Analgesic Activity Research Articles

Synthetic Transformations of Higher Terpenoids. 45#. Regioselective Synthesis of 5-Labdanoid-Substituted Pyrazoles and Assessment of Their Analgesic Activity

Synthetic Transformations of Higher Terpenoids. 45#. Regioselective Synthesis of 5-Labdanoid-Substituted Pyrazoles and Assessment of Their Analgesic Activity

Antinociceptive and Anti-Inflammatory Activities of Acetonic Extract from Bougainvillea x buttiana (var. Rose).

Background:Bougainvillea x buttiana is an ornamental plant with antioxidant, anti-inflammatory, and cytotoxic activities, which has been traditionally used to treat respiratory diseases. This study aimed to investigate whether the acetonic extract of Bougainvillea x buttiana var. Rose (BxbRAE-100%) has analgesic and anti-inflammatory properties and its potential action mechanisms. Methods: Analgesic and anti-inflammatory activities were evaluated using three murine pain models and two acute inflammation models. In vitro, the ability of the extract to inhibit proteolytic activity and the activities of the enzymes phospholipase A2 (PLA2) and cyclooxygenase (COX) were evaluated. In silico analysis was performed to predict the physicochemical and Absorption, distribution, metabolism, and excretion (ADME) profiles of the compounds previously identified in BxbRAE-100%. Results: In vivo BxbRAE-100% decreased the nociceptive behaviors in the writhing model, the tail immersion, and the formalin test, suggesting that the extract has the potential to relieve pain at peripheral and central levels. Additionally, topical or oral BxbRAE-100% treatment reduced dose-dependent 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced ear inflammation and carrageenan-induced paw edema, respectively. In vitro, BxbRAE-100% significantly inhibited proteolytic activity and PLA2, COX-1 and COX-2 activities. In silico, the compounds previously identified in BxbRAE-100% met Lipinski's rule of five and showed adequate ADME properties. Conclusions: These results support the use of B. x buttiana in Traditional Mexican Medicine and highlight its potential for the development of new treatments for pain and inflammation.

Investigation of Anti-inflammatory, Antipyretic and Analgesic Activities of Citrullus colocynthis in Albino Rats through in vivo and Pharmacoinformatics Studies.

Hyperpyrexia, algesia and inflammation are pathological disorders which are treated with synthetic as well as herbal medications. The basic aim of the present study is to evaluate the ethnopharmacological activities of phytoconstituents that are present in C. colocynthis (fruit extract) by using in vivo and in silico studies. Thirty-six albino rats were used in our studies with an average weight between 150-170 g. Anti-inflammatory activity was investigated using carrageenan (an extract from a red seaweed) that induced edema in albino rat paws. However, in antipyretic and analgesic activity studies, yeast and acetic acid were used to cause pyrexia or algesia, respectively. Different doses of acetone fruit extract were used to treat inflammation, pyrexia and algesia. Our results showed that the maximum percentage inhibition of acetonic fruit extract in anti-inflammatory and analgesic activities was observed at 70% and 100%, respectively, with 400 mg/kg doses, and in pyretic activity the maximum inhibitory percentage was 86% with a 100 mg/kg dose. In in silico analysis, we have shown that bioactive compounds (α-spinasterol, ascorbic acid and chlorogenic acid) found in fruit extract have outstanding inhibition properties that involves proteins PTGS2, TLR2 and TRPV4. C. colocynthis fruit extract shows results that are statistically significant (p < 0.005) and comparable to a reference drug. Acetonic fruit extract of C. colocynthis can be used as a natural and safe remedy with no side effects. Both in vivo and in silico studies on chlorogenic acid, ascorbic acid and α-spinasterol have shown that these are inhibitory compounds that can be used for boosting the immune response.

Phytochemical and Pharmacological Profile of Desmodium gangeticum (L.) DC.: A Comprehensive Review

Abstract: Desmodium gangeticum (L.) DC., commonly known as Shalparni in Ayurveda, has been used for treating various diseases. The plant is one among ten ingredients of classical Ayurvedic formulations Dasamula. Decoctions of root and leaf, root powder and leaf juice of D. gangeticum are used as tonics, febrifuge, digestive, antiemetic, astringent, anti-asthmatic, anti-diarrhoeal and anti-inflammatory agents in traditional medicinal practices of India and its neighbouring countries. Phytochemical investigations of this plant revealed the presence of many bioactive phytoconstituents. The present review was prepared with the objective of documenting the phytochemical and pharmacological profiles of D. gangeticum. The data presented here were collected from various sources like books, journals, various online databases, and monographs and internet search engines Google Scholar, PubMed, Science Direct, etc. Studies reported from phytochemical screening revealed that D. Gangeticum leaves and roots are rich in flavonoids, alkaloids, terpenoids, tannins, phenols, carbohydrates, steroids, phenylpropanoids, pterocarpans, coumarins, and volatile oil. Among the isolated compounds, major bio-active constituents are alkaloids, flavonoids and pterocarpans. All these phytochemicals are widely distributed in various parts of D. gangeticum. The other active constituents like desmodin, hordenine and gangetin are largely responsible for its broad spectrum of therapeutic potentiality. Desmodin belongs to the class of pterocarpans and is reported to have antifungal and antibacterial activities. Gangetin, which also belongs to the pterocarpans, is reported to have anti-inflammatory and analgesic effects. FTIR spectroscopy showed that D. gangeticum extracts are mainly rich in phenolic derivatives. Scientific experiments carried out in vitro as well as preclinical animal experimentations, showed that the plant and its bioactive chemicals exhibit various therapeutic activities. It is reported that D. gangeticum extracts showed potent antioxidant, antibacterial, hypoglycaemic, analgesic, hepatoprotective, anti-inflammatory and antiarthritic activities. Studies reported that D. gangeticum or its formulations are safe when used in appropriate therapeutic dosage.

Wide-ranging Study on Synthesis and Biological Evaluation of 1, 2, 3-triazole

Abstract: 1, 2, 3-Traizole is five-membered heterocyclic compounds having three nitrogen at 1, 2 and 3 positions. 1, 2, 3-Triazoles are important five-membered heterocyclic scaffolds due to their widespread biological activities. 1, 2, 3-Triazole derivative can be readily obtained in good to excellent yields through click chemistry, 1, 3-dipolar cycloaddition, Metal Catalysed azide-alyne cycloaddition method. 1, 2, 3-Triazoles showed various biological activities, such as antiinflammatory, anticonvulsant, antineoplastic, antimicrobial, analgesic, antimalarial, antiviral, antiproliferative, and anticancer activities. The objective of this review is to synthesize pharmacological activity of 1,2,3-triazole derivatives documented in recent literature.

Exploration for the opioidergic, GABAergic and histaminergic potentials of synthesized Schiff’s base derivatives: An in-vivo approach

Herein, five Schiff’s base analogs (designated as AK1 to AK5) were synthesized and screened for their analgesic and anti-inflammatory efficacies. All compounds exhibited analgesic activity at selected doses from 45.31 % to 75.75 %, while the standard drug diclofenac sodium produced result as 86.33 %. Compounds AK1, AK3, AK4 and AK5 were found significantly P<0.001 effective at a dose of 25 mg/kg body weight (b.w). Similarly, in tail immersion test the produced percentage activity were in range from 40.19 % to 62.35 %. in which the compounds AK1, AK2, AK4 and AK5 were significantly P<0.01 effective at dose 12.5 mg/kg b.w, while at this dose significance level of efficacy of AK3 was P<0.05. Similarly, at administering doses of 25 mg/kg b.w all compounds were effective with significance level P<0.001, n = 8. Administration of the synthesized Schiff’s bases at the tested doses significantly reduced paw edema as compared to control. Results of paw edema at 3rd hour was significant P<0.001. AK4 and AK5 were subjected to mechanistic approaches by GABAergic, opiodergic and histaminergic pathways. In GABAergic pathway bicuculline caused a partial reversal of writhings responses indicating the involvement of GABA receptors and therefore the tested compounds may have act through GABAergic pathway. The naloxone caused a mild reversal in the tail immersion test and indicated that some other mechanisms are additionally involved in mode of action of these compounds. Additionally a mild response was observed while studying its action involving histaminergic pathway.

Assessment of Acute Toxicity and Analgesic Activity of Organic and Aqueous Fractions from Retama Monosperma Stems

Assessment of Acute Toxicity and Analgesic Activity of Organic and Aqueous Fractions from Retama Monosperma Stems

In silico insights into the design of novel NR2B-selective NMDA receptor antagonists: QSAR modeling, ADME-toxicity predictions, molecular docking, and molecular dynamics investigations

Based on a structural family of thirty-two NR2B-selective N-Methyl-D-Aspartate receptor (NMDAR) antagonists, two phenylpiperazine derivatives labeled C37 and C39 were conceived thanks to molecular modeling techniques, as novel NMDAR inhibitors exhibiting the highest analgesic activities (of pIC50 order) against neuropathic pain, with excellent ADME-toxicity profiles, and good levels of molecular stability towards the targeted protein of NMDA receptor. Initially, the quantitative structure-activity relationships (QSARs) models were developed using multiple linear regression (MLR), partial least square regression (PLSR), multiple non-linear regression (MNLR), and artificial neural network (ANN) techniques, revealing that analgesic activity was strongly correlated with dipole moment, octanol/water partition coefficient, Oxygen mass percentage, electronegativity, and energy of the lowest unoccupied molecular orbital, whose the correlation coefficients of generated models were: 0.860, 0.758, 0.885 and 0.977, respectively. The predictive capacity of each model was evaluated by an external validation with correlation coefficients of 0.703, 0.851, 0.778, and 0.981 respectively, followed by a cross-validation technique with the leave-one-out procedure (CVLOO) with Q2cv of 0.785, more than Y-randomization test, and applicability domain (AD), in addition to Fisher’s and Student’s statistical tests. Thereafter, ten novel molecules were designed based on MLR QSAR model, then predicted with their ADME-Toxicity profiles and subsequently examined for their similarity to the drug candidates. Finally, two of the most active compounds (C37 and C39) were chosen for molecular docking and molecular dynamics (MD) investigations during 100 ns of MD simulation time in complex with the targeted protein of NMDA receptor (5EWJ.pdb).

Assessing Therapeutic Potentials of Catharanthus roseus (L.) G. Don Focusing on Anti-Diabetic, Analgesic and Anti-Diarrheal Activities

Catharanthus roseus, or 'Nayantara' in Bengali, is a perennial flowering herb. This study aimed to evaluate the pharmacological effectiveness of the plant, focusing on its anti-diabetic, peripheral and central analgesic, and antidiarrheal effects. Methanol soluble partition 200 (MSP-200) and 400 (MSP-400) mg/kg body weight were administered for glucose tolerance test (GTT), heat and chemical-induced response tests, sodium thiosulphate induced test, and castor oil induced test, evaluating anti-diabetic, peripheral and central analgesic, and antidiarrheal effects via in-vivo assay in Swiss-Albino mice model. Methanol soluble partition (MSP) at 200 and 400 mg/kg doses significantly reduced the blood glucose levels of mice by 31.00% and 32.97%, respectively (standard 46.24%). In peripheral analgesic activity, MSP-400 (62.82 ± 4.62%) outperformed MSP-200 (50 ± 3.62%) and MSP-200 (p = 0.0001) exhibited statistically significant central analgesic activity. MSP-400 demonstrated potent anti-diarrheal activity (p = 0.0002). The outcomes from this study put forward a cogent argument that C. roseus plant is capable of producing numerous bioactive compounds such as flavonoids, alkaloids, terpenoids, tannins, etc. which requires systematic phytochemical and pharmacological investigations. Bangladesh Pharmaceutical Journal 27(2): 215-222, 2024 (July)

In vitro Antibacterial and in vivo Antinociceptive Activities of Ethyl Acetate Fraction of Dipterocarpus turbinatus Leaves

The study was aimed to assess the antibacterial and analgesic properties of the ethyl acetate extract from the leaves of Dipterocarpus turbinatus. The antibacterial effectiveness of the extract obtained from the leaves of D. turbinatus was evaluated using the disc diffusion method against both positive and negative Gram strains. Furthermore, the analgesic qualities were assessed by doing the formalin-incited paw licking test in mice model. The ethyl acetate fraction demonstrated significant antibacterial activity against all tested microorganisms (Lactobacillus casei, Corynebacterium sp., Bacillus cereus, Staphylococcus aureus, Escherichia coli, Bacillus azotoformans, and Salmonella typhi) at concentrations of 0.1 mg/disc, 0.3 mg/disc, and 0.5 mg/disc using the disc diffusion method. The extract's zone of inhibition measured between 12 and 25 mm was less than the Kanamycin's diameter of 32–36 mm. The analgesic activity of the substance was evaluated in Swiss Albino mice using the tail immersion and formalin test procedures, revealing a modest level of analgesic activity. In the formalin test, the extract had a strong dose-dependent impact at dosages of 200 mg/kg and 400 mg/kg, as shown by a larger inhibition percentage compared to the standard. This result was statistically significant (***p&lt;0.001) when compared to the control group. During the tail immersion test, the extract showed a significant impact at dose 400 mg/kg (**p&lt;0.01). The plant extract has a modest level of antibacterial and analgesic properties. Bangladesh Pharmaceutical Journal 27(2): 207-214, 2024 (July)

Physicochemical Evaluation and Pharmacological Screening of Fernando Adenophylla Steenis Fruits.

The current study aimed to evaluate the physicochemical properties of Fernandoa adenophylla. Powder studies were carried out to estimate the quantitative physicochemical characteristics of the crude drug, including moisture content, ash content, and extractive values. Using a Soxhlet apparatus and different analytical grade solvents, 3 sample extracts of a crude drug were made. To evaluate the potentially toxic nature, an acute oral toxicity study was performed as per OECD guideline no. 423. Sample extracts were tested and analyzed by ANOVA for pharmacological potential (analgesic, antipyretic, and antidiabetic) using Wister-Albino rats. Where physicochemical analysis indicated purity, quality, and presence of organic/inorganic materials in crude drug extracts, no sign of mortality was found up to 2000 mg/kg of body weight of Fernandoa adenophyllas extracts. Analgesic activity was observed in all sample extracts, whereas only chloroform and ethanolic extracts expressed antipyretic and antidiabetic potential. Ethanolic extract was found to be most potent in pharmacological potential as 200 mg/kg extract dose exhibited %age pain inhibition of 55.12 % and reduced body temperature from 39.78±0.03 °C to 37.22±0.02 °C in hyperthermic rats. A decrease in blood glucose levels up to 57.88 % was observed on the 21st day of the treatment with 500 mg/kg ethanolic extract.

Exploration of Analgesic, Anti-Inflammatory, Neuropharmacological and Antidiabetic Activities of Clerodendrum viscosum Root Extract

In the traditional systems of medicine, Clerodendrum viscosum (CV) has important medicinal uses for the treatment of asthma, ulcer, inflammation, pyrexia, diabetes etc. In this study, analgesic, anti-inflammatory, neuropharmacological and antidiabetic effect of root extract of C. viscosum (CV) was investigated. Mice (Swiss albino) of either sex of 25-30 g were distributed into 4 groups as control (normal water), standard (STD), CV 250 mg/kg and CV 500 mg/kg (n=6). Analgesic effect was investigated by acetic acid initiated writhing test, formalin initiated paw licking test and hot plate test. Anti-inflammatory effect was investigated by xylene and croton oil initiated ear edema test and cotton pellet pleurisy test. Pentobarbital mediated sleeping time and hole cross tests were applied to assess neuro-pharmacological activity. Antidiabetic effect was evaluated by in-vitro alpha amylase inhibitory assay. In the acetic acid initiated writhing test, formalin test and hot plate test, the alcoholic extract of root showed significant antinociceptive activity (p&lt;0.01) at 500 mg/kg dose. The test extract lowered inflammation in xylene, croton oil and cotton pellet test which was significant (p&lt;0.001). The 500 mg/kg dose significantly (p&lt;0.001) increased onset time of sleeping and significantly reduced sleeping duration (p&lt;0.01) in sleeping time test. It also showed insignificant effect in hole-cross test. The extract exhibited a good alpha amylase inhibitory potential (IC50=1.24 mg/ml). C. viscosum root exhibited analgesic, anti-inflammatory, antidiabetic as well as CNS stimulant effect in model mice used for experimental purpose. More investigations are needed for the evaluation of such activities as well as the potential of this plant. Bangladesh Pharmaceutical Journal 27(2): 164-174, 2024 (July)

Phyto-pharmacological and computational profiling of Bombax ceiba Linn. Leaves revealed pharmacological properties against oxidation, hyperglycemia, pain, and diarrhea

The present study aimed to conduct phytochemical and pharmacological profiling of methanolic crude extract of leaves of Bombax ceiba Linn. via experimental and computational approaches. Six secondary metabolites were isolated chromatographically, and the structures were elucidated by extensive analyses of high-resolution 1H and 13C NMR data. The separated compounds were characterized as β-sitosterol (1), β-amyrin (2), β-amyrin acetate (3), β-amyrin palmitate (4), β-amyrone (5), and isoscopoletin (6). DPPH free radical scavenging assay, tail-tipping method, writhing assay, and castor oil-induced diarrheal mice methods, respectively, were used to assess the antioxidant, hypoglycemic, analgesic, and anti-diarrheal activities of the leaf extract of B. ceiba plant species. The study observed significant reductions (p < 0.05) in the level of blood glucose at 30, 60, 120, and 180 min following the administration of the crude extracts (200 mg/kg body weight (bw) and 400 mg/kg bw). These reductions occurred in a time-dependent manner. Additionally, both doses of the investigated extracts exhibited significant (p < 0.05) central and peripheral analgesic effects compared to morphine (2 mg/kg bw) and diclofenac sodium (50 mg/kg bw), respectively. Furthermore, the 400 mg/kg bw extract demonstrated anti-diarrheal activity, reducing 54.17 % of diarrheal episodes in mice compared to loperamide with 70.83 % inhibition. The computational investigations yielded results consistent with existing in vivo findings. The results obtained from molecular docking showed that the isolated compounds had a better or comparable binding affinity to the active binding sites of the glutathione reductase enzyme, mu-opioid receptor, cyclooxygenase 2 (COX-2), glucose transporter 3 (GLUT 3), and kappa opioid receptor. These findings may indicate that the compounds isolated from the B. ceiba plant species have antioxidant, analgesic, hypoglycemic, and anti-diarrheal, properties. Consequently, it was inferred that the plant B. ceiba might be beneficial in dealing with oxidation, diarrhea, hyperglycemia, and pain. Nonetheless, further investigations are necessary to perform thorough phytochemical profiling and elucidate the exact mechanistic ways of the crude extract and the isolated phytoconstituents.

German Chamomile (Matricaria chamomilla L.) Flower Extract, Its Amino Acid Preparations and 3D-Printed Dosage Forms: Phytochemical, Pharmacological, Technological, and Molecular Docking Study.

German chamomile (Matricaria chamomilla L.) is an essential oil- containing medicinal plant used worldwide. The aim of this study was to gain knowledge of the phytochemical composition and the analgesic and soporific activity of Matricaria chamomilla L. (German chamomile) flower extract and its amino acid preparations, to predict the mechanisms of their effects by molecular docking and to develop aqueous printing gels and novel 3D-printed oral dosage forms for the flower extracts. In total, 22 polyphenolic compounds and 14 amino acids were identified and quantified in the M. chamomilla extracts. In vivo animal studies with rodents showed that the oral administration of such extracts revealed the potential for treating of sleep disorders and diseases accompanied by pain. Amino acids were found to potentiate these effects. Glycine enhanced the analgesic activity the most, while lysine and β-alanine improved the soporific activity. The molecular docking analysis revealed a high probability of γ-aminobutyric acid type A (GABAA) and N-methyl-D-aspartate (NMDA) receptor antagonism and 5-lipoxygenase (LOX-5) inhibition by the extracts. A polyethylene oxide (PEO)-based gel composition with the M. chamomilla extracts was proposed for preparing a novel 3D-printed dosage form for oral administration. These 3D-printed extract preparations can be used, for example, in dietary supplement applications.

Advancements in Non-Addictive Analgesic Diterpenoid Alkaloid Lappaconitine: A Review.

The perennial herb Aconitum sinomontanum Nakai (Ranunculaceae) has been utilized as a traditional oriental medicine in China for numerous years. The principal pharmacological constituent of A. sinomontanum, lappaconitine (LA), exhibits analgesic, anti-inflammatory, anti-tumor, anti-arrhythmic, and anti-epileptic activities. Due to its potent efficacy and non-addictive nature, LA is widely utilized in the management of cancer pain and postoperative analgesia. This review encompasses the research advancements pertaining to LA including extraction methods, separation techniques, pharmacological properties, chemical modifications, and clinical applications. Additionally, it offers insights into the potential applications and current challenges associated with LA to facilitate future research endeavors.

A Comprehensive Review of Traditional Medicinal Uses, Geographical Distribution, Botanical Characterization, Phytochemistry, and Pharmacology of Aralia continentalis Kitag.

Aralia continentalis Kitag. (A. continentalis) holds significant medicinal value among the Aralia genus. It has traditionally been employed in ethnomedicine to address a wide range of conditions, including wind-cold-dampness arthralgia; rheumatic pain in the waist and lower extremities; lumbar muscular strain; injuries resulting from falls, fractures, contusions, and strains; headache; toothache; and abscesses. Modern pharmacological research has validated its therapeutic potential, encompassing anti-inflammatory, analgesic, antioxidant, antimicrobial, insecticidal, hepatoprotective, anti-diabetic, and cytotoxic properties, among other pharmacological effects. To compile comprehensive knowledge on A. continentalis, a rigorous literature search was undertaken utilizing databases like SciFinder, PubMed, and Web of Science. This review seeks to delve into the plant's traditional applications, geographical distribution, botanical characteristics, phytochemistry, and pharmacology. The objective is to lay a foundation and propose novel research directions for exploring the plant's potential applications. Currently, one hundred and fifty-nine compounds have been isolated and identified from A. continentalis, encompassing diterpenoids, steroids, triterpenoids, volatile components, phenolics, vitamins, trace elements, and other compounds. Notably, diterpenoids, steroids, triterpenoids, volatile components, and phenolics have exhibited pronounced pharmacological effects, such as anti-inflammatory, analgesic, antioxidant, hepatoprotective, antidiabetic, and antimicrobial activities. However, despite the extensive research conducted, further studies are imperative to unravel new components and mechanisms of action, necessitating more in-depth investigations. This comprehensive exploration could pave the way for advancing and harnessing the potential of A. continentalis.

AR71, Histamine H3 Receptor Ligand-In Vitro and In Vivo Evaluation (Anti-Inflammatory Activity, Metabolic Stability, Toxicity, and Analgesic Action).

The future of therapy for neurodegenerative diseases (NDs) relies on new strategies targeting multiple pharmacological pathways. Our research led to obtaining the compound AR71 [(E)-3-(3,4,5-trimethoxyphenyl)-1-(4-(3-(piperidin-1-yl)propoxy)phenyl)prop-2-en-1-one], which has high affinity for human H3R (Ki = 24 nM) and selectivity towards histamine H1 and H4 receptors (Ki > 2500 nM), and showed anti-inflammatory activity in a model of lipopolysaccharide-induced inflammation in BV-2 cells. The presented tests confirmed its antagonist/inverse agonist activity profile and good metabolic stability while docking studies showed the binding mode to histamine H1, H3, and H4 receptors. In in vitro tests, cytotoxicity was evaluated at three cell lines (neuroblastoma, astrocytes, and human peripheral blood mononuclear cells), and a neuroprotective effect was observed in rotenone-induced toxicity. In vivo experiments in a mouse neuropathic pain model demonstrated the highest analgesic effects of AR71 at the dose of 20 mg/kg body weight. Additionally, AR71 showed antiproliferative activity in higher concentrations. These findings suggest the need for further evaluation of AR71's therapeutic potential in treating ND and CNS cancer using animal experimental models.

Analgesic activity of new ligands of the NMDA receptor complex

BACKGROUND: The activation of spinal cord NMDA receptors is a key factor in the pathogenesis of acute and chronic pain. Therefore, the use of existing NMDA antagonists in analgesic schemes and the development of new compounds targeting the NMDA receptor complex are gaining attention. New ligands of the glutamate NMDA receptor complex are derivatives of imidazole-4,5-dicarboxylic acid. The conformational rigidity of the molecules of imidazole-4,5-dicarboxylic acid derivatives allows for increased selectivity of interaction and reduced side effects. AIM: This study aimed to investigate the analgesic effect of new ligands of the glutamate NMDA receptor complex, which are derivatives of imidazole-4,5-dicarboxylic acid, in rats using the tail-flick test and the formalin test. MATERIALS AND METHODS: The analgesic activity of the compounds was examined in a model of acute somatic (thermal) pain in the tail-flick test and model of somatic pain induced by algogens in the formalin test. The tested compounds (IEM-303 and IEM-2044) were administered intraperitoneally at doses of 5, 10, 15, and 20 mg/kg. Мetamizole was used as the comparison drug. RESULTS: The experiments demonstrated a significant dose-dependent analgesic effect of the tested compounds on the experimental models of acute pain at doses of 5–20 mg/kg. The tail-flick latency increased by 1.4–1.7 times in the IEM-2044 and IEM-303 groups compared with the value in the control group. CONCLUSIONS: The analgesic activity of the tested compounds at 10–20 mg/kg doses was comparable to that of metamizole, indicating the prospect of developing these agents and further searching for effective and safe analgesics in this pharmacological class.

Design and Synthesis of sEH/HDAC6 Dual-Targeting Inhibitors for the Treatment of Inflammatory Pain.

Soluble epoxide hydrolase (sEH) and HDAC6 mediate the NF-κB pathway in inflammatory responses, and their inhibitors exhibit powerful anti-inflammatory and analgesic activities in treating both inflammation and pain. Therefore, a series of dual-targeting inhibitors containing urea or squaramide and hydroxamic acid moieties were designed and synthesized, and their role as a new sEH/HDAC6 dual-targeting inhibitor in inflammatory pain was evaluated in a formalin-induced mice model and a xylene-induced mouse ear swelling model. Among them, compounds 28g and 28j showed the best inhibitory and selectivity of sEH and HDAC6. Compound 28g had satisfactory pharmacokinetic characteristics in rats. Following administration at 30 mg/kg, compound 28g exhibited more effective analgesic activity than either an sEH inhibitor (GL-B437) or an HDAC6 inhibitor (Rocilinostat) alone and coadministration of both inhibitors. Thus, these novel sEH/HDAC6 dual-targeting inhibitors exhibited powerful analgesic activity in nociceptive behavior and are worthy of further development.

An experimental evaluation of Anti-Inflammatory and Analgesic Activity of Allium Cepa Linn. and Allium Ascalonicum Linn. - A comparative study

An experimental evaluation of Anti-Inflammatory and Analgesic Activity of Allium Cepa Linn. and Allium Ascalonicum Linn. - A comparative study