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Molecules (Basel, Switzerland) Nov 2020Thiazinanes and its isomeric forms represent one of the most important heterocyclic compounds, and their derivatives represented a highly potent drug in disease... (Review)
Review
Thiazinanes and its isomeric forms represent one of the most important heterocyclic compounds, and their derivatives represented a highly potent drug in disease treatment such as, 1,1-dioxido-1,2-thiazinan-1,6-naphthyridine, which has been shown to have anti-HIV activity by a mechanism that should work as anti-AIDS treatment, while ()-methyl 3-(naphthalen-1-ylimino)- 2-thia-4-azaspiro[5 5]undecane-4-carbodithioate showed analgesic activity, cephradine was used as antibiotic and chlormezanone was utilized as anticoagulants. All publications were interested in the chemistry of thiazine (partially or fully unsaturated heterocyclic six-membered ring containing nitrogen and sulfur), but no one was dealing with thiazinane itself which encouraged us to shed new light on these interesting heterocycles. This review was focused on the synthetic approaches of thiazinane derivatives and their chemical reactivity.
Topics: Analgesics; Animals; Anti-Bacterial Agents; Anticoagulants; Heterocyclic Compounds; Humans; Thiazines
PubMed: 33260625
DOI: 10.3390/molecules25235610 -
Frontiers in Public Health 2022There is a dearth of research on the incidence and treatment of cancer pain in Africa. Yet Africa, with other developing countries, accounts for more than half of all... (Review)
Review
Cancer Pain Management in French-Speaking African Countries: Assessment of the Current Situation and Research Into Factors Limiting Treatment and Access to Analgesic Drugs.
INTRODUCTION
There is a dearth of research on the incidence and treatment of cancer pain in Africa. Yet Africa, with other developing countries, accounts for more than half of all cancer diagnoses, and it is estimated that cancer incidence in Africa will double by 2030.
OBJECTIVES
This research protocol outlines an approach to investigate cancer pain in French-speaking African countries. The protocol intends to determine and describe the treatment and management of cancer pain in these countries. Barriers to treating cancer pain will be explored and the results will be collated to make a series of recommendations on policy positions, regulatory frameworks and protocols.
METHODS
A mixed-methods, co-creation methodology has been selected to ensure the societal impact of the research outcomes. This research will use both qualitative and quantitative data collection methods and analyses. The research will begin with a review of the policies and legislation that exist in relation to cancer pain management and the use of analgesics, in each French-speaking African country. An Experts Steering Committee will then be created to provide guidance on the protocol and research design and access to participants, as well as to execute on the administration of surveys to local structures and international experts. A series of semi-structured, qualitative interviews with experts and clinicians in the field of screening and management of cancer pain and access to treatment will follow. Purposive and snowball sampling will be used to select the respondent experts. The semi-structured interviews will be conducted to determine the main trends and barriers to the treatment of cancer pain in French-speaking African countries. From this qualitative research, two surveys will be developed and then administered: one to validate the policy and regulatory context, and the other to determine experts and healthcare professionals experience and perceptions of cancer pain.
RESULTS/CONCLUSIONS
The results will be analyzed using quantitative and qualitative methods to determine themes and perceptions of cancer pain and treatment, from the policy level to the healthcare professional level. Evaluation of the results will lead to recommendations for a comprehensive framework for cancer pain treatment in French-speaking Africa.
Topics: Africa; Analgesics; Health Personnel; Humans; Neoplasms; Pain Management
PubMed: 35372204
DOI: 10.3389/fpubh.2022.846042 -
Alternative Therapies in Health and... Apr 2024The objective of this study was to investigate the preventive and therapeutic effects of Shenzhu Jiedu Granule on COVID-19 using network pharmacology and animal...
OBJECTIVE
The objective of this study was to investigate the preventive and therapeutic effects of Shenzhu Jiedu Granule on COVID-19 using network pharmacology and animal experiments.
METHODS
Obtain the chemical components of Shenshu Jiedu Granule from the online pharmacology database and analysis platform (ETCM) of the Chinese traditional medicine system, obtain the potential target of the compound through the UniProt database, and obtain the related target of COVID-19 from GeneCards and OMIM databases; Construct a component target network diagram using Cytascape 3.7.0 software, import the protein interaction (PPI) of intersection targets into Cytascape software through STRING database, and use the Metascape platform to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) enrichment analysis on intersection targets.To explore its anti-inflammatory and analgesic effects through animal ear swelling, hot plate and torsion experiments.
RESULTS
Analysis revealed 72 key target proteins associated with the effects of Shenzhu Jiedu Granule demonstrated that mainly interleukin-6 (IL-6), interleukin-1 β (IL 1 β), B cells κ Light peptide gene enhancer nuclear factor inhibitor 1 (NFKB1), B cells κ Light peptide gene enhancer nuclear factor inhibitor 1B (NFKB1A), interferon β IFNB1, tumor necrosis factor TNF, recombinant human mitogen activated protein kinase 12 (MAPK12), serine/threonine kinase 1 (AKT1), B cells κ Light peptide gene enhancer inhibitor kinase β (IKBKB), etc.The analysis found that it is mainly related to multiple biological processes such as intercellular immune regulation, inflammatory cytokines, and ion channels in the microenvironment; KEGG analysis showed that COVID-19 pathway, influenza virus pathway and multiple immune inflammatory response pathways were mainly involved. Obtained 91 effective ingredients of Shenshu Jiedu Granule, 10 anti-inflammatory, bactericidal, and antiviral compounds, and 4 immune enhancing compounds. Shenzhu Jiedu Granule demonstrated an inhibitory effect on xylene-induced ear swelling in mice and significantly enhanced the anti-inflammatory and analgesic effects by reducing body twists and prolonging the time mice licked their feet.
CONCLUSIONS
It is suggested that Shenzhu Jiedu Granule has anti COVID-19, influenza virus, antibacterial and anti-inflammatory effects, and can significantly enhance the anti-inflammatory and analgesic effects of mice, which highlight the significance of the study in the context of current global health concerns.
Topics: Animals; Drugs, Chinese Herbal; Network Pharmacology; Mice; Anti-Inflammatory Agents; Analgesics; COVID-19 Drug Treatment; SARS-CoV-2; COVID-19; Male; Humans; Disease Models, Animal
PubMed: 37883768
DOI: No ID Found -
Journal of Pain and Symptom Management Nov 1994There has been long-standing debate regarding whether benzodiazepines possess analgesic properties that are independent of their effects on mood and alertness. A careful... (Review)
Review
There has been long-standing debate regarding whether benzodiazepines possess analgesic properties that are independent of their effects on mood and alertness. A careful review of the literature reveals insufficient evidence to support the contention that the benzodiazepines have meaningful analgesic properties in most clinical circumstances. Treatment with the benzodiazepines may reduce complaints of pain, but this seems to be an indirect effect related to their psychotropic properties, such as alleviation of anxiety and, in selected cases, depression. In the absence of definitive data, clinical experience suggests a potential role for treatment with benzodiazepines for acute muscle spasm, concomitant chronic pain and anxiety, and lancinating neropathic pain, in which case clonazepam and alprazolam may be the agents of choice. They should probably not be considered as first-line choices even for the above indications, since potential benefits must be considered in the context of potential for the development of cognitive impairment, physical and psychological dependence, worsening depression, overdose, and other side effects.
Topics: Adjuvants, Pharmaceutic; Analgesics; Benzodiazepines; Clinical Trials as Topic; Humans; Palliative Care
PubMed: 7531735
DOI: 10.1016/0885-3924(94)90112-0 -
Science Translational Medicine Nov 2021Despite substantial efforts dedicated to the development of new, nonaddictive analgesics, success in treating pain has been limited. Clinically available analgesic...
Despite substantial efforts dedicated to the development of new, nonaddictive analgesics, success in treating pain has been limited. Clinically available analgesic agents generally lack efficacy and may have undesirable side effects. Traditional target-based drug discovery efforts that generate compounds with selectivity for single targets have a high rate of attrition because of their poor clinical efficacy. Here, we examine the challenges associated with the current analgesic drug discovery model and review evidence in favor of stem cell–derived neuronal-based screening approaches for the identification of analgesic targets and compounds for treating diverse forms of acute and chronic pain.
Topics: Analgesics; Chronic Pain; Humans; Nociceptors
PubMed: 34757806
DOI: 10.1126/scitranslmed.abj9837 -
Annals of Medicine Apr 1995The concept and value of 'multimodal' or 'balanced' analgesia in the treatment of postoperative pain is reviewed. Based upon the relatively few multimodal studies... (Review)
Review
The concept and value of 'multimodal' or 'balanced' analgesia in the treatment of postoperative pain is reviewed. Based upon the relatively few multimodal studies compared to unimodal studies, it is concluded that a combination of analgesics will improve pain relief including movement-associated pain. Since analgesic combination therapy is rational, further studies are needed to evaluate the optimal combination for each surgical procedure, as well as to assess the risk of side effects and need for surveillance in large-scale studies.
Topics: Analgesia; Analgesics; Drug Synergism; Drug Therapy, Combination; Humans; Pain, Postoperative
PubMed: 7632423
DOI: 10.3109/07853899509031968 -
Journal of Medicinal Chemistry Oct 2019Voltage-gated sodium ion channel subtype 1.7 (Na1.7) is a high interest target for the discovery of non-opioid analgesics. Compelling evidence from human genetic data,... (Review)
Review
Voltage-gated sodium ion channel subtype 1.7 (Na1.7) is a high interest target for the discovery of non-opioid analgesics. Compelling evidence from human genetic data, particularly the finding that persons lacking functional Na1.7 are insensitive to pain, has spurred considerable effort to develop selective inhibitors of this Na ion channel target as analgesic medicines. Recent clinical setbacks and disappointing performance of preclinical compounds in animal pain models, however, have led to skepticism around the potential of selective Na1.7 inhibitors as human therapeutics. In this Perspective, we discuss the attributes and limitations of recently disclosed investigational drugs targeting Na1.7 and review evidence that, by better understanding the requirements for selectivity and target engagement, the opportunity to deliver effective analgesic medicines targeting Na1.7 endures.
Topics: Analgesics; Animals; Disease Models, Animal; Humans; NAV1.7 Voltage-Gated Sodium Channel; Pain; Protein Isoforms; Signal Transduction; Sodium Channel Blockers; Sulfonamides
PubMed: 31012583
DOI: 10.1021/acs.jmedchem.8b01906 -
BMC Anesthesiology Aug 2022Humane treatment requires the provision of appropriate sedation and analgesia during medical diagnosis and treatment. However, limited information is available about the...
BACKGROUND
Humane treatment requires the provision of appropriate sedation and analgesia during medical diagnosis and treatment. However, limited information is available about the status of procedural analgesic interventions in Chinese hospitals. Therefore, a nationwide survey was established to identify challenges and propose potential improvement strategies.
METHODS
Forty-three members of the Pain Group of Chinese Society of Anesthesiology established and reviewed the questionnaire, which included (1) general information on the hospitals, (2) the sedation/analgesia rate in gastrointestinal endoscopy, labor, flexible bronchoscopy, hysteroscopy in China, (3) staff assignments, (4) drug use for procedural analgesic interventions, and (5) difficulties in procedural analgesic interventions. The data were obtained using an online questionnaire sent to the chief anesthesiologists of Chinese hospitals above Grade II or members of the Pain Group of Chinese Society of Anesthesiology.
RESULTS
Valid and complete questionnaires were received from 2198 (44.0%) hospitals, of which 64.5% were Grade III. The overall sedation/analgesia rates were as follows: gastroscopy (50.6%), colonoscopy (53.7%), ERCP (65.9%), induced abortion (67.5%), labor (42.3%), hysteroscopy (67.0%) and fiber bronchoscopy (52.6%). Compared with Grade II hospitals, Grade III hospitals had a higher proportion of procedural analgesic interventions services except for induced abortion. On average (median [IQR]), each anesthesiologist performed 5.7 [2.3-11.4] cases per day, with 7.3 [3.2-13.6] performed in Grade III hospitals and 3.4 [1.8-6.8] performed in Grade II hospitals (z = -7.065, p < 0.001).
CONCLUSIONS
Chinese anesthesiologists have made great efforts to achieve procedural analgesic interventions, as evidenced by the increased rate. The uneven health care provided by hospitals at different levels and in different regions and the lack of anesthesiologists are the main barriers to optimal procedural analgesic interventions.
Topics: Analgesia; Analgesics; Anesthesiology; Female; Hospitals; Humans; Pain; Pregnancy
PubMed: 35933333
DOI: 10.1186/s12871-022-01783-6 -
International Journal of Molecular... Dec 2022The mechanism of acetaminophen (APAP) analgesia is at least partially unknown. Previously, we showed that the APAP metabolite N-acetyl-p-benzoquinone imine (NAPQI)...
The mechanism of acetaminophen (APAP) analgesia is at least partially unknown. Previously, we showed that the APAP metabolite N-acetyl-p-benzoquinone imine (NAPQI) activated Kv7 channels in neurons in vitro, and this activation of Kv7 channels dampened neuronal firing. Here, the effect of the Kv7 channel blocker XE991 on APAP-induced analgesia was investigated in vivo. APAP had no effect on naive animals. Induction of inflammation with λ-carrageenan lowered mechanical and thermal thresholds. Systemic treatment with APAP reduced mechanical hyperalgesia, and co-application of XE991 reduced APAP's analgesic effect on mechanical pain. In a second experiment, the analgesic effect of systemic APAP was not antagonized by intrathecal XE991 application. Analysis of liver samples revealed APAP and glutathione-coupled APAP indicative of metabolization. However, there were no relevant levels of these metabolites in cerebrospinal fluid, suggesting no relevant APAP metabolite formation in the CNS. In summary, the results support an analgesic action of APAP by activating Kv7 channels at a peripheral site through formation of the metabolite NAPQI.
Topics: Animals; Acetaminophen; Analgesics, Non-Narcotic; Imines; Analgesics; Liver
PubMed: 36614094
DOI: 10.3390/ijms24010650 -
Toxins Sep 2015The α9α10-nicotinic acetylcholine receptor (nAChR) has been implicated in pain and has been proposed to be a novel target for analgesics. However, the evidence to... (Review)
Review
The α9α10-nicotinic acetylcholine receptor (nAChR) has been implicated in pain and has been proposed to be a novel target for analgesics. However, the evidence to support the involvement of the α9α10-nAChR in pain is conflicted. This receptor was first implicated in pain with the characterisation of conotoxin Vc1.1, which is highly selective for α9α10-nAChRs and is an efficacious analgesic in chronic pain models with restorative capacities and no reported side effects. Numerous other analgesic conotoxin and non-conotoxin molecules have been subsequently characterised that also inhibit α9α10-nAChRs. However, there is evidence that α9α10-nAChR inhibition is neither necessary nor sufficient for analgesia. α9α10-nAChR-inhibiting analogues of Vc1.1 have no analgesic effects. Genetically-modified α9-nAChR knockout mice have a phenotype that is markedly different from the analgesic profile of Vc1.1 and similar conotoxins, suggesting that the conotoxin effects are largely independent of α9α10-nAChRs. Furthermore, an alternative mechanism of analgesia by Vc1.1 and other similar conotoxins involving non-canonical coupling of GABAB receptors to voltage-gated calcium channels is known. Additional incongruities regarding α9α10-nAChRs in analgesia are discussed. A more comprehensive characterisation of the role of α9α10-nAChRs in pain is crucial for understanding the analgesic action of conotoxins and for improved drug design.
Topics: Analgesics; Animals; Conotoxins; Disease Models, Animal; Humans; Mice, Knockout; Nicotinic Antagonists; Pain; Rats; Receptors, Nicotinic
PubMed: 26426047
DOI: 10.3390/toxins7103916