Analgesic Activity In Mice Research Articles

Pharmacological Potential of Tetrahydrofurano/Pyrano Quinoline and Benzo[b]furoindolyl Derivatives in Acute Inflammation, Pain and Oxidative Stress.

Investigation of the pharmacological potential of Tetrahydrofurano/pyrano quinoline and Benzo [b]furoindolyl derivatives in acute inflammation, pain and oxidative stress. Tetrahydrofurano/ pyrano quinoline and Benzo[b]furoindolyl were evaluated for anti-inflammatory activity by carrageenan-induced hind paw edema in rats. Analgesic activity in mice was assessed by both peripheral and central analgesic models. The free radical scavenging activity of the synthetic compound was analyzed by the in vivo antioxidant assays, by measuring the antioxidant enzymes such as Superoxide dismutase (SOD), Catalase and Peroxidase from the liver homogenate and the in vitro antioxidant activity was evaluated by DPPH photometric assay, Hydroxyl radical scavenging and Lipid Peroxidation assay. The compounds had substantially inhibited the inflammation induced by subcutaneous carrageenan injection. The same compounds had demonstrated remarkable central and peripheral analgesic activity with potent free radical scavenging activity as evident from both in vitro and in vivo antioxidant assays. Tetrahydrofurano/pyrano quinoline and Benzo[b]furoindolyl derivatives exhibit varied pharmacological activities that include anti-inflammatory, analgesic and antioxidant activity.

In Vitro Membrane Stabilizing And In Vivo Analgesic Activities Of Dipterocarpus Turbinates Gaertn

The methanol extract of leaves of Dipterocarpus turbinatus Gaertn. and its Kupchan fractions were screened for in vitro membrane stabilization while the methanolic crude extract was evaluated for in vivo analgesic activity in mice at 200- and 400- mg/kg b.w. In heat- and hypotonic solution- induced conditions, the crude methanol extract inhibited haemolysis of human erythrocyte by 62.40±1.43% and 69.14±2.05%, respectively as compared to 70.37±0.95% and 40.60±1.65% demonstrated by the standard acetyl salicylic acid. Moreover, the analgesic activity was determined for its central and peripheral pharmacological actions using tail immersion and formalin-induced writhing test at 200- and 400- mg/kg b.w. The extract significantly (P<0.05) influenced the formalin-induced writhing in a dose dependent manner with the highest activity observed at 400 mg/kg b.w. (34.33%) when compared with the standard drug, acetyl salicylic acid (42.64%). A significant dose-dependent increase (P<0.05) of latency period was also observed in tail immersion method.

Seasonal Effects on HPLC-DAD-UV and UPLC-ESI-MS Fingerprints and Analgesic Activities ofVernonia CondensataBaker Extracts

Vernonia condensata Baker leaves have different uses in Brazilian folk medicine, including as analgesic and anti-inflammatory agents. The purpose of this study was to evaluate the seasonal effects on their high performance liquid chromatography with a diode array detector (HPLC-DAD-UV) and ultra-performance liquid chromatography coupled to a mass spectrometer with an electrospray interface (UPLC-ESI-MS) fingerprints, as well as their analgesic activities in mice. There were significant seasonal effects on the relative abundances of the metabolites of the V. condensate leaves as well as on their activities. Analgesic activities in the writhing test were observed with the polar fraction of the leaf extracts collected in autumn, winter and summer (400 mg kg-1); and with the intermediate fraction of leaves collected in autumn (25 and 400 mg kg-1) and in the summer (100 mg kg-1). In conclusion, the results confirm peripherally-mediated anti-inflammatory and analgesic activities for V. condensata leaves and suggest that these are influenced by the harvesting season. N-oxides alkaloids as well as vernonioside play important roles in determining this activity.

Antinociceptive activity of Ligusticum porteri preparations and compounds

Context: The roots and rhizomes of Ligusticum porteri Coulter & Rose (Apiaceae) are widely used in Mexican folk medicine for several purposes, including painful complaints.Objective: The main goal of this work was to demonstrate the analgesic action in mice of some preparations and major compounds from L. porteri.Materials and methods: The extracts, aqueous (AE) and organic (OE), the essential oil (EO) and major compounds (10–316 mg/kg) from L. porteri were evaluated as potential antinociceptive agents using the acetic acid-induced writhing and hot plate tests in ICR mice.Results: All preparations tested exhibited significant antinociceptive effect in the two animal pain models selected. AE and EO were more effective in the writhing test while OE had a better effect in the hot-plate model. On the other hand, Z-ligustilide (1) provoked an increment in the latency period to the thermal stimuli in the hot-plate test at a dose of 31.6 mg/kg, and a decrease in the number of abdominal writhes at 10 mg/kg. Z-3-butylidenephthalide (2) induced a dose-dependent antinociceptive action in the hot-plate assay; this compound was also effective for controlling the pain provoked by chemical irritation at the doses of 10 and 31.6 mg/kg. Finally, diligustilide (3) inhibited the number of writhing responses at all doses tested but was inactive in the hot-plate model.Conclusion: The present investigation provides in vivo evidence supporting the use of L. porteri to treat painful conditions in folk medicine.

Screening of cetirizine for analgesic activity in mice

Background: Pain is the most common symptom for which patients approach doctors. We have multitude of drugs for pain relief, but they have serious side effects ranging from peptic ulcer (e.g. NSAIDs) to renal failure. The other group, opioids have well known side effects ranging from sedation to drug dependence. So a search for a drug for analgesia with high therapeutic effect and fewer side effects will be a boon for the patients. The objective of this study was to find whether cetirizine, a second generation antihistaminic drug, has got any analgesic activity in mice. Methods: Ten adult albino mice weighing 20-30 grams of either sex were randomized to two groups ( n =5). Group I: control group (Treated with solvent 0.1 ml/kg), Group II: Test group (Cetirizine 1mg/kg). All drugs were given orally. The analgesic activity was evaluated by using tail flick, tail immersion and tail clip methods. Reaction time of animals to pain sensation before and after Cetirizine administration were noted at 0, 15, 30, 60 and 90 minutes time intervals respectively on Day 1, 3, 5, 7, 10. Results: Mean reaction time was expressed as Mean±SEM, and one way ANOVA was used to assess statistical significance. Cetirizine was found to have statistically significant analgesic effect in mice and time dependent increase in analgesic effect were observed in all three pain models and maximum analgesic activity was observed at 60 minutes ( p <0.001) after drug administration. Conclusions: Through this study, Cetirizine, a second generation antihistamine, is found to have significant analgesic activity in mice. This effect has to be studied further elaborately in animals as well as in humans.

ACUTE CENTRAL AND PERIPHERAL ANALGESIC ACTIVITY OF ETHANOLIC EXTRACT OF THE LEAVES OF CLERODENDRUM VISCOSUM (EECV) IN RODENT MODELS

Pain, inflammation and pyrexia are the most common disturbing symptom a person experiences in life. Numerous drugs are available in the market for relieving these symptoms and which are sold over the counter. However they have high tendency of having adverse drug reaction from a trivial nausea and vomiting to gastric irritation leading to peptic ulcer, perforation and even death. The aim of the study was to investigate the acute peripheral activity of Ethanolic Extract of the leaves of Clerodendrum viscosum (EECV) by acetic acid induced writhing reflex test in mice and acute central analgesic activity by tail immersion method in rats. Dried powdered leaves of Clerodendrum viscosum were subjected to solvent extraction by using 90 % ethanol. Based on acute oral toxicity study according to Organization for Economic Cooperation and Development (OECD) guidelines No. 423, three doses of the test drug was selected (100, 200 & 400mg/kg for mice) and (75, 150 & 300 mg/kg for rats), and were subjected to acute analgesic activity. The Ethanolic Extract of the leaves of Clerodendrum viscosum (EECV) showed significant (p<0.01) acute peripheral analgesic activity in mice in the dose of 200 mg / kg as compared to control but failed to show any central analgesic activity by tail immersion method at any of the three doses selected compared to control in rats.

Anti-Inflammatory and Analgesic Activity of Total Flavone of Cunninghamia lanceolata

The present study was undertaken to investigate the anti-inflammatory and analgesic activity of total flavone of branches and leaves of Cunninghamia lanceolata (TFC) to provide a scientific basis for its clinical use and resource development. TFC was evaluated for anti-inflammatory and analgesic activity in mice or rats using chemical and thermal models of nociception, including acetic acid-induced writhing test, hot plate latency test, formalin test and carrageenan induced paw oedema test. Results showed that TFC given orally can significantly attenuate acetic acid-induced writhing in mice in a dose-dependent manner. In the hot plate latency test, TFC showed common activity in prolonging duration time only at the highest dose (400 mg/kg). Each dose of TFC could not significantly inhibit the first phase but was active in the later phase of formalin-induced pain, whereas morphine showed notable activity in the two phases. In the carrageenan-induced paw oedema model, TFC could significantly and dose-dependently reduce the carrageenan-induced paw edema at the third and fifth hour, and decrease the content of PEG2 in paw edema tissue and that of COX-2 in blood serum. It may be concluded that TFC showed both anti-inflammatory and analgesic effects, showing that it can be of importance in drug development, especially in the field of pain and inflammation.

The analgesic activity and possible mechanisms of deacetyl asperulosidic acid methyl ester from Ji shi teng in mice

Deacetyl Asperulosidic Acid Methyl Ester (DAAME) from Ji shi teng was evaluated on analgesic activity in mice using chemical and thermal models of nociception. Given intraperitoneally, DAAME, at doses of 40 and 80mg/kg, produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid, subplantar formalin/capsaicin injections and on thermal nociception in the tail-flick test and in the hot plate test. In the open-field test and the rotarod test, DAAME couldn't impair the motor performance, indicating that the observed antinociception was unlikely due to motor abnormality. In a measurement of core body temperature, DAAME (80mg/kg) did not affect temperature within 80min. Moreover, DAAME-induced antinociception in the capsaicin test and the hot plate test was significantly antagonized by glibenclamide. The results suggested that DAAME-produced antinociception was possibly involved in the ATP sensitive K+ channels in the capsaicin test and the hot plate test, which merited exploring further.

Thiazolo[3,2-b]-1,2,4-triazole-5(6H)-one substituted with ibuprofen: Novel non-steroidal anti-inflammatory agents with favorable gastrointestinal tolerance

In an effort to establish new candidates with improved analgesic and anti-inflammatory activities and lower ulcerogenic risk, a series of thiazolo[3,2-b]-1,2,4-triazole-5(6H)-one derivatives of ibuprofen were synthesized. All compounds were evaluated for their in vivo anti-inflammatory and analgesic activities in mice. Furthermore, the ulcerogenic risks of the compounds were determined. In general, none of the compounds represent a risk for developing stomach injury as much as observed in the reference drugs ibuprofen and indomethacin. The compounds carrying a 3-phenyl-2-propenylidene (1a), (biphenyl-4-yl)methylidene (1f) and (1-methylpyrrol-2-yl)methylidene (1n) at the 6th position of the fused ring have been evaluated as potential analgesic/anti-inflammatory agents without a gastrointestinal side effect. These new compounds, therefore, deserve further attention to develop new lead drugs.

양식산 녹조류 청각(Codium fragile) 추출물의 항염증, 해열 및 진통에 대한 생체활성

Dichloromethane, ethanol, and boiling water extracts of the green seaweed Codium fragile, used as an herbal medicine and known as an invasive species over the world, were examined for anti-inflammatory, antipyretic, and analgesic activities in mice. The dichloromethane and ethanol extracts inhibited inflammatory symptoms of mouse ear edema and erythema by 74% or higher. The extracts also demonstrated inhibition of pyrexia, similar to that of acetyl salicylic acid. Eicosapentaenoic acid was isolated from the seaweed as the main active anti-inflammatory compound. These findings are consistent with various claims that the seaweed can be used as remedies for inflammation-related symptoms.

Synthesis and analgesic activity of some novel 2-substituted 1,3,4-thiadiazolo

An ecofriendly synthesis for 1,2,3,4,5,6,8-octahydro- 3-amino-2-thioxo-benzothieno[2,3-d]pyrimidin-4-one (7A, B) has been developed. A series of hitherto unreported compounds (2a-i, 3a-c) have been synthesized by treating 3-Amino-2-mercaptopyrimidinones (7A, B) with one carbon donors like chloroacetyl chloride or chloroacetic acid and subsequently replacing the chloro group by various nucleophiles. Compound 2f was successfully synthesized by an alternate route. All the new compounds were characterized by elemental and spectral analyses. They were screened for analgesic activity in mice. Compounds 2a, b, 3a, b, and 2e, showed very good activity.

Studies on new cyclic imides obtained from aminophenazone with analgesic properties. Potent effects of a 3,4-dichloromaleimide derivative.

This paper describes the synthesis of new cyclic imides obtained by reaction with aminophenazone (CAS 58-15-1, 4-aminoantipyrine) and different anhydrides with further cyclization with acetic acid under reflux. Their structures were confirmed by spectral data (IR and NMR) and elemental analysis. The analgesic activity of the synthesized compounds was investigated initially with the writhing test in mice and the most promising compound, a 3,4-dichloromaleimide derivative (3), was analyzed using other models of nociception. The results indicated that compound 3 exerts potent analgesic activity in mice, being more active than some reference drugs. The analgesia caused by this compound was not reversed by naloxone in the writhing test. In the hotplate test, compound 3 did not increase the latency period of pain induced by thermal stimuli, confirming that it does not interact with opioid systems.

Rhododendrin, an analgesic/anti-inflammatory arylbutanoid glycoside, from the leaves of Rhododendron aureum

To identify an analgesic/anti-inflammatory component from the leaves of Rhododendron aureum (Ericaceae), phytochemical isolation and pharmacological assays (writhing assays and vascular permeability assay for analgesic action in mice; carrageenan-induced paw edemaand TPA-induced ear edema assays of anti-inflammatory action in rats) were performed. Four compounds were isolated from the active fraction (BuOH fraction) by silica gel column chromatography and identified as (-)-rhododendrol, (-)-rhododendrin, avicularin and hyperoside by spectroscopic methods. Rhododendrin, the main compound of the BuOH fraction, exhibited significant analgesic actions in mice and anti-inflammatory actions in rats. This compound accounted for 3.1% of the MeOH extract and 0.48% of dried leaves, respectively, on HPLC analysis. These results suggest that rhododendrin is the major biologically active substance in the leaves of R. aureum with analgesic/anti-inflammatory activity.

AHR-15010—A Novel Anti-arthritic Agent

AHR-15010 (3-(2-methoxyphenoxy)-1,2-propanediol bissulphamate ester) is a compound of novel structure that displays anti-arthritic activity in adjuvant arthritis in rats. When given orally from days 18 through day 50, (excluding weekends) after adjuvant injection, AHR-15010, at doses of 3.16 to 100 mg kg-1, produced significant anti-inflammatory activity and reduced the severity of the hind paw joint lesions as monitored by X-ray analysis. AHR-15010, however, has no acute anti-inflammatory activity in the Evans Blue-carrageenan pleural effusion assay in rats, has no analgesic activity in mice, and has no activity in a classic, delayed-type, hypersensitivity assay in mice or in a cotton pellet granuloma test in rats. These data, in conjunction with biochemical data showing that AHR-15010 has no prostaglandin synthetase inhibiting activity suggest that AHR-15010 is an anti-arthritic with a unique mechanism of action. AHR-15010 is a carbonic anhydrase inhibitor. Data are presented that suggest that AHR-15010 and acetazolamide, a prototype carbonic anhydrase inhibitor, may present novel approaches to the treatment of arthritis.

Analgesic properties of 4-ethoxycarbonyl-1-(2-hydroxy-3-phenoxypropyl) 4-phenylpiperidine (B.D.H. 20) and some related compounds.

Abstract Twenty-one 3-aryloxy or 3-alkoxy-2-hydroxy-n-propyl derivatives of norpethidine were tested subcutaneously for analgesic activity in mice. Many of them are more potent than pethidine. The 2-hydroxy-3-phenoxypropyl derivative (B.D.H. 200) is at least three times more active than morphine and ten times more active than pethidine in this species with a therapeutic index slightly better than morphine and very much better than pethidine. The duration of analgesia is similar to morphine and pethidine and it is less constipating than pethidine. Its effects on respiration and the cardiovascular systems are counteracted by nalorphine. The decrease in activity after oral administration is probably due to a more rapid metabolic breakdown than poor absorption, as this decrease in activity can be modified by pretreatment with iproniazid and BAL while subcutaneous administration is unaffected.

Alpha- and beta-prodine type compounds: configurational studies.

Abstract The addition of various lithium aryl compounds to 1:3-dimethyl-4-piperidone is investigated. Those stereoisomers present as the major proportion of the respective stereoisomeric mixtures are shown to have similar infra-red absorption characteristics which are different from those exhibited by those isomers formed in minor amount. The stereochemistry of addition to 6-membered alicyclic and heterocyclic ketones is discussed; on the basis of these discussions, and the rates of hydrolysis of appropriate esters, the above isomers formed in major amount are allocated the trans (Me/Ar) configuration. The analgesic activities in mice of various stereoisomeric amino-alcohols and esters are given.

Serum and brain concentrations of pentazocine in relation to analgesic activity in mice

Abstract Serum and brain concentrations of pentazocine and its metabolite, the trans-alcohol, have been studied in mice and related to analgesic activity. The concentrations were determined fluorometrically after extraction and isolation of the compounds by partition chromatography as ion pairs. The acute intravenous toxicity (LD50) of the drug was also determined. The analgesic activity was found to reside in the unchanged pentazocine since, after the initial distribution phase, the drug elicits a higher degree of analgesia in animals showing higher brain concentrations of pentazocine. Furthermore, animals which did not show an analgesic response had higher serum concentrations of the trans-alcohol in comparison with animals showing analgesic activity, indicating a relation between analgesia and the degree of metabolism. However, the relation between the analgesic response and the brain concentration during the first 20 min after intravenous injection of the drug was poor.

Dihydroetorphine is a mu-receptor-selective ligand.

The selectivity to opioid receptors of dihydroetorphine, a potent analgesic with only mild physical dependence, was investigated using radioligand binding assay and its analgesic activity in mice determined. The relative affinity ratio of dihydroetorphine to mu-, delta- and kappa- opioid receptors was 333:1:1. The analgesic effect of intracerebro-ventricular injection in mice could be antagonized by the mu-antagonist beta-funaltrexamine but could not be antagonized by delta- and kappa-selective antagonists naltrindole and norbinaltorphimine. We conclude that dihydroetorphine is a selective ligand for the mu-opioid receptor.

Synthesis of New Succinimides and Sulphonated Derivatives with Analgesic Action in Mice

Recently, we have investigated the chemistry and biology of cyclic imides and have used phyllanthimide to obtain several analogues such as maleimides, succinimides and related compounds, which have demonstrated analgesic activity, amongst other properties. The work presented here describes the synthesis of new succinimides and their sulphonated derivatives. These substances were confirmed as having analgesic activity through abdominal constriction tests in mice. The results showed that some of the compounds, given intraperitoneally at a dose of 10 mg kg−1, were more effective than aspirin and paracetamol.

Novel Helix-Constrained Nociceptin Derivatives Are Potent Agonists and Antagonists of ERK Phosphorylation and Thermal Analgesia in Mice

The nociceptin opioid peptide receptor (NOP, NOR, ORL-1) is a GPCR that recognizes nociceptin, a 17-residue peptide hormone. Nociceptin regulates pain transmission, learning, memory, anxiety, locomotion, cardiovascular and respiratory stress, food intake, and immunity. Nociceptin was constrained using an optimized helix-inducing cyclization strategy to produce the most potent NOP agonist (EC50 = 40 pM) and antagonist (IC50 = 7.5 nM) known. Alpha helical structures were measured in water by CD and 2D (1)H NMR spectroscopy. Agonist and antagonist potencies, evaluated by ERK phosphorylation in mouse neuroblastoma cells natively expressing NOR, increased 20-fold and 5-fold, respectively, over nociceptin. Helix-constrained peptides with key amino acid substitutions had much higher in vitro activity, serum stability, and thermal analgesic activity in mice, without cytotoxicity. The most potent agonist increased hot plate contact time from seconds up to 60 min; the antagonist prevented this effect. Such helix-constrained peptides may be valuable physiological probes and therapeutics for treating some forms of pain.