We have located links that may give you full text access.
JOURNAL ARTICLE
REVIEW
Indirect-acting strategy of opioid action instead of direct receptor activation: dual-acting enkephalinase inhibitors (DENKIs).
Journal of Clinical Pharmacy and Therapeutics 2018 August
WHAT IS KNOWN AND OBJECTIVE: Although pain is one of the most common afflictions, it is often inadequately managed because the available analgesic options are relatively limited due to insufficient efficacy, unacceptable adverse effects or the potential for misuse or abuse. However, recent publications suggest that an alternative approach-indirect enhancement of endogenous pain-relieving pathways-might be desirable. We review this approach, in particular the dual enkephalinase inhibitors (DENKIs).
METHODS: Published literature and Internet sources were searched for information related to the basic science and clinical data on inhibition of metabolic pathways of endogenous analgesic agents. The identified sources were reviewed, assessed and synthesized. Emphasis was placed on the benefits of the approach, as well as on the individual agents.
RESULTS: Inhibition of the enzymes that degrade the endogenous opioid ligands Met- and Leu-enkephalin results in an increased synaptic concentration of the enkephalins and an analgesic effect in a variety of animal models of pain and in preliminary trials in humans. The design of compounds that inhibit both of the two major enkephalin-degrading enzymes (neprilysin and aminopeptidase N) has been found to be better than those that inhibit only one of the enzymes. These dual-acting enkephalinase inhibitors yield analgesia with less adverse effects than current opioid drugs.
WHAT IS NEW AND CONCLUSION: Unlike currently available analgesics, inhibitors of the metabolic degradation of endogenous analgesic substances attempt to elicit a more "natural" and targeted analgesic effect. This indirect approach offers an opportunity for novel additions to the otherwise relatively limited choice of analgesic classes.
METHODS: Published literature and Internet sources were searched for information related to the basic science and clinical data on inhibition of metabolic pathways of endogenous analgesic agents. The identified sources were reviewed, assessed and synthesized. Emphasis was placed on the benefits of the approach, as well as on the individual agents.
RESULTS: Inhibition of the enzymes that degrade the endogenous opioid ligands Met- and Leu-enkephalin results in an increased synaptic concentration of the enkephalins and an analgesic effect in a variety of animal models of pain and in preliminary trials in humans. The design of compounds that inhibit both of the two major enkephalin-degrading enzymes (neprilysin and aminopeptidase N) has been found to be better than those that inhibit only one of the enzymes. These dual-acting enkephalinase inhibitors yield analgesia with less adverse effects than current opioid drugs.
WHAT IS NEW AND CONCLUSION: Unlike currently available analgesics, inhibitors of the metabolic degradation of endogenous analgesic substances attempt to elicit a more "natural" and targeted analgesic effect. This indirect approach offers an opportunity for novel additions to the otherwise relatively limited choice of analgesic classes.
Full text links
Related Resources
Trending Papers
Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.Clinical Research in Cardiology : Official Journal of the German Cardiac Society 2024 April 12
Proximal versus distal diuretics in congestive heart failure.Nephrology, Dialysis, Transplantation 2024 Februrary 30
World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management.American Journal of Hematology 2024 March 30
Efficacy and safety of pharmacotherapy in chronic insomnia: A review of clinical guidelines and case reports.Mental Health Clinician 2023 October
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app