five groups (10 animals each): control, positive control and three experimental groups treated with clomipramine only, clomipramine and granisetrone and clomipramine and cyproheptadine, respectively. Three nociceptive tests were used: the hot plate test, analgesimeter and the acetic acid-induced writhing test. To gauge the antinociceptive action we used the increased latency in the hot plate test expressed as maximum possible effect % (%MPE), the increase in paw pressure to withdraw the hind paw in analgesimeter and decrease in the number of spinal cord writhes in the acetic acid test. RESULTS: Clomipramine in a dose of 20 mg/kg bw significantly increased the %MPE in hot plate test and the pressure to withdraw the hind paw in the analgesimeter when compared with the control. In the acetic acid test clomipramine decreased non-significantly the number of writhes compared with the controls. Granisetrone reduced non-significantly the antinociceptive effect of clomipramine in all tests. Cyproheptadine potentiated the analgesic effect of clomipramine in acetic acid test and decreased it significantly in the hot plate test. In analgesimeter cyproheptadine decreased significantly the paw pressure to withdraw the tested hind paw at 1 hour and non-significantly at 2 hours. CONCLUSION: Clomipramine in the dose of 20 mg/kg bw has a pronounced antinociceptive affect towards thermal and mechanical pain stimulation. The 5-HT2 and 5-HT3 receptor subtypes are very likely involved in the mechanism of this effect.

scholarly journals Borneol, a Bicyclic Monoterpene Alcohol, Reduces Nociceptive Behavior and Inflammatory Response in Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Jackson Roberto Guedes da Silva Almeida ◽  
Grasielly Rocha Souza ◽  
Juliane Cabral Silva ◽  
Sarah Raquel Gomes de Lima Saraiva ◽  
Raimundo Gonçalves de Oliveira Júnior ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Motor Coordination ◽  
Nociceptive Behavior ◽  
Hot Plate ◽  
Rotarod Test ◽  
Hot Plate Test ◽  
Plate Test ◽  
Strength Tests ◽  
Anti Inflammatory ◽  
Motor Abnormality

Borneol, a bicyclic monoterpene, has been evaluated for antinociceptive and anti-inflammatory activities. Antinociceptive and anti-inflammatory activities were studied by measuring nociception by acetic acid, formalin, hot plate, and grip strength tests, while inflammation was prompted by carrageenan-induced peritonitis. The rotarod test was used to evaluate motor coordination. Borneol produced a significant (P<0.01) reduction of the nociceptive behavior at the early and late phases of paw licking and reduced the writhing reflex in mice (formalin and writhing tests, resp.). When the hot plate test was conducted, borneol (in higher dose) produced an inhibition (P<0.05) of the nociceptive behavior. Such results were unlikely to be provoked by motor abnormality. Additionally, borneol-treated mice reduced the carrageenan-induced leukocytes migration to the peritoneal cavity. Together, our results suggest that borneol possess significant central and peripheral antinociceptive activity; it has also anti-inflammatory activity. In addition, borneol did not impair motor coordination.

scholarly journals Analgesic Effect of Dayak Onion (Eleutherine americana (Aubl.) Merr.) on Mice (Mus musculus) by Hot Plate Test Method

2021 ◽  
Vol 4 (1) ◽  
pp. 22
Author(s):  
Muhammad Hafizh ◽  
Danti Nur Indiastuti ◽  
Indri Safitri Mukono
Keyword(s):  
Response Time ◽  
Analgesic Effect ◽  
Latency Period ◽  
Test Method ◽  
Control Group ◽  
Test Results ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Plate Test ◽  
Eleutherine Americana

Introduction: Pain is an unpleasant experience that reduces a person's quality of life. Pain related complain can be treated by administering analgesic drugs. Several studies show that the availability of analgesics is still low, especially opioid analgesics. Dayak onion (Eleutherine americana (Aubl.) Merr.) are used by the Dayaks to relieve pain. Several empirical studies have shown that Dayak onion contain compounds including quercetin as a potential analgesic. This research aimed to investigate the potential analgesic effect of Dayak onion using hot plate method.Methods: The research was conducted experimentally on 36 BALB/c male mice which randomly divided into 6 different treatment groups of Dayak onion exctract, aspirin, codein and aquadest. Each group were thermally pain-induced for latency period measurement by the hot plate test method. Obtained data were processed using Analysis of Variance (ANOVA) followed by Dunnett test.Results: There was a difference in the latency period between the baseline response time and the response time after being treated in each group. ANOVA test results showed significant results (p<0.05) so that the resulting latency period was significant. Dunnett test results showed significant results (p<0.05) in negative control group. Based on these results, Dayak onion are proven to have an analgesic effect on heat stimulation.Conclusion: Dayak onion possess significant analgesic effect on thermally pain-induced mice. Dayak onion extract 90 mg/kg mouse produced better analgesic effects than aspirin 65 mg/kg mouse.

scholarly journals Analgesic effect of intrathecally administered orexin-A in the rat formalin test and in the rat hot plate test

2002 ◽  
Vol 137 (2) ◽  
pp. 170-176 ◽  
Author(s):  
Tatsuo Yamamoto ◽  
Natsuko Nozaki-Taguchi ◽  
Tanemichi Chiba
Keyword(s):  
Analgesic Effect ◽  
Formalin Test ◽  
Hot Plate ◽  
Orexin A ◽  
Hot Plate Test ◽  
Plate Test

Evaluation of the Anti-Inflammatory and Antinociceptive Properties of p-Cymene in Mice

2012 ◽  
Vol 67 (1-2) ◽  
pp. 15-21 ◽  
Author(s):  
Leonardo R. Bonjardim ◽  
Edisleide S. Cunha ◽  
Adriana G. Guimarães ◽  
Michele F. Santana ◽  
Makson G. B. Oliveira ◽  
...  
Keyword(s):  
Nervous System ◽  
Leukocyte Migration ◽  
Autonomous Nervous System ◽  
Second Phase ◽  
Thermal Stimulus ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Plate Test ◽  
The Central Nervous System ◽  
Anti Inflammatory

We attempted to identify the antinociceptive and anti-inflammatory actions of the monoterpene p-cymene. Firstly, behavioural screening was carried out to verify the influence of p-cymene [25, 50, and 100 mg/kg intraperitoneal (i.p.)] on the central nervous system (CNS) activity. The antinociceptive activity of p-cymene was evaluated by the acetic acidinduced writhing response, formalin, and hot-plate test, respectively. The leukocyte migration induced by injection of carrageenan was used to assess the anti-inflammatory activity. p-Cymene showed depressant activity on CNS after 4 h of treatment and also a possible action on the autonomous nervous system (ANS), mainly at the dose of 100 mg/kg (i.p.). It was found that p-cymene (50 and 100 mg/kg, i.p.) significantly (p < 0.05) reduced the writhing responses induced by acetic acid. p-Cymene also decreased the licking time in the first and second phase, respectively, of the formalin test. The results of the hot-plate test showed that all doses of p-cymene increased significantly the latency time of the response to the thermal stimulus in both licking and jumping parameters. In addition, there was a significantly (p < 0.05) decreased leukocyte migration at all doses of p-cymene. The experimental data demonstrate that p-cymene possesses antinociceptive and anti-inflammatory activities

scholarly journals Antinociceptive and Anti-Inflammatory Activities ofTeucrium persicumBoiss. Extract in Mice

Scientifica ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Abdolhossein Miri ◽  
Javad Sharifi-Rad ◽  
Kaveh Tabrizian ◽  
Ali Akbar Nasiri
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Analgesic Effect ◽  
Formalin Test ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Plate Test ◽  
Cotton Pellet ◽  
Anti Inflammatory

Background.Therapeutic properties ofTeucriumspecies as antioxidant, antibacterial, analgesic, anticancer, diuretic, and tonic compounds have been proved earlier.Materials and Methods. In this study, the antinociceptive and anti-inflammatory effects of the aqueous extract ofTeucrium persicumon chronic pain, sciatic nerve ligation as a model of neuropathic pain, and inflammatory models were investigated by formalin, hot-plate, and cotton pellet-induced granuloma models in mice, respectively.T. persicumaqueous extracts (100, 200, and 400 mg/kg) were orally gavaged for one week. On 8th day, the time spent and the number of lickings were recorded in formalin test. Morphine and Diclofenac were used intraperitoneally as positive controls. In sciatic nerve ligated animals, as a model of neuropathic pain, doses (100, 200, and 400 mg/kg) ofT. persicumextract (TPE) were orally gavaged for 14 consecutive days. The analgesic effect of this extract was examined 14 days after sciatic nerve ligation using the hot-plate test. Controls received saline and Imipramine (40 mg/kg, i.p.) was used a positive control for neuropathic pain model.Results.In the formalin test, a week oral gavage of all TPE doses (100, 200, and 400 mg/kg) caused a significant decrease on the licking response compared to the control negative animals. In the hot-plate test, doses of 200 and 400 mg/kg showed significant analgesic effects in sciatic nerve ligated animals. Oral gavaged of TPE revealed significant analgesic effect on chronic pain in both formalin test and sciatic nerve ligated animals. The TPEs did not have any significant anti-inflammatory effects in cotton pellet-induced granuloma formation in mice.Conclusions.These results suggest that the aqueous extract fromT. persicumBoiss. produced antinociceptive effects. Its exact mechanism of action still remains indistinct.

scholarly journals Analgesic properties of dealcoholized extract of Acorus Calamus Leaves

2021 ◽  
pp. 21-25
Author(s):  
Lyudmyla Derymedvid ◽  
Lyudmyla Korang
Keyword(s):  
Analgesic Effect ◽  
Latency Period ◽  
Pain Syndrome ◽  
Immersion Test ◽  
Acorus Calamus ◽  
Plate Model ◽  
Narcotic Analgesics ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Plate Test

Opioid and non-narcotic analgesics, non-steroidal anti-inflammatory agents, anesthetics, antidepressants, myorelaxants, combined agents and phytopreparations are widely used for the treatment of pain syndrome. One of the promising phytogenic objects with potential analgesic properties is the Acorus calamus (Sweet Flag). The aim: the purpose of the study is to determine the analgesic effect of the dealcoholized extract of Acorus calamus leaves (DEAL) on a model of pain in the "Hot plate" test and in the test of tail heat immersion. Materials and methods. During the experimental study, the pharmacological methods have been used. The analgesic properties of DEAL were studied in mice on the "Hot plate" model using the Hot / Cold Plate (Bioseb, France) and in the test of the heat immersion in rats. The results. On the models of pain in the "Hot plate" and tail heat immersion tests, the analgesic effect of the dealcoholized extract of Acorus calamus leaves (DEAL) is determined. On the "Hot plate" model, the use of DEAL probably increased the duration of the latency period. According to the analgesic effect of DEAL and metamizol sodium were comparable to each other continues to 1 and 1.5 hours of experiment, but starting with 2 hours of experiment the analgesic action of metamizol sodium statistically exceeded the analgesic effect of DEAL. In the test of heat immersion tail in rats, DEAL increased the latency period of shocking of the rats’ tail compared to the starting background by 43.13 % as well as metamizol sodium by 66.6 %. The studies have shown the presence of moderate analgesic effects of DEAL in the investigated dose. Conclusions. The analgesic effect of a dealcoholized extract of Acorus calamus leaves (DEAL) on a model of pain in the "Hot plate" and heat tail immersion tests has been carried out. Under the "Hot plate" test in mice, DEAL produces a distinct analgesic effect, however, slightly inferior to the severity of metamizol sodium. Presence of moderate analgesic properties of DEAL has been verified in comparison with the metamizel sodium in thetail heat immersion test in rats. The obtained results indicate the influence of DEAL on the central mechanisms of pain formation

scholarly journals Anti-inflammatory and Analgesic Effects in Rodent Models of Ethanol Extract of Clausena anisata Roots and their Chemical Constituents

2017 ◽  
Vol 12 (1) ◽  
pp. 1934578X1701200 ◽  
Author(s):  
Emmanuel Kofi Kumatia ◽  
Kofi Annan ◽  
Rita Akosua Dickson ◽  
Abraham Yeboah Mensah ◽  
Isaac Kingsley Amponsah ◽  
...  
Keyword(s):  
Analgesic Activity ◽  
Crude Extract ◽  
Analgesic Effect ◽  
Chemical Constituents ◽  
Ethanol Extract ◽  
Phytochemical Analysis ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Plate Test ◽  
Anti Inflammatory

The in vivo anti-inflammatory and analgesic activities of the crude ethanol extract and chemical constituents of Clausena anisata roots were investigated. The crude extract, which was devoid of any visible acute toxicity, displayed significant anti-inflammatory effect at the dose of 1000 mg/kg (p.o.) when assessed using the carrageenan-induced oedema model. In the acetic acid-induced writhing and hot plate tests, it produced a very significant ( p < 0.001), dose-dependent analgesic effect, with maximum analgesic activity of 72.1% at 1000 mg/kg (p.o.). Phytochemical analysis of the crude extract resulted in the isolation of four coumarins (anisocoumarin B, osthol, imperatorin and xanthotoxol) and a carbazole alkaloid, heptaphylline. Among the isolated compounds, osthol and anisocoumarin B produced the highest anti-inflammatory activity at 9 mg/kg (p.o.): slightly better than the positive control, indomethacin. Except for xanthotoxol, all the isolated compounds administered at 6 mg/kg (p.o.) produced significant analgesic activity and higher than diclofenac; with heptaphylline being the most potent (48.7%). The analgesic activity of anisocoumarin B (50.4%) was the highest among the isolates tested and the standard, tramadol, in the hot plate test. The nonselective opioid receptor antagonist, naloxone, abolished the analgesic effect of the crude extract and the tested isolates (anisocoumarin B and xanthotoxol) in the hot plate test suggesting an effect via the central opioidergic system. These findings provide the scientific basis for the use of C. anisata roots in traditional medicine as anti-inflammatory and analgesic agents.

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