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1.
J Anesth Hist ; 6(3): 158-160, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32921487

RESUMO

United Brethren minister Thomas S. McNeil formulated an analgesic nostrum in 1848, most likely from opium, alcohol, ether, and other proprietary ingredients. Massaged on externally as a pain liniment, his so-called pain exterminator could also be mixed in sweetened water and imbibed as an analgesic, antitussive, and antidiarrheal. A familiar antebellum remedy for both Union and Confederate forces in the Civil War, McNeil's Pain Exterminator would be manufactured by McNeil's pastor and then successors, for more than a half-century after McNeil's accidental drowning in 1874.


Assuntos
Analgésicos/história , Panaceia/história , Publicidade/história , Analgésicos/efeitos adversos , Analgésicos/química , Clero/história , História do Século XIX , Humanos , Panaceia/efeitos adversos , Panaceia/química , Estados Unidos
2.
PLoS One ; 15(6): e0234176, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497151

RESUMO

Chronic neuropathic pain (NP) is a growing clinical problem for which effective treatments, aside from non-steroidal anti-inflammatory drugs and opioids, are lacking. Cannabinoids are emerging as potentially promising agents to manage neuroimmune effects associated with nociception. In particular, Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and their combination are being considered as therapeutic alternatives for treatment of NP. This study aimed to examine whether sex affects long-term outcomes on persistent mechanical hypersensitivity 7 weeks after ceasing cannabinoid administration. Clinically relevant low doses of THC, CBD, and a 1:1 combination of THC:CBD extracts, in medium chain triglyceride (MCT) oil, were orally gavaged for 14 consecutive days to age-matched groups of male and female sexually mature Sprague Dawley rats. Treatments commenced one day after surgically inducing a pro-nociceptive state using a peripheral sciatic nerve cuff. The analgesic efficacy of each phytocannabinoid was assessed relative to MCT oil using hind paw mechanical behavioural testing once a week for 9 weeks. In vivo intracellular electrophysiology was recorded at endpoint to characterize soma threshold changes in primary afferent sensory neurons within dorsal root ganglia (DRG) innervated by the affected sciatic nerve. The thymus, spleen, and DRG were collected post-sacrifice and analyzed for long-term effects on markers associated with T lymphocytes at the RNA level using qPCR. Administration of cannabinoids, particularly the 1:1 combination of THC, elicited a sustained mechanical anti-hypersensitive effect in males with persistent peripheral NP, which corresponded to beneficial changes in myelinated Aß mechanoreceptive fibers. Specific immune cell markers associated with T cell differentiation and pro-inflammatory cytokines, previously implicated in repair processes, were differentially up-regulated by cannabinoids in males treated with cannabinoids, but not in females, warranting further investigation into sexual dimorphisms that may underlie treatment outcomes.


Assuntos
Analgésicos/administração & dosagem , Analgésicos/farmacologia , Canabidiol/efeitos adversos , Canabidiol/farmacologia , Dronabinol/administração & dosagem , Dronabinol/farmacologia , Óleos/química , Administração Oral , Analgésicos/química , Animais , Biomarcadores/metabolismo , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Canabidiol/química , Dronabinol/química , Composição de Medicamentos , Interações Medicamentosas , Feminino , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley
3.
BMC Complement Med Ther ; 20(1): 102, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228549

RESUMO

BACKGROUND: Panch phoron is a mixture of five spices containing an equal proportion of Foeniculum vulgare (fennel), Trigonella foenum-graecum Linn (fenugreek), Nigella sativa (black cumin), Cuminum cyminum (cumin) and Brassica nigra (black mustard). The mixture is commonly used in Bangladeshi cuisine and possesses many pharmacological effects. In this study, we evaluated the antinociceptive and anti-inflammatory activities of aqueous panch phoron extract (PPE) in vivo, its possible mechanism of action and phytochemical analysis by High-Performance Liquid Chromatography (HPLC). We also investigated the effect of PPE on postoperative pain in mice. METHODS: HPLC was carried out using LC-20A Modular HPLC system to identify the bioactive compounds present in PPE. Five groups of Swiss albino male mice (n = 6 per group) were orally treated with 10 ml/kg of distilled water or 10 mg/kg of sodium diclofenac or three doses of PPE (100 mg/kg, 300 mg/kg, 500 mg/kg). In vivo assessment was carried out by the writhing test, tail-flick test, formalin test, and carrageenan induced paw edema test. The opioid antagonist, naloxone was used in the acetic acid test to evaluate the involvement of opioid receptors. To assess the effect of PPE in postoperative pain, mice that underwent sciatic nerve surgery were measured for the paw withdrawal latency in a hot water bath. RESULTS: In HPLC analysis, different types of phenolic compounds and flavonoids, including catechin hydrate, para-coumaric acid, vanillic acid, and syringic acid were detected. Treatment with PPE exhibited dose-dependent antinociceptive and anti-inflammatory activities in pain models (p < 0.05). Furthermore, naloxone did not reverse the effect of PPE in the writhing test. Mice that underwent sciatic nerve surgery showed that the paw withdrawal latency increased gradually over 7 days. CONCLUSIONS: Our results demonstrate that PPE has significant antinociceptive and anti-inflammatory activities and can provide significant postoperative analgesia.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Dor Pós-Operatória/tratamento farmacológico , Extratos Vegetais/farmacologia , Especiarias , Analgésicos/química , Animais , Anti-Inflamatórios/química , Bangladesh , Cromatografia Líquida de Alta Pressão , Masculino , Camundongos , Extratos Vegetais/química , Sementes/química
4.
Chem Pharm Bull (Tokyo) ; 68(2): 140-149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32009081

RESUMO

Previously, we reported that the c-Met inhibitory effect of Ephedra Herb extract (EHE) is derived from ingredients besides ephedrine alkaloids. Moreover, analgesic and anti-influenza activities of EHE and ephedrine alkaloids-free Ephedra Herb extract (EFE) have been reported recently. In this study, we examined the fractions containing c-Met kinase inhibitory activity from EHE and the fractions with analgesic and anti-influenza activities from EFE, and elucidated the structural characteristics of the active fractions. Significant c-Met kinase activity was observed in 30, 40, and 50% methanol (MeOH) eluate fractions obtained from water extract of EHE using Diaion HP-20 column chromatography. Similarly, 20 and 40% MeOH, and MeOH eluate fractions obtained from water extract of EFE were found to display analgesic and anti-influenza activities. Reversed phase-HPLC analysis of the active fractions commonly showed broad peaks characteristic of high-molecular mass condensed tannin. The active fractions were analyzed using 13C-NMR and decomposition reactions; the deduced structures of active components were high-molecular mass condensed tannins, which were mainly procyanidin B-type and partly procyanidin A-type, including pyrogallol- and catechol-type flavan 3-ols as extension and terminal units. HPLC and gel permeation chromatography (GPC) analyses estimated that the ratio of pyrogallol- and catechol-type was approximately 9 : 2, and the weight-average molecular weight based on the polystyrene standard was >45000. Furthermore, GPC-based analysis was proposed as the quality evaluation method for high-molecular mass condensed tannin in EHE and EFE.


Assuntos
Ephedra/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Alcaloides/química , Alcaloides/farmacologia , Analgésicos/química , Analgésicos/farmacologia , Animais , Antivirais/química , Antivirais/farmacologia , Biflavonoides/química , Biflavonoides/farmacologia , Catequina/química , Catequina/farmacologia , Linhagem Celular Tumoral , Cães , Efedrina/química , Efedrina/farmacologia , Humanos , Células Madin Darby de Rim Canino , Masculino , Camundongos , Proantocianidinas/química , Proantocianidinas/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores
5.
Chemistry ; 26(13): 2973-2979, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898822

RESUMO

N-Demethylation of oxycodone is one of the key steps in the synthesis of important opioid antagonists like naloxone or analgesics like nalbuphine. The reaction is typically carried out using stoichiometric amounts of toxic and corrosive reagents. Herein, we present a green and scalable organophotocatalytic procedure that accomplishes the N-demethylation step using molecular oxygen as the terminal oxidant and an organic dye (rose bengal) as an effective photocatalyst. Optimization of the reaction conditions under continuous flow conditions using visible-light irradiation led to an efficient, reliable, and scalable process, producing noroxycodone hydrochloride in high isolated yield and purity after a simple workup.


Assuntos
Analgésicos/química , Morfinanos/química , Oxicodona/química , Desmetilação , Humanos
6.
Mater Sci Eng C Mater Biol Appl ; 108: 110194, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923931

RESUMO

The thermal, physical, and morphological properties of diphenhydraminium ibuprofenate ([DIP][IBU]) adsorbed onto mesoporous silica (SiO2-60 Šand SiO2-90 Å) from solution were determined. The thermal, physical, and morphological properties of [DIP][IBU] supported on silica were determined. The adsorption of [DIP][IBU] on the pores and surface of silica was proven by N2 adsorption/desorption isotherms. Additionally, release profiles were determined for all systems, and the antinociceptive activity of neat [DIP][IBU] and [DIP][IBU] supported on silica were determined. The interaction of [DIP][IBU] and silica was dependent on pore size, with the formation of a [DIP][IBU] monolayer on SiO2-60 and a multilayer on SiO2-90. The release profile was sustained and slow and dependent on the pore size of the silica, in which the smaller the pore size, the faster the release. The nociceptive evaluation showed that [DIP][IBU] presents a greater (99.21 ±â€¯0.85%) antinociceptive effect than the ibuprofen (46 ±â€¯4.3%). Additionally, [DIP][IBU] on SiO2-60 (90 ±â€¯5.8%) had a greater antinociceptive effect than on SiO2-90 (73 ±â€¯13.2%), which indicates that in vivo tests are in accordance with the in vitro experiments.


Assuntos
Analgésicos , Ibuprofeno , Dor/tratamento farmacológico , Dióxido de Silício , Analgésicos/química , Analgésicos/farmacocinética , Analgésicos/farmacologia , Animais , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Avaliação Pré-Clínica de Medicamentos , Ibuprofeno/análogos & derivados , Ibuprofeno/química , Ibuprofeno/farmacocinética , Ibuprofeno/farmacologia , Masculino , Camundongos , Dor/metabolismo , Dor/fisiopatologia , Porosidade , Dióxido de Silício/química , Dióxido de Silício/farmacocinética , Dióxido de Silício/farmacologia
7.
Molecules ; 25(2)2020 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-31968561

RESUMO

Kleinia pendula (Forssk.) DC. is a prostrate or pendent dark green succulent herb found in the southwestern mountain regions of Saudi Arabia. The literature survey of the plant reveals a lack of phytochemical and pharmacological studies, although traditional uses have been noted. The objective of the present work was to assess the in vivo analgesic and anti-inflammatory activities, as well as, the in vitro cytotoxic potential of the fractions of Kleinia pendula, and correlate these activities to the plant metabolites. The methanolic extract of Kleinia pendula was subjected to fractionation with n-hexane, ethyl acetate, chloroform, n-butanol, and water. The fractions were screened for their analgesic and anti-inflammatory activities, as well as cytotoxic activity against breast, liver, and colon cancer cell lines. The n-hexane and chloroform fractions of Kleinia pendula showed significant cytotoxic activity against all three cancer cell lines tested. The ethyl acetate and chloroform fractions showed significant analgesic and anti-inflammatory activities. The metabolites in these three active fractions were determined using UPLC-PDA-ESI-MS. Thus, the analgesic and anti-inflammatory activities of the plant were attributed to its phenolic acids (caffeoylquinic acid derivatives, protocatechuic, and chlorogenic acids). While fatty acids and triterpenoids such as (tormentic acid) in the hexane fraction are responsible for the cytotoxic activity; thus, these fractions of Kleinia pendula may be a novel source for the development of new plant-based analgesic, anti-inflammatory, and anticancer drugs.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Fabaceae/química , Compostos Fitoquímicos/farmacologia , Analgésicos/química , Anti-Inflamatórios/química , Antineoplásicos Fitogênicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Células HCT116 , Células Hep G2 , Humanos , Células MCF-7 , Espectrometria de Massas , Compostos Fitoquímicos/química , Extratos Vegetais/química , Arábia Saudita , Senécio
8.
Chin J Nat Med ; 18(1): 28-35, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31955821

RESUMO

Neuropathic pain (NP) has become a serious global health issue and a huge clinical challenge without available effective treatment. P2 receptors family is involved in pain transmission and represents a promising target for pharmacological intervention. Traditional Chinese medicine (TCM) contains multiple components which are effective in targeting different pathological mechanisms involved in NP. Different from traditional analgesics, which target a single pathway, TCMs take the advantage of multiple components and multiple targets, and can significantly improve the efficacy of treatment and contribute to the prediction of the risks of NP. Compounds of TCM acting at nucleotide P2 receptors in neurons and glial cells could be considered as a potential research direction for moderating neuropathic pain. This review summarized the recently published data and highlighted several TCMs that relieved NP by acting at P2 receptors.


Assuntos
Analgésicos/química , Analgésicos/farmacologia , Medicina Tradicional Chinesa , Neuralgia/tratamento farmacológico , Receptores Purinérgicos P2/efeitos dos fármacos , Humanos , Estrutura Molecular
9.
Phytochemistry ; 171: 112234, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901735

RESUMO

A total of fifteen grayanane diterpenoid glucosides including eight undescribed ones, pierisjaponosides A-H, were isolated from the leaves of Pieris japonica (Thunb.) D. Don ex G. Don (Ericaceae). Their structures were established by extensive spectros copic techniques including HRESIMS and NMR, as well as chemical methods. The absolute configurations of pierisjaponosides A, B, and D were finally established by single-crystal X-ray diffraction with Cu Kα radiation. This is the first time to report the crystal structure of a 5,9-epoxygrayanane diterpenoid glucoside. Pierisjaponoside E represents the first example of a 9ß-hydroxygrayan-1(10)-ene diterpenoid. All the isolated grayanane diterpenoid glucosides were evaluated for their analgesic activities in the acetic acid-induced writhing models in mice, and showed significant analgesic effects. Pierisjaponosides A and C-H, micranthanoside A, pieroside A, and craiobiosides A and B displayed significant analgesic effects with the writhe inhibition rates over 50% at a dose of 5.0 mg/kg. Pierisjaponoside E exhibited significant analgesic activities with the percentage inhibitions of 81.7%, 70.4%, and 52.1% at the doses of 5.0, 1.0, and 0.2 mg/kg, respectively. The preliminary structure-activity relationships of grayanane diterpenoid glucosides as potent analgesics were discussed, giving some clues to design novel analgesics.


Assuntos
Analgésicos/uso terapêutico , Diterpenos/uso terapêutico , Ericaceae/química , Glucosídeos/uso terapêutico , Dor/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Ácido Acético , Analgésicos/química , Analgésicos/isolamento & purificação , Animais , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Feminino , Glucosídeos/química , Glucosídeos/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos , Modelos Moleculares , Estrutura Molecular , Dor/induzido quimicamente , Medição da Dor , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Folhas de Planta/química , Relação Estrutura-Atividade
10.
Eur J Med Chem ; 186: 111902, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31771828

RESUMO

We recently identified novel small-molecule antagonists of the PACAP type I (PAC1) receptor using docking-based in silico screening followed by in vitro/vivo pharmacological assays. In the present study, we synthesized 18 novel derivatives based on the structure of PA-9, a recently developed antagonist of the PAC1 receptor, with a view to obtain a panel of compounds with more potent antagonistic and analgesic activities. Among them, compound 3d showed improved antagonistic activities. Intrathecal injection of 3d inhibited both pituitary adenylate cyclase-activating polypeptide (PACAP) and spinal nerve ligation-induced mechanical allodynia. The effects were more potent than PA-9. Compound 3d also showed anti-allodynic effects following oral administration. Hence, our results suggest that 3d may become an orally available analgesic in the treatment of the neuropathic pain.


Assuntos
Analgésicos/farmacologia , Neuralgia/tratamento farmacológico , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/farmacologia , Analgésicos/síntese química , Analgésicos/química , Animais , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos , Estrutura Molecular , Neuralgia/metabolismo , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-Atividade
11.
Eur J Med Chem ; 187: 111917, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31806536

RESUMO

Mechanical Allodynia (MA), a frequent chronic pain symptom caused by innocuous stimuli, constitutes an unmet medical need, as treatments using analgesics available today are not always effective and can be associated with important side-effects. A series of 3,5-disubstituted pyridin-2(1H)-ones was designed, synthesized and evaluated in vivo toward a rat model of inflammatory MA. We found that the series rapidly and strongly prevented the development of MA. 3-(2-Bromophenyl)-5-(phenylamino)pyridin-2(1H)-one 69, the most active compound of the series, was also able to quickly reverse neuropathic MA in rats. Next, when 69 was evaluated toward a panel of 50 protein kinases (PK) in order to identify its potential biological target(s), we found that 69 is a p38α MAPK inhibitor, a PK known to contribute to pain hypersensitivity in animal models. 3,5-Disubstituted pyridin-2(1H)-ones thus could represent a novel class of analgesic for the treatment of MA.


Assuntos
Analgésicos/uso terapêutico , Hiperalgesia/tratamento farmacológico , Piridonas/uso terapêutico , Analgésicos/síntese química , Analgésicos/química , Animais , Relação Dose-Resposta a Droga , Estrutura Molecular , Medição da Dor , Piridonas/síntese química , Piridonas/química , Ratos , Relação Estrutura-Atividade
12.
Eur J Med Chem ; 186: 111911, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31791644

RESUMO

Antipyrine (1,2-dihydro-1,5-dimethyl-2-phenylpyrazole-3-one) in a structural frame consists of a five membered lactam pyrazolone heterocyclic ring as a pharmacophore moiety. It is evident from literature that the molecules having nitrogen bearing heterocyclic nuclei clearly exhibit several biological actions. Commercially available pyrazolone derivatives as drugs, analgin and metamizol are an established chemical class of analgesics. Recent trends of synthetic routes and several biological actions of antipyrine analogues are considered in this review. Indeed, the synthesized derivatives possess antipyrine moiety having versatile biological properties, antimicrobial, antitubercular, anthelmintic, antioxidant, analgesic, anti-inflammatory, cytotoxic and antiviral activities.


Assuntos
Analgésicos/farmacologia , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Antituberculosos/farmacologia , Analgésicos/química , Animais , Anti-Infecciosos/química , Anti-Inflamatórios/química , Antineoplásicos/química , Antipirina/química , Antipirina/farmacologia , Antituberculosos/química , Humanos , Pirazolonas/química , Pirazolonas/farmacologia
13.
J Photochem Photobiol B ; 202: 111668, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31734435

RESUMO

Fraxinus rhynchophylla belongs to the family of Oleaceae and also called as Chinese ash wood possesses various pharmacological properties such as neuroprotective, antimicrobial, anti-inflammatory, etc. Therefore we synthesized ZnO nanoparticles using Fraxinus rhynchophylla wood extract as reducing and capping agent. The synthesized nanoparticles were characterized with the aid of UV-Spec, DLS, FT-IR and TEM analysis. Green synthesized ZnO nanoparticles were then assessed for anti-nociceptive property by using various nociception models such as thermal stress-induced, acetic acid, glutamate, capsaicin, and formalin-induced nociception. The sedative effect of synthesized ZnO nanoparticles was evaluated with an open field test. UV-Spectroscopic analysis confirms the formation of ZnO nanoparticles and the characterization studies DLS, FT-IR, and TEM analysis prove it has ideal nanoparticle can be used as a nano-drug. Results of both thermal stress-induced methods hot plate and tail immersion nociception test verified the synthesized ZnO nanoparticles are a potent antinociceptive drug. ZnO nanoparticles effectively reduced the abdominal writhes in acetic acid-induced nociception and it also significantly decreased the nociception activity in another glutamate, capsaicin, and formalin-induced nociception models. Open field experiment proved that synthesized ZnO nanoparticles are less sedative compared to the standard antinociceptive drug morphine. Overall our findings authentically confirm ZnO nanoparticles synthesized from Fraxinus rhynchophylla wood extract is a novel drug that persuasively reduces nociception in different nociceptive induced mice models and can be the best alternative for allopathic drugs which renders severe side effects.


Assuntos
Analgésicos/uso terapêutico , Fraxinus/química , Nanopartículas Metálicas/química , Dor/tratamento farmacológico , Óxido de Zinco/química , Analgésicos/síntese química , Analgésicos/química , Animais , Modelos Animais de Doenças , Formaldeído/toxicidade , Fraxinus/metabolismo , Química Verde , Temperatura Alta , Masculino , Nanopartículas Metálicas/uso terapêutico , Camundongos , Dor/induzido quimicamente , Casca de Planta/química , Casca de Planta/metabolismo , Extratos Vegetais/química
14.
Nat Prod Res ; 34(7): 1041-1045, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30580603

RESUMO

The pollen of T. angustifolia, also known as Pu huang in Chinese, has been used for treatment of stranguria, hematuria, dysmenorrhea, metrorrhagia and injuries in China for a long time. Extensive efforts have been directed toward its phytochemical and biological aspects. However, little is known about its anti-nociceptive implication and material basis. This work presented the investigation of the anti-nociceptive effect of Typhae Pollen using an effect-directed fractionation strategy, thereby leading to identification of isorhamnetin-3-O-neohesperidin (1) and typhaneoside (2), together with other minor flavonoid glycoside congeners, as the main anti-nociceptive constituents. This work not only unveils the anti-nociceptive potential of Typhae Pollen, but also establishes a method to enrich and identify the anti-nociceptive constitutes of Typhae Pollen. Moreover, this work is a successful example of effect-directed fractionation strategy, which represents a powerful tool in TCM-based drug discovery and development.


Assuntos
Analgésicos/isolamento & purificação , Flavonoides/farmacologia , Pólen/química , Typhaceae/química , Analgésicos/química , Animais , Fracionamento Químico/métodos , China , Medicamentos de Ervas Chinesas , Flavonoides/química , Flavonoides/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia
15.
J Ethnopharmacol ; 247: 112265, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31580941

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hymenaea cangaceira Pinto, Mansano & Azevedo (Fabaceae) is a Brazilian medicinal plant widely known as "Jatobá". In folk medicine, it is used to treat infections, respiratory problems, rheumatism, antitumoral, inflammation and pain, however, no activity has been scientifically validated. AIM OF THE STUDY: This study investigated chemical composition of essential oil from Hymenaea cangaceira (EOHc), antimicrobial, antinociceptive and antioxidant activities besides protection against DNA damage and hemolysis. MATERIAL AND METHODS: The essential oil was obtained by hydrodistillation, and characterized by GC-MS and GC-FID. The evaluation of antimicrobial activity was performed by microdilution method. The evaluation of the antioxidant activity was performed using the radicals DPPH, ABTS, O2- and OH-, and the protection of DNA damage using plasmid pBR322. Different experimental models were used to evaluate the antinociceptive effect (acetic acid and formalin), and evaluate the mechanisms of action involved with pharmacological antagonists (naloxone, atropine and gibenclamide) in mice. The essential oil was evaluated for hemolysis on human erythrocytes. RESULTS: The extraction of EOHc showed a yield of 0.18% on a dry basis, presenting high content of hydrocarbon sesquiterpenes (79.04%), high antioxidant activity and protect DNA from damage, besides presenting antifungal and antibacterial activity against Gram-positive and Gram-negative bacteria in vitro. It was found that the essential oil had no acute toxicity in mice up to 5000 mg/kg oral administration (o.a.), in addition to no hemolysis on human erythrocytes. The reduction of antinociceptive activity was 75%, with the opioid system as the mechanism of action. CONCLUSION: Our results validate the main activities by the traditional use attributed to H. cangaceira for antimicrobial and analgesic activity. In addition, the oil has a potent antioxidant activity, protecting the body against oxidative stress damage, adding new value to an endemic species not known to the industry.


Assuntos
Analgésicos/farmacologia , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Hymenaea/química , Óleos Voláteis/farmacologia , Óleos Vegetais/farmacologia , Ácido Acético/toxicidade , Analgésicos/química , Analgésicos/isolamento & purificação , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Brasil , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Etanol/química , Etnofarmacologia , Formaldeído/toxicidade , Humanos , Medicina Tradicional/métodos , Camundongos , Testes de Sensibilidade Microbiana , Nociceptividade/efeitos dos fármacos , Óleos Voláteis/química , Óleos Voláteis/uso terapêutico , Dor/induzido quimicamente , Dor/diagnóstico , Dor/tratamento farmacológico , Medição da Dor , Óleos Vegetais/química , Óleos Vegetais/isolamento & purificação , Testes de Toxicidade Aguda
16.
J Pharm Biomed Anal ; 178: 112900, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31629973

RESUMO

PURPOSE: Gabapentin is degraded directly into a high toxicity form known as gabapentin lactam (gaba-L) with a maximizing desire in mild pH and low humidity. This study reports the lactamization process of gabapentin, along with a detailed analysis of the energy landscape, geometry, and thermodynamic and kinetic preference of the process. To investigate the effect of the acidic/basic conditions on the energy landscape, the energy profiles were investigated for both protonation and deprotonation forms of gabapentin. METHODS: All the calculations were performed by using the density functional theory (DFT) and the G4MP2 levels of theory in the conductor-like polarizable continuum model, CPCM, and water as the solvent. RESULTS: The lactamization process is an intramolecular cyclization which results in formation of gabapentin-lactam. The chemically intact gabapentin exists in two forms of a stable, R, and a relatively disordered form, R*. The conversion of stable crystalline form R to the intact unstable isomer R* is considered as the primary step in the gabapentin degradation. The results exhibited that near the unstable geometry, R*, a transition state (TS), is 41.3 kcal/mol higher in energy than the optimized ground state, R* (4.1 kcal/mol). From the intrinsic reaction coordinates (IRC) computations, it can be concluded that this transition state led to the unstable R* in one direction and to gabapentin-lactam in the other. CONCLUSIONS: The thermodynamic stability of the lactam form (-13.63 kcal/mol) clarifies the more thermal stability of gaba-L than its related gabapentin form and the experimental preference for the lactamization. The corresponding energy profile on protonation/deprotonation forms of gabapentin indicates the pH-dependent of the process and the rate reduction in out of the mild pH.


Assuntos
Analgésicos/química , Compostos Aza/química , Gabapentina/química , Modelos Teóricos , Compostos de Espiro/química , Cristalização , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Isomerismo , Solventes/química , Termodinâmica , Água/química
17.
Molecules ; 24(23)2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31801249

RESUMO

The particle shape, size and distribution of active pharmaceutical ingredients (API) are relevant quality indicators of pharmaceutical tablets due to their high impact on the manufacturing process. Furthermore, the bioavailability of the APIs from the dosage form depends largely on these characteristics. Routinely, particle size and shape are only analyzed in the powder form, without regard to the effect of the formulation procedure on the particle characteristics. The monitoring of these parameters improves the understanding of the process; therefore, higher quality and better control over the biopharmaceutical profile can be ensured. A new fiber-array-based Raman hyperspectral imaging technique is presented for direct simultaneous in-situ monitoring of three different active pharmaceutical ingredients- acetylsalicylic acid, acetaminophen and caffeine- in analgesic tablets. This novel method enables a chemically selective, noninvasive assessment of the distribution of the active ingredients down to 1 µm spatial resolution. The occurrence of spherical and needle-like particles, as well as agglomerations and the respective particle size ranges, were rapidly determined for two commercially available analgesic tablet types. Subtle differences were observed in comparison between these two tablets. Higher amounts of acetaminophen were visible, more needle-shaped and bigger acetylsalicylic acid particles, and a higher incidence of bigger agglomerations were found in one of the analgesic tablets.


Assuntos
Analgésicos/análise , Analgésicos/química , Análise Espectral Raman , Acetaminofen/química , Aspirina/química , Fenômenos Químicos , Tamanho da Partícula , Análise Espectral Raman/métodos , Comprimidos
18.
Int J Mol Sci ; 20(24)2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31835716

RESUMO

Somatostatin released from the capsaicin-sensitive sensory nerves mediates analgesic and anti-inflammatory effects via the somatostatin sst4 receptor without endocrine actions. Therefore, sst4 is considered to be a novel target for drug development in pain including chronic neuropathy, which is an emerging unmet medical need. Here, we examined the in silico binding, the sst4-linked G-protein activation on stable receptor expressing cells (1 nM to 10 µM), and the effects of our novel pyrrolo-pyrimidine molecules in mouse inflammatory and neuropathic pain models. All four of the tested compounds (C1-C4) bind to the same binding site of the sst4 receptor with similar interaction energy to high-affinity reference sst4 agonists, and they all induce G-protein activation. C1 is the more efficacious (γ-GTP-binding: 218.2% ± 36.5%) and most potent (EC50: 37 nM) ligand. In vivo testing of the actions of orally administered C1 and C2 (500 µg/kg) showed that only C1 decreased the resiniferatoxin-induced acute neurogenic inflammatory thermal allodynia and mechanical hyperalgesia significantly. Meanwhile, both of them remarkably reduced partial sciatic nerve ligation-induced chronic neuropathic mechanical hyperalgesia after a single oral administration of the 500 µg/kg dose. These orally active novel sst4 agonists exert potent anti-hyperalgesic effect in a chronic neuropathy model, and therefore, they can open promising drug developmental perspectives.


Assuntos
Analgésicos/farmacologia , Analgésicos/uso terapêutico , Neuralgia/tratamento farmacológico , Receptores de Somatostatina/agonistas , Administração Oral , Analgésicos/química , Animais , Células CHO , Doença Crônica , Cricetinae , Cricetulus , Diterpenos/toxicidade , Hiperalgesia/induzido quimicamente , Hiperalgesia/complicações , Hiperalgesia/tratamento farmacológico , Inflamação/patologia , Ligantes , Masculino , Camundongos , Simulação de Dinâmica Molecular , Neuralgia/complicações , Neuralgia/patologia , Pirimidinas/química , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Pirróis/química , Pirróis/farmacologia , Pirróis/uso terapêutico , Receptores de Somatostatina/metabolismo
19.
Pak J Pharm Sci ; 32(5): 2033-2039, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31813868

RESUMO

In this present study seven novel thiazole derivatives (PM3-PM9) were synthesized by cyclization of key intermediate thiosemicarbazone (PM2), derived from 4-piperidone (PM1). The parent 4-piperidone was synthesized by Mannich condensation reaction with good yield (89%). All the derivatives were characterized by UV, IR, 1HNMR and mass spectral analysis. All the synthesized products were screened for their in vivo analgesic activities. Most of the tested compounds exhibited potential to reduce pain and some of them showed good analgesic properties. Thiosemicarbazone derivative showed most significant activity (p-value 0.01). All the thiazole derivatives exhibited dose dependent mild to good analgesic activities. Among thiazole derivatives, chloro and nitro substituted compounds (PM3, PM4, and PM5) showed highest analgesic activities.


Assuntos
Analgésicos/química , Analgésicos/farmacologia , Piperidonas/química , Piperidonas/farmacologia , Tiazóis/química , Tiazóis/farmacologia , Animais , Feminino , Masculino , Camundongos , Dor/tratamento farmacológico , Relação Estrutura-Atividade
20.
Pak J Pharm Sci ; 32(5): 2065-2073, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31813872

RESUMO

Biowaiver studies have been performed to assess the bioequivalence of two drug products. Ibuprofen is a Biopharmaceutics Classification System (BCS) class IIa drug (Low solubility - High permeability) used as analgesic, antipyretic and anti-inflammatory agent. World Health Organization (WHO) placed ibuprofen in the category of biowaiver drugs but Food and drug authority (FDA) and International Council for Harmonization (ICH) has not issued yet any guidelines regarding the biowaiver of BCS class II drugs. Present study was aimed to formulate immediate release (IR) Ibuprofen 600 mg tablets with variable disintegrants. All trial film coated formulations were evaluated physicochemically with in-vitro bioequivalence studies in three buffer mediums (pH 6.8, pH 4.5 and pH 1.2). Samples were analyzed spectrophotometrically at 221 nm and model independent approaches (dissimilarity (f1), similarity (f2;) and Boot strap) was applied to assess the observed similarity. The similarity factor (f2;) was achieved only in pH 1.2 in three trial formulations and met acceptance criteria (f2; 50-100) although the amount of drug release was negligible. This investigation revealed that for BCS class IIa drug (ibuprofen), subsequent analysis of excipients used, pKa of drug and method of manufacturing should also be considered to ensure bioequivalence for a successful biowaiver study.


Assuntos
Ibuprofeno/química , Analgésicos/química , Anti-Inflamatórios/química , Antipiréticos/química , Biofarmácia/métodos , Química Farmacêutica/métodos , Excipientes/química , Humanos , Permeabilidade/efeitos dos fármacos , Solubilidade , Comprimidos/química , Equivalência Terapêutica , Estados Unidos , United States Food and Drug Administration
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