-
Scientific Reports Apr 202110-Alkylthiocolchicines have been obtained and characterized by spectroscopic methods and their biological activities as: cytotoxic, anti-inflammatory and analgesic...
10-Alkylthiocolchicines have been obtained and characterized by spectroscopic methods and their biological activities as: cytotoxic, anti-inflammatory and analgesic activities have been tested. Cytotoxic activity against SKOV-3 ovarian cell line for 10-alkylthiocolchicine analogues was reported and tested compounds showed to be more active than commonly used doxorubicin. Some of tested C-10 alkylthiolated colchicines have been found to exhibit cytotoxicity at levels comparable to that of the natural product-colchicine. 10-Methylthiocolchicine has IC = 8 nM and 10-ethylthiocolchicine has IC = 47 nM in comparison to colchicine IC = 37 nM. Moreover for 10-alkylthioderivatives apoptosis test, cyclin B1 and cell cycle tests were performed. 10-n-Butylthiocolchicine was tested for anti-inflammatory and analgesic activities it showed to produce analgesic rather than anti-inflammatory effect.
Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Colchicine; Drug Screening Assays, Antitumor; Humans; Male; Rats; Rats, Wistar; Sulfur Compounds
PubMed: 33907227
DOI: 10.1038/s41598-021-88260-1 -
Mini Reviews in Medicinal Chemistry 20181,2,4-Oxadiazole is one of the important heterocycles used by medicinal chemists in designing a new therapeutic molecule. The compounds containing this nucleus are... (Review)
Review
1,2,4-Oxadiazole is one of the important heterocycles used by medicinal chemists in designing a new therapeutic molecule. The compounds containing this nucleus are reported to have a wide range of pharmaceutical and biological applications including anti-inflammatory and analgesic activities. The fused and pendent 1,2,4-oxadiazole moiety has been traced in a number of well established, commercially available drugs. This review article provides an up to date information about techniques adopted for the synthesis of 1,2,4-oxadiazoles, and their therapeutic importance as anti-inflammatory and analgesic agents.
Topics: Analgesics; Animals; Anti-Inflammatory Agents; Humans; Neutrophils; Oxadiazoles
PubMed: 29792145
DOI: 10.2174/1389557518666180524112050 -
Current Opinion in Anaesthesiology Oct 2015This article summarizes recent data related to the safety and efficacy of postoperative analgesia in children that influence clinical practice recommendations. (Review)
Review
PURPOSE OF REVIEW
This article summarizes recent data related to the safety and efficacy of postoperative analgesia in children that influence clinical practice recommendations.
RECENT FINDINGS
Postoperative pain continues to be experienced by hospitalized children and following discharge after short stay or ambulatory surgery. Updated recommendations for post-tonsillectomy analgesia exclude codeine and suggest regular administration of paracetamol and NSAID, but evidence for the most appropriate dose and type of opioid for rescue analgesia is limited. The incidence of opioid-related respiratory depression/oversedation in hospitalized children ranges from 0.11 to 0.41%, with recent large series identifying high-risk groups and contributory factors that can be targeted to minimize the risk of serious or permanent harm. Data demonstrating feasibility and safety of regional analgesic techniques is increasing, but additional and procedure-specific evidence would improve technique selection and inform discussions of efficacy and safety with patients and families/carers. Persistent postsurgical pain is increasingly recognized following major surgery in adolescents. Evaluation of potential predictive factors in clinical studies and investigation of underlying mechanisms in laboratory studies can identify targets for both pharmacological and nonpharmacological interventions.
SUMMARY
Recommendations for postoperative pain in children continue to evolve, with data incorporated from randomized controlled trials, case series and large audits. Management of pain following surgery in children needs to not only encompass efficacy and safety in the immediate perioperative period, but also consider pain following discharge after ambulatory surgery and the potential risk of persistent postsurgical pain following major surgery.
Topics: Analgesics; Analgesics, Opioid; Child; Chronic Pain; Humans; Pain Management; Pain, Postoperative
PubMed: 26280822
DOI: 10.1097/ACO.0000000000000227 -
Comparative Medicine Dec 2019Mice and rats are valuable and commonly used as models for the study of cancer. The models and methods of experimentation have the potential to cause pain to some... (Review)
Review
Mice and rats are valuable and commonly used as models for the study of cancer. The models and methods of experimentation have the potential to cause pain to some degree, and all charged with ensuring animal welfare must determine how to manage it. A commonly posed question, especially from investigators and IACUC, is whether the provision of analgesic agents will render the model invalid. Left untreated, pain is a stressor and has negative consequences, most notably immune system perturbations. In addition, analgesic agents in the opioid and NSAID drug classes exhibit immunomodulatory activity and influence processes such as cell proliferation, apoptosis, and angiogenesis that are important in cancer formation. Therefore, both pain and the agents used to alleviate it have the potential to act as confounding factors in a study. This review article presents data from both human medicine and work with animal models in an attempt to help inform discussions about the withholding of analgesic agents from animals used in cancer studies.
Topics: Analgesics; Animals; Disease Models, Animal; Humans; Mice; Neoplasms; Pain Management; Rats; Research Design
PubMed: 31315692
DOI: 10.30802/AALAS-CM-19-000002 -
Journal of Clinical Pharmacy and... Feb 2017Chronic pain presents a difficult clinical challenge because of the limited efficacy, the limiting adverse-effect profile or the abuse potential of current analgesic... (Review)
Review
WHAT IS KNOWN AND OBJECTIVE
Chronic pain presents a difficult clinical challenge because of the limited efficacy, the limiting adverse-effect profile or the abuse potential of current analgesic options. Cebranopadol is a novel new agent in clinical trials that combines dual agonist action at opioid and nociceptin/orphanin FQ peptide (NOP) receptors. It is the first truly unique, centrally acting analgesic in several years. We here review the basic and clinical pharmacology of cebranopadol.
METHODS
Published literature and Internet sources were searched to identify information related to the basic science (pharmacology and medicinal chemistry) and development (clinical trial) information on the mechanism of dual opioid and NOP receptor pharmacologic action in general, and for cebranopadol in particular. The identified sources were reviewed and the information synthesized.
RESULTS
The preclinical testing of cebranopadol has characterized it as a dual opioid and NOP receptor agonist that displays antinociceptive and antihyperalgesic action in a variety of acute and chronic pain models in animals. Unlike most current traditional opioids, it is generally more potent against neuropathic than nociceptive pain. Several phase 2 clinical trials have been completed.
WHAT IS NEW AND CONCLUSION
Despite the medical need, a truly novel centrally acting analgesic has not been developed in many years. Cebranopadol represents a truly novel mechanistic approach. Its actual place in pain pharmacotherapy awaits the results of phase 3 clinical trials.
Topics: Analgesics; Animals; Chronic Pain; Humans; Indoles; Receptors, Opioid; Spiro Compounds; Nociceptin Receptor
PubMed: 27778406
DOI: 10.1111/jcpt.12461 -
Expert Opinion on Drug Metabolism &... 2015Assessment of analgesic drugs includes comparative studies to other analgesics and local anesthesia blockade, number needed to treat estimates and opioid sparing... (Review)
Review
INTRODUCTION
Assessment of analgesic drugs includes comparative studies to other analgesics and local anesthesia blockade, number needed to treat estimates and opioid sparing descriptions. An additional methodology is to define the concentration-response relationship using pharmacokinetic/pharmacodynamic (PK/PD) modeling.
AREAS COVERED
A concentration-response relationship allows analgesic effect comparison between drugs for different acute pain types. Covariates such as size, age and organ function impact greatly on PK in children. The cumulative effect of confounding factors (e.g., pharmacogenetics, placebo and changes in baseline pain over time) complicates PD. Other factors (outcome measures, method of measurement, failure to account for study attrition) impact on outcome. Population PK/PD modeling approaches allow us to account for these various factors to some extent.
EXPERT OPINION
Nonlinear mixed effects models help interpret analgesic data and their use is increasing. The PK is relatively well understood. The next investigative step will involve investigation into covariate effects for PD. Mathematical functions for both placebo models and dropout models are well described and should be incorporated into analgesic effectiveness studies that investigate a range of doses. Improvements in pain assessment tools and a greater understanding of pharmacogenomics factors will help individualize analgesic therapy.
Topics: Analgesics; Child; Dose-Response Relationship, Drug; Humans; Models, Biological; Nonlinear Dynamics; Pain; Pain Measurement; Pharmacogenetics
PubMed: 26155821
DOI: 10.1517/17425255.2015.1061505 -
Protein and Peptide Letters 2023As a peptide originally discovered from by mass spectrometry and cDNA sequencing, Ac6.4 contains 25 amino acid residues and three disulfide bridges. Our previous study...
BACKGROUND
As a peptide originally discovered from by mass spectrometry and cDNA sequencing, Ac6.4 contains 25 amino acid residues and three disulfide bridges. Our previous study found that this peptide possesses 80% similarity to MVIIA by BLAST and that MVIIA is a potent and selective blocker of N-type voltage-sensitive calcium channels in neurons.
OBJECTIVE
To recognize the target protein and analgesic activity of Ac6.4 from .
METHODS
In the present study, we synthesized Ac6.4, expressed the Trx-Ac6.4 fusion protein, tested Ac6.4 for its inhibitory activity against Cav2.2 in CHO cells and investigated Ac6.4 and Trx-Ac6.4 for their analgesic activities in mice.
RESULTS
Data revealed that Ac6.4 had strong inhibitory activity against Cav2.2 (IC = 43.6 nM). After intracranial administration of Ac6.4 (5, 10, 20 μg/kg) and Trx-Ac6.4 (20, 40, 80 μg/kg), significant analgesia was observed. The analgesic effects (elevated pain thresholds) were dose-dependent.
CONCLUSION
This study expands our knowledge of the peptide Ac6.4 and provides new possibilities for developing Cav2.2 inhibitors and analgesic drugs.
Topics: Mice; Animals; Cricetinae; Conus Snail; Cricetulus; Analgesics; Peptides; Calcium Channels, N-Type
PubMed: 37016524
DOI: 10.2174/0929866530666230403095018 -
Acta Pharmacologica Sinica Jul 2022Dezocine, a synthetic opioid, introduced in 1970s as an analgesic, was redeveloped for relieving moderate to severe pain by Yangtze River Pharmaceutical Group in China... (Review)
Review
Dezocine, a synthetic opioid, introduced in 1970s as an analgesic, was redeveloped for relieving moderate to severe pain by Yangtze River Pharmaceutical Group in China in 2009. To date, dezocine occupies 45% of China's opioid analgesic market. Along with dezocine being a dominated painkiller, a certain amount of research was conducted to elucidate dezocine's action. In this review we summarize the current knowledge on the receptor, preclinical and clinical pharmacology of dezocine. Briefly, preclinical data show that dezocine is effective under varying pain conditions, particularly chronic neuropathic pain and cancer pain, through activation of opioid receptors, and inhibition of norepinephrine reuptake. Clinical data establish the effectiveness of dezocine either as a primary analgesic for postoperative pain management or a supplement for balanced analgesia. The receptor profile of dezocine is different from known pure μ agonists, and allows it to be used in combination with other opioids for additivity in efficacy or lower incidence of adverse effects.
Topics: Analgesics; Analgesics, Opioid; Bridged Bicyclo Compounds, Heterocyclic; Humans; Pain; Tetrahydronaphthalenes
PubMed: 34737418
DOI: 10.1038/s41401-021-00790-6 -
Current Opinion in Supportive and... Jun 2019There is a clear unmet need for either the development of new drugs for the treatment of painful pathologies or the better use of the existing agents denoted by the lack... (Review)
Review
PURPOSE OF REVIEW
There is a clear unmet need for either the development of new drugs for the treatment of painful pathologies or the better use of the existing agents denoted by the lack of efficacy of many existing drugs in a number of patients, limitations of their use due to severity of side effects, and by the high number of drugs that fail to reach clinical efficacy from preclinical development. This account considers the efforts being made to better validate new analgesic components and to improve translational efficacy of existing drugs.
RECENT FINDINGS
A better use of the available models and tools can improve the predictive validity of new analgesic drugs, as well as using intermediate steps when translating drugs to clinical context such as characterizing drugs using stem cell-sensory derived neurones. Profiling patient sensory phenotypes can decrease the number of failed clinical trials and improve patient outcome.
SUMMARY
An integrative approach, comprising the use of complementary techniques to fully characterize drug profiles, is necessary to improve translational success of new analgesics.
Topics: Analgesics; Animals; Clinical Trials as Topic; Disease Models, Animal; Drug Development; Drug Evaluation, Preclinical; Humans; Pain; Perceptual Disorders
PubMed: 30883401
DOI: 10.1097/SPC.0000000000000425 -
Inflammopharmacology Apr 2022Caralluma tuberculata N.E. Brown (Common name: Chongan), belonging to the family Asclepiadaceae is distributed widely in hilly areas of Dir, Swat, Kohat and in plain...
Caralluma tuberculata N.E. Brown (Common name: Chongan), belonging to the family Asclepiadaceae is distributed widely in hilly areas of Dir, Swat, Kohat and in plain lands of Punjab, Pakistan. The plant has been used as a source of vegetable as well as home remedy for headache, muscle spasms and rheumatism. The present study was proposed to investigate the analgesic, anti-inflammatory and anti-arthritic potential of the aqueous methanolic extract of C. tuberculata (ICE). The dried shoots of plant were used to prepare aqueous methanolic extract (30:70) by 3 days thrice maceration and filtration followed by evaporation under reduced pressure. ICE was screened for the presence of phytochemicals using preliminary phytochemical analysis and HPLC. The antioxidant potential was evaluated through DPPH assay. Analgesic potential of ICE was studied using hot plate and tail immersion methods, and anti-inflammatory activity was performed using turpentine oil and carrageenan-induced inflammation models, in wistar albino rats. Formaldehyde-induced and Complete Freund's Adjuvant-induced arthritis models were used for the assessment of anti-arthritic activity of ICE and its effects on serum levels of PGE-2 as well as gene expression levels of pro-inflammatory cytokines were studied. ICE displayed a dose-dependent (300-1000 mg/Kg p.o.) analgesic effect in hot plate (maximum retention time of 10.87 and 13 s) and tail immersion (response time of 11 and 13.64 s) tests at the doses of 500 and 1000 mg/Kg, respectively. The extract exhibited a significant decrease in paw inflammation of rats at the doses of 500 and 1000 mg/Kg as compared to the disease control group. ICE also exhibited a remarkable decline in arthritic score and a dose-dependent drop in serum levels of prostaglandin E2. There was a significant suppression in the expression of TNF-α, IL-1β, IL-6, NF-κB and cyclooxygenase enzyme in treatment groups. This study concludes that Caralluma tuberculata exhibits strong analgesic, anti-inflammatory, antioxidant and anti-arthritic activities thus upholding the vernacular use of the plant for pain and rheumatism.
Topics: Analgesics; Animals; Apocynaceae; Arthritis, Experimental; Cytokines; Edema; Oxidative Stress; Plant Extracts; Rats
PubMed: 35257282
DOI: 10.1007/s10787-022-00949-5