The purpose of this study is to evaluate the effects of IV dynorphin in humans during acute heroin abstinence, in order to determine that dynorphin suppresses acute opiate withdrawal, reduces opiate craving, and is safe at doses required to produce the above effects.

开始日期1994-08-01

申办/合作机构

University of Minnesota

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100 项与 Dynorphin A 相关的临床结果

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100 项与 Dynorphin A 相关的转化医学

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100 项与 Dynorphin A 相关的专利（医药）

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1,070

项与 Dynorphin A 相关的文献（医药）

2024-07-01·NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS

A review of the kappa opioid receptor system in opioid use

Review

作者: Zhornitsky, Simon ; Funaro, Melissa C ; Matuskey, David ; Angarita, Gustavo ; Sarfo-Ansah, Wonder ; Sotomayor-Carreño, Esteban ; Cayir, Salih ; Barzegary, Alireza

The kappa opioid receptor (KOR) system is implicated in dysphoria and as an "anti-reward system" during withdrawal from opioids. However, no clear consensus has been made in the field, as mixed findings have been reported regarding the relationship between the KOR system and opioid use. This review summarizes the studies to date on the KOR system and opioids. A systematic scoping review was reported following PRISMA guidelines and conducted based on the published protocol. Comprehensive searches of several databases were done in the following databases: MEDLINE, Embase, PsycINFO, Web of Science, Scopus, and Cochrane. We included preclinical and clinical studies that tested the administration of KOR agonists/antagonists or dynorphin and/or measured dynorphin levels or KOR expression during opioid intoxication or withdrawal from opioids. One hundred studies were included in the final analysis. Preclinical administration of KOR agonists decreased drug-seeking/taking behaviors and opioid withdrawal symptoms. KOR antagonists showed mixed findings, depending on the agent and/or type of withdrawal symptom. Administration of dynorphins attenuated opioid withdrawal symptoms both in preclinical and clinical studies. In the limited number of available studies, dynorphin levels were found to increase in cerebrospinal fluid (CSF) and peripheral blood lymphocytes (PBL) of opioid use disorder subjects (OUD). In animals, dynorphin levels and/or KOR expression showed mixed findings during opioid use. The KOR/dynorphin system appears to have a multifaceted and complex nature rather than simply functioning as an anti-reward system. Future research in well-controlled study settings is necessary to better understand the clinical role of the KOR system in opioid use.

2024-01-01·Analytical and bioanalytical chemistry

Detection of dynorphin 1-17 biotransformation fragments in human nasal polyps by UPLC-QTOF-MS

Article

作者: Mohamad, Irfan ; Ballouze, Rama ; Ismail, Mohd Nazri ; Salhimi, Salizawati Muhamad ; Abu Kassim, Nur Sofiah ; Hassim, Ahmad Anuar ; Abd Mutalib, Nor Shahida ; Fazalul Rahiman, Siti Sarah

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent inflammation of the sinonasal mucosa. CRSwNP treatments are associated with inconsistent efficacy and recurrence of symptoms. Dynorphin 1-17 (DYN 1-17) and its fragments have been shown to modulate the immune response in various inflammatory conditions. This study aimed to investigate the effect of different pH and degrees of inflammation on DYN 1-17 metabolism in human CRSwNP tissues. DYN 1-17 was incubated with grade 3 and grade 4 inflamed tissues of CRSwNP patients at pH 5.5 and pH 7.4 over a range of incubation periods. The resulting fragments were identified using an ultra-performance liquid chromatography (UPLC) system coupled to quadrupole-time of flight (QTOF) mass spectrometry based on their accurate mass. The rate of DYN 1-17 fragmentation was slower at pH 5.5 in comparison to pH 7.4. The extent and rate of metabolism of DYN 1-17 were much lower in grade 3 inflamed tissue (31-32 fragments) than in grade 4 (34-41 fragments). N-Terminal fragments (DYN 1-15, 1-11, 1-10, and 1-6) were metabolized slower at pH 5.5 as compared to pH 7.4. DYN 1-12, 1-8, 2-10, 4-10, 5-10, and 8-14 were only observed under the inflammatory pH while DYN 5-17 and 6-17 were only identified upon incubation with grade 4 CRSwNP tissues. DYN 1-17 metabolism was significantly affected by the pH level and the severity of the inflammation of CRSwNP tissues, indicating the potential roles of DYN 1-17 and its fragments in modulating the inflammatory response and their avenue as therapeutics in future studies.

2023-12-01·Bioelectrochemistry (Amsterdam, Netherlands)

Probing electrophysiological activity of amphiphilic Dynorphin A in planar neutral membranes reveals both ion channel-like activity and neuropeptide translocation

Article

作者: Queralt-Martín, María ; Alvero-Gonzalez, Laidy M ; Perálvarez-Marín, Alex ; Aurora Perini, D ; Viñas, Clara ; Alcaraz, Antonio

Dynorphin A (DynA) is an endogenous neuropeptide that besides acting as a ligand of the κ-opioid receptor, presents some non-opioid pathophysiological properties associated to its ability to induce cell permeability similarly to cell-penetrating peptides (CPPs). Here, we use electrophysiology experiments to show that amphiphilic DynA generates aqueous pores in neutral membranes similar to those reported previously in charged membranes, but we also find other events thermodynamically incompatible with voltage-driven ion channel activity (i.e. non-zero currents with no applied voltage in symmetric salt conditions, reversal potentials that exceed the theoretical limit for a given salt concentration gradient). By comparison with current traces generated by other amphiphilic molecule known to spontaneously cross membranes, we hypothesize that DynA could directly translocate across neutral bilayers, a feature never observed in charged membranes following the same electrophysiological protocol. Our findings suggest that DynA interaction with the cellular membrane is modulated by the lipid charge distribution, enabling either passive ionic transport via membrane remodeling and pore formation or by peptide direct internalization independent of cellular transduction pathways.

项与 Dynorphin A 相关的新闻（医药）

2023-04-04

·BioSpace

PreveCeutical Medical Announces Frontiers Media SA Publication Featuring Data from its Analgesic Program for the Treatment of Peptide-based Therapeutics for Moderate to Severe Pain

Synthesized Kappa Opioid Receptors (KOP) Appear to be Devoid of Many Problematic Mu Receptor Side-effects Such as Tolerance, Addiction, Sedation, and Euphoria/Dysphoria, KOP Peptides Showed Significant Opioid-like Antinociception Comparable to Morphine and U50844H PreveCeutical's Pain Management Peptides Program Published in the Swiss Medical Journal. Vancouver, British Columbia--(News - April 4, 2023) - PreveCeutical Medical Inc. (CSE: PREV) (OTCQB: PRVCF) (FSE: 18H) (the "Company" or "PreveCeutical") is pleased to announce the full independent peer-reviewed publication of an article on the design and development of its non-addictive analgesic program ("Analgesic Program"). The article entitled, "Design and development of novel, short, stable dynorphin-based opioid agonists for safer analgesic therapy," was published in Frontiers Media SA (the "Frontiers") and can be found here. The article is published under the journal's open-access scheme. The Analgesic Program was initiated in July 2018 and was designed to discover and develop peptide-based therapeutics for moderate to severe pain. The program was successfully completed in March 2021, and in March 2023, PreveCeutical began preparation with a world-leading CRO to advance the Analgesic Program into Phase 1 clinical trials. The class of compounds, peripheral Kappa opioid receptor (KOPr) agonists, are considered potential analgesics without the dose-limiting central nervous system-mediated side effects. The potency and duration of action of peptides identified in the study were comparable to the clinical standard morphine, in-vivo. PreveCeutical's Chair and Chief Executive Officer, Mr. Stephen Van Deventer, stated, "Having an independent peer-reviewed article from PreveCeutical's program and having it published in the prestigious Frontiers is a big milestone for our non-addictive analgesic program. Therapies based on these potentially non-addictive peptides will be important in addressing the current opioid crisis." Frontiers is the leading international general pharmacology journal representing the 3rd most-cited and 6th largest open science research platform publisher. It publishes high-quality original research and authoritative reviews, addresses topical pharmacology issues, and is committed to transparency and scientific rigour. About PreveCeutical PreveCeutical is a health sciences company that develops innovative options for preventive and curative therapies utilizing organic and nature identical products. The Company aims to be a leader in the preventive health sciences sector. With the completion of three of its research programs, the Company is actively working on the development, clinical trials, and commercialization of its products; and has filed a number of provisional patent applications to protect the intellectual property from its research programs. The Company is currently in the research and development stage for dual gene curative and preventive therapies for diabetes and obesity. For more information about PreveCeutical, please visit our website, or follow us on Twitter and Facebook. On behalf of the Board of Directors of PreveCeutical Stephen Van Deventer, Chairman and Chief Executive Officer For further information, please contact: Stephen Van Deventer: +1 604 306 9669 Or Investor Relations ir@preveceutical.com Forward-Looking Statements: This news release contains forward-looking statements and forward-looking information (collectively, "forward-looking statements") within the meaning of applicable Canadian and U.S. securities legislation, including the United States Private Securities Litigation Reform Act of 1995. All statements in this news release that are not purely historical are forward-looking statements and include statements regarding beliefs, plans, expectations and orientations regarding the future, including, without limitation, matters related to the Company's current and planned research and development programs, including the Analgesic Program, the Company's anticipated business plans and its prospect of success in executing its proposed plans. Often, but not always, forward-looking statements can be identified by words such as "will", "plans", "expects", "may", "intends", "anticipates", "believes", "proposes", or variations of such words including negative variations thereof and phrases that refer to certain actions, events or results that may, could, would, might or will occur or be taken or achieved. Forward-looking statements are based on certain assumptions regarding the Company, including expected growth, results of operations, including the Company's research and development activities, performance, industry trends, growth opportunities, and that the Company will be able to obtain the financing required to carry out its planned future activities, retain and attract qualified research personnel and obtain and/or maintain the necessary intellectual property rights it needs to carry out its future business activities. Actual results could differ from those projected in any forward-looking statements due to numerous factors including, risks and uncertainties relating to the Analgesic Program, complexities and delays in connection with research and development activities and the actual results of research and development activities, and the inability of the Company, to, among other things, obtain any required governmental, regulatory or stock exchange approvals, permits, consents or authorizations required, including Canadian Securities Exchange acceptance of any planned future activities, commercialize therapeutic and diagnostic technologies, execute its proposed business plans, pursue business partnerships, complete its research and product development programs as planned, including the Analgesic Program, and obtain the financing required to carry out its planned future activities. Other factors such as general economic, market or business conditions or changes in laws, regulations and policies affecting the healthcare and cannabis industries in Canada may also adversely affect the future results or performance of the Company. These forward-looking statements are made as of the date of this news release and, unless required by applicable law, the Company assumes no obligation to update the forward-looking statements or to update the reasons why actual results could differ from those projected in these forward-looking statements. Although the Company believes that the statements, beliefs, plans, expectations, intentions, and assumptions contained in this news release are reasonable, there can be no assurance that those statements, beliefs, plans, expectations, intentions, or assumptions will prove to be accurate. Readers should consider all of the information set forth herein and should also refer to other periodic reports provided by the Company from time-to-time. These reports and the Company's filings are available at . Readers are cautioned that forward-looking statements are not guarantees of future performance or events and, accordingly, are cautioned not to put undue reliance on forward-looking statements due to the inherent uncertainty of such statements. To view the source version of this press release, please visit

2023-01-25

·BioSpace

PreveCeutical - Australian Patent Granted for Disulfide Bond Containing Compounds

Vancouver, British Columbia--(News - January 25, 2023) - PreveCeutical Medical Inc. (CSE: PREV) (OTCQB: PRVCF) (FSE: 18H) (the "Company" or "PreveCeutical"), is pleased to announce the grant of Australian patent no. 2018305726, titled "Disulfide bond containing compounds and uses thereof," on January 5, 2023. The patent is owned by the University of Queensland (UQ) in Australia, and UniQuest (UQ's commercialization company) has licensed it exclusively to PreveCeutical. The Australian patent protects the disulfide linker platform technology, which is used in peptides forming part of PreveCeutical's BSV (blue scorpion venom) peptide program, Non-Analgesic Dynorphin (Painkiller) and D&O (Diabetes & Obesity) Gene Therapy siRNA program. Together with the January 31, 2023, grant of the corresponding US patent (US11,566,044), obtaining a grant of this patent family forms part of PreveCeutical's overall IP strategy to secure protection for all key aspects of its technology. PreveCeutical expects further patents to be granted in other global jurisdictions. PreveCeutical's Chief Executive Officer, Mr. Stephen Van Deventer, commented, "We are very pleased with the Australian grant of this patent towards the Linker technology as this is very important to three of PreveCeutical's four therapeutic programs, specifically BSV Peptides, Dynorphin Peptides and Diabetes and Obesity Gene Therapy. This contributes towards the protection in Australia of the key technology underpinning three of our four existing programs." Although PreveCeutical believes that any such intentions, plans, estimates, beliefs, and expectations in this news release are reasonable, there can be no assurance that any such intentions, plans, beliefs, and expectations will prove to be accurate or successful. About PreveCeutical PreveCeutical is a health sciences company that develops innovative options for preventive and curative therapies utilizing organic and nature identical products. The Company aims to be a leader in the preventive health sciences sector. With the completion of three of its research programs, the Company is actively working on the development, clinical trials, and commercialization of its products; and has filed a number of provisional patent applications to protect the intellectual property from its research programs. For more information about PreveCeutical, please visit our website or follow us on Twitter and Facebook. On behalf of the Board of Directors of PreveCeutical Stephen Van Deventer, Chairman and Chief Executive Officer For further information, please contact: Stephen Van Deventer: +1 604 306 9669 Or Investor Relations ir@preveceutical.com Forward-Looking Statements: This news release contains forward-looking statements and forward-looking information (collectively, "forward-looking statements") within the meaning of applicable Canadian and U.S. securities legislation, including the United States Private Securities Litigation Reform Act of 1995. All statements in this news release that are not purely historical are forward-looking statements and include statements regarding beliefs, plans, expectations and orientations regarding the future, including, without limitation, matters related to the Company's current and planned research and development programs, including the Analgesic Program, the Company's anticipated business plans and its prospect of success in executing its proposed plans. Often, but not always, forward-looking statements can be identified by words such as "will", "plans", "expects", "may", "intends", "anticipates", "believes", "proposes" or variations of such words including negative variations thereof and phrases that refer to certain actions, events or results that may, could, would, might or will occur or be taken or achieved. Forward-looking statements are based on certain assumptions regarding the Company, including expected growth, results of operations, including the Company's research and development activities, performance, industry trends, growth opportunities, and that the Company will be able to obtain the financing required to carry out its planned future activities, retain and attract qualified research personnel and obtain and/or maintain the necessary intellectual property rights it needs to carry out its future business activities. Actual results could differ from those projected in any forward-looking statements due to numerous factors including, risks and uncertainties relating to the Analgesic Program, complexities and delays in connection with research and development activities and the actual results of research and development activities, and the inability of the Company, to, among other things, obtain any required governmental, regulatory or stock exchange approvals, permits, consents or authorizations required, including Canadian Securities Exchange acceptance of any planned future activities, commercialize therapeutic and diagnostic technologies, execute its proposed business plans, pursue business partnerships, complete its research and product development programs as planned, including the Analgesic Program, and obtain the financing required to carry out its planned future activities. Other factors such as general economic, market or business conditions or changes in laws, regulations and policies affecting the healthcare and cannabis industries in Canada may also adversely affect the future results or performance of the Company. These forward-looking statements are made as of the date of this news release and, unless required by applicable law, the Company assumes no obligation to update the forward-looking statements or to update the reasons why actual results could differ from those projected in these forward-looking statements. Although the Company believes that the statements, beliefs, plans, expectations, intentions, and assumptions contained in this news release are reasonable, there can be no assurance that those statements, beliefs, plans, expectations, intentions or assumptions will prove to be accurate. Readers should consider all of the information set forth herein and should also refer to other periodic reports provided by the Company from time-to-time. These reports and the Company's filings are available at . Readers are cautioned that forward-looking statements are not guarantees of future performance or events and, accordingly, are cautioned not to put undue reliance on forward-looking statements due to the inherent uncertainty of such statements. To view the source version of this press release, please visit

基因疗法

100 项与 Dynorphin A 相关的药物交易

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