Carbachol interactions with nonsteroidal anti-inflammatory drugs

2002 ◽  
Vol 80 (12) ◽  
pp. 1173-1179 ◽  
Author(s):  
H F Miranda ◽  
F Sierralta ◽  
G Pinardi
Keyword(s):  
Test Dose ◽  
Antinociceptive Activity ◽  
Simultaneous Administration ◽  
Response Curves ◽  
Additional Mechanism ◽  
Writhing Test ◽  
Prostaglandin Biosynthesis ◽  
Isobolographic Analysis ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

The inhibition of cyclooxygenase enzymes by nonsteroidal anti-inflammatory drugs (NSAIDs) does not completely explain the antinociceptive efficacy of these agents. It is known that cholinergic agonists are antinociceptive, and this study evaluates the interactions between carbachol and some NSAIDs. Antinociceptive activity was evaluated in mice by the acetic acid writhing test. Dose–response curves were constructed for NSAIDs and carbachol, administered either intraperitoneally (i.p.) or intrathecally (i.t.). The interactions of carbachol with NSAIDs were evaluated by isobolographic analysis after the simultaneous administration of fixed proportions of carbachol with each NSAID. All of the drugs were more potent after spinal than after systemic administration. The combinations of NSAIDs and carbachol administered i.p. were supra-additive; however, the i.t. combinations were only additive. Isobolographic analysis of the coadministration of NSAIDs and carbachol and the fact that atropine antagonized the synergistic effect suggest that carbachol may strongly modulate the antinociceptive activity of NSAIDs; thus, central cholinergic modulation would be an additional mechanism for the antinociceptive action of NSAIDs, unrelated to prostaglandin biosynthesis inhibition.Key words: antinociception, nonsteroidal anti-inflammatory drugs, cholinergic, carbachol, writhing test.

Synthesis of new ibuprofen hybrid conjugates as potential anti-inflammatory and analgesic agents

2020 ◽  
Vol 12 (15) ◽  
pp. 1369-1386
Author(s):  
Siva S Panda ◽  
Adel S Girgis ◽  
Hitesh H Honkanadavar ◽  
Riham F George ◽  
Aladdin M Srour
Keyword(s):  
Writhing Test ◽  
Rat Paw Edema ◽  
Analgesic Agents ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Rat Paw ◽  
Inhibition Studies

Background: A new set of hybrid conjugates derived from 2-(4-isobutylphenyl)propanoic acid (ibuprofen) is synthesized to overcome the drawbacks of the current non-steroidal anti-inflammatory drugs. Results & methodology: Synthesized conjugates were screened for their anti-inflammatory, analgesic and ulcerogenic properties. Few conjugates were found to have significant anti-inflammatory properties in the carrageenan-induced rat paw edema test, while a fair number of conjugates showed promising peripheral analgesic activity in the acetic acid-induced writhing test as well as central analgesic properties in the in vivo hot plate technique. The newly synthesized conjugates did not display any ulcerogenic liability. Conclusion: In vitro, COX-1 and COX-2 enzyme inhibition studies raveled compound 7e is more selective toward COX-2 compared with ibuprofen.

Anti-Inflammatory and Antinociceptive Activity of Flavonoids Isolated from Viscum album ssp. album

2006 ◽  
Vol 61 (1-2) ◽  
pp. 26-30 ◽  
Author(s):  
Didem Deliorman Orhan ◽  
Esra Küpeli ◽  
Erdem Yesilada ◽  
Fatma Ergun
Keyword(s):  
Ethyl Acetate ◽  
Inflammatory Diseases ◽  
Ethyl Acetate Fraction ◽  
Viscum Album ◽  
Antinociceptive Activity ◽  
Paw Edema ◽  
Writhing Test ◽  
Activity Assessment ◽  
Edema Model ◽  
Anti Inflammatory

Abstract Viscum album L. has been used in the indigenous systems of medicine for treatment of headache and some inflammatory diseases. In order to evaluate this information, antinociceptive and anti-inflammatory activities of the five flavonoids (5,7-dimethoxy naringenin or 4′,6′- dimethoxy chalcononaringenin) derivatives, isolated from the ethyl acetate fraction of the extract from V. album ssp. album, were investigated, namely 5,7-dimethoxy-flavanone-4′-O- β-ᴅ-glucopyranoside (1), 2′-hydroxy-4′,6′-dimethoxy-chalcone-4-O-β-ᴅ-glucopyranoside (2), 5,7-dimethoxy-flavanone-4′-O-[2″-O-(5‴-O-trans-cinnamoyl)-β-ᴅ-apiofuranosyl]-β-ᴅ-glucopyranoside (3), 2′-hydroxy-4′,6′-dimethoxy-chalcone-4-O-[2″-O-(5‴-O-trans-cinnamoyl)-β-ᴅ-apiofuranosyl]- β-ᴅ-glucopyranoside (4), 5,7-dimethoxy-flavanone-4′-O-[β-d-apiofuranosyl- (152)]-β-ᴅ-glucopyranoside (5). For the antinociceptive activity assessment the p-benzoquinone- induced writhing test and for the anti-inflammatory activity the carrageenan-induced hind paw edema model in mice were used. The ethyl acetate fraction in a dose of 250 mg/kg as well as compounds 2 and 5 in a 30 mg/kg dose were shown to possess remarkable antinociceptive and anti-inflammatory activities per os without inducing any apparent acute toxicity as well as gastric damage

An isobolographic analysis of the anti-nociceptive effect of geraniin in combination with morphine or diclofenac

2018 ◽  
Vol 29 (2) ◽  
pp. 201-209 ◽  
Author(s):  
Eric Boakye-Gyasi ◽  
Ella Anle Kasanga ◽  
Elvis Ofori Ameyaw ◽  
Wonder Kofi Mensah Abotsi ◽  
Robert Peter Biney ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Aqueous Extract ◽  
Dose Response ◽  
Formalin Test ◽  
Fixed Ratio ◽  
Test Dose ◽  
Response Curves ◽  
Isobolographic Analysis ◽  
Aerial Parts

AbstractBackground:Geraniin, a dehydroellagitannin, is a major component of the aqueous extract of the aerial parts ofPhyllanthus muellerianus(Kuntze) Exell. (Euphorbiaceae). SeveralPhyllanthusspecies are traditionally used for painful disorders. The anti-nociceptive effects of the aqueous extract of the aerial parts ofP. muellerianusand of geraniin have been scientifically established. The aim of the paper is to determine whether a combination of geraniin and diclofenac or geraniin and morphine leads to better anti-nociceptive effects.Methods:The nature of the interactions of morphine and diclofenac with geraniin was evaluated by undertaking the isobolographic analysis. Mice were treated with geraniin (3–30 mg/kg), morphine (1–10 mg/kg), and diclofenac (10–100 mg/kg) to obtain the ED50values of the agents in the formalin test. Dose-response curves were then obtained and analyzed after the co-administration of geraniin with morphine or diclofenac in fixed ratio (1:1) combinations based on specific fractions (1/2, 1/4, and 1/8) of their respective ED50values for the formalin test.Results:Geraniin was less potent than morphine but more potent than diclofenac in the formalin-induced nociception. The isobolographic analysis of geraniin/morphine (G/M) and geraniin/diclofenac combinations (G/D) at different fractions revealed the potentiation of their anti-nociceptive effects. The degrees of potentiation, which were calculated as interaction indices, showed synergism for both combinations in both phase I (G/M: 0.040, G/D: 0.017) and phase II (G/M: 0.004, G/D: 0.002) of the formalin test.Conclusions:The present study demonstrates synergism for the co-administration of geraniin with both morphine and diclofenac.

Determination of the Therapeutic Mean Effective Doses of Several Anti-inflammatory Agents in Adjuvant Arthritic Rats

1974 ◽  
Vol 52 (4) ◽  
pp. 791-796 ◽  
Author(s):  
R. R. Martel ◽  
J. Klicius ◽  
F. Herr
Keyword(s):  
Dose Response ◽  
Probit Analysis ◽  
Relative Potency ◽  
Response Curves ◽  
Treatment Groups ◽  
Clinical Observations ◽  
Inflammatory Drugs ◽  
Dose Response Curves ◽  
Anti Inflammatory ◽  
Therapeutic Test

The large variation in the severity of the arthritic response of the adjuvant-injected rat often makes it impossible to obtain statistically manageable dose–response curves with anti-inflammatory drugs. Consequently, the relative potency of anti-inflammatory drugs generally was not established. In the present study, with a modification of the therapeutic test, reliable dose–response curves were obtained with seven anti-inflammatory drugs. With this method the "therapeutic" mean effective dose (ED50) and relative potency were calculated by probit analysis. Charles River rats were injected in the left hind paw with adjuvant. On day 14, rats with an injected paw volume of 4–6 ml that increased by at least 0.5 ml between days 10 and 14 were selected for drug treatment. Groups of 6–12 rats with a mean injected paw volume of 5–5.5 ml were formed. Dosing with compounds was started on day 14 and continued daily until day 22 (nine injections). Ninety-four percent of the arthritic control rats showed a further increase in injected paw size between days 14 and 22 (mean, 1.06 ± 0.12 ml) whereas rats dosed with anti-inflammatory compounds showed a dose-related decrease in paw size during the same period. A decrease of 0.5 ml or more between days 14 and 22 was considered to be a therapeutic effect, smaller decreases were taken as no effect. The oral ED50's in milligrams per kilogram were indomethacin, 0.22 ± 0.05; prednisolone, 3.49 ± 1.0; hydrocortisone, 12.4 ± 3.0; phenylbutazone, 13.27 ± 2.7; mefenamic acid 20.10 ± 5.8; aminopyrine, 129.95 ± 25.3; and aspirin, 279.0 ± 24.6. Except for aspirin, the relative potency of the compounds studied by this therapeutic test (chronic) was comparable to that reported for the acute carrageenin assay. Aspirin appears to be markedly less active in chronic inflammation than in acute. This finding is consistent with both experimental and clinical observations.

scholarly journals Analgesic and anti-inflammatory activity of 5,7-diacyl-3-H(alkіl)-6- aryl-5H-[1,2,4]triazol[3,4-b][1,3,4]tіadiazin derivaties

2015 ◽  
Vol 17 (2) ◽  
Author(s):  
O. Ye. Yadlovskyi ◽  
А. Ya. Koval ◽  
N. M. Seredynska ◽  
T. A. Bukhtiarova ◽  
T. A. Bershova ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Specific Activity ◽  
Reference Product ◽  
Antinociceptive Effect ◽  
Antinociceptive Activity ◽  
Hot Plate ◽  
Carrageenan Edema ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Derivatives Of

The search for new analgesic and anti-inflammatory drugs, exceeding by efficacy and/or safety the existing<br />analogues is very important and relevant. The nitrogenous heterocycles are promising in this respect, in particular,<br />the compounds containing an imidazole triazol and tіadiazin moiety. The aim of the current study was to investigate<br />the antiexudative and antinociceptive activity of new derivatives of 5,7-diacyl-3-H(alkyl)-6-aryl-5H[1,2,4]triazol[3,4-b]<br />[1,3,4]thiadiazine.<br />The antinociceptive and antiexudative activity studies were carried out on the white nonlinear mice. The<br />experimental evaluation of specific activity was carried out on the models “Hot plate”, acetic acid induced writhing<br />(antinociceptive action) and carrageenan edema (antiexudative action). The substance was used in a single oral rout<br />administration in a dose of 25 mg/kg. Ketorolac was used as a reference product in the dose of 25 mg/kg (models<br />“Hot plate”, acetic acid induced writhing). Diclofenac was used as a reference product in the dose of 25 mg/kg on<br />the model carrageenan edema. The experimental study showed the antinociceptive and antiexudative effects of the<br />derivatives. The antinociceptive activity of 5,7-diacyl-3-H(alkіl)-6-aryl-5H[1,2,4]triazol[3,4-b][1,3,4]tіadiazin derivaties<br />related to the modification structure in the para position of benzene ring. The antiexudative activity is associated with<br />acetyl groups thiadiazine ring. The most promising compound IFT_247 showed a significant antinociceptive effect,<br />which is comparable to an active comparator ketorolac: “Hot plate” +232.46 % and +112.71 %; acetic acid induced<br />writhing -66.67 % and -61.02 %, respectively.

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>

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