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Novel Chemical and Biological Agents in the Treatment of Pain...
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Novel Chemical and Biological Agents in the Treatment of Pain and Substance Use Disorders

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 July 2024) | Viewed by 3948

Special Issue Editors

Dr. Samuel Obeng

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA
Interests: pain; addiction; opioids; GPCRs; synthesis; self-administration; drug discrimination
Prof. Dr. Christopher R. McCurdy

E-Mail Website
Guest Editor
Department Medicinal Chemistry, Translational Drug Development Core, Clinical and Translational Sciences Institute, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA
Interests: drug abuse and addiction; pain anxiety; medicinal chemistry; natural products; drug development

Special Issue Information

Dear Colleagues,

In the United States, drug overdose is one of the leading causes of death in adults aged 50 and under. In 2017, over 750,000 drug overdose deaths worldwide were attributed to drug abuse or substance use disorder. More than 70% of these deaths were due to opioids. Effective treatments for substance use disorder will help reduce these preventable deaths. In addition to the health impact of substance abuse on the individuals and their families, illicit drug use has a huge economic burden, estimated to cost about USD 193 billion in the United States alone. Thus, there is the need for novel molecules as treatments for substance use disorder. Moreover, there is a need for novel treatments for pain that do not have abuse liabilities. This Special Issue is dedicated to highlighting recent advancements in substance abuse and pain research. The scope includes, but is not limited to, the discovery and development of novel compounds to treat pain and substance use disorders, new therapeutic strategies for treating pain and substance use disorders, insights into mechanisms of pain and drug addiction, and the development of new behavioral models to treat substance use disorders. Original research articles, short communications, and review articles are welcomed.

Dr. Samuel Obeng
Prof. Dr. Christopher R. McCurdy
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • addiction
  • substance use disorder
  • pain
  • opioids
  • cannabinoids
  • stimulants
  • depressants
  • hallucinogens

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Published Papers (2 papers)

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Research

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15 pages, 1394 KiB  
Article
Effects of Selective and Mixed-Action Kappa and Delta Opioid Receptor Agonists on Pain-Related Behavioral Depression in Mice
by S. Stevens Negus, Celsey M. St. Onge, Young K. Lee, Mengchu Li, Kenner C. Rice and Yan Zhang
Molecules 2024, 29(14), 3331; https://doi.org/10.3390/molecules29143331 - 16 Jul 2024
Viewed by 873
Abstract
We recently developed a series of nalfurafine analogs (TK10, TK33, and TK35) that may serve as non-addictive candidate analgesics. These compounds are mixed-action agonists at the kappa and delta opioid receptors (KOR and DOR, respectively) and produce antinociception in a mouse warm-water tail-immersion [...] Read more.
We recently developed a series of nalfurafine analogs (TK10, TK33, and TK35) that may serve as non-addictive candidate analgesics. These compounds are mixed-action agonists at the kappa and delta opioid receptors (KOR and DOR, respectively) and produce antinociception in a mouse warm-water tail-immersion test while failing to produce typical mu opioid receptor (MOR)-mediated side effects. The warm-water tail-immersion test is an assay of pain-stimulated behavior vulnerable to false-positive analgesic-like effects by drugs that produce motor impairment. Accordingly, this study evaluated TK10, TK33, and TK35 in a recently validated assay of pain-related behavioral depression in mice that are less vulnerable to false-positive effects. For comparison, we also evaluated the effects of the MOR agonist/analgesic hydrocodone (positive control), the neurokinin 1 receptor (NK1R) antagonist aprepitant (negative control), nalfurafine as a selective KOR agonist, SNC80 as a selective DOR agonist, and a nalfurafine/SNC80 mixture. Intraperitoneal injection of dilute lactic acid (IP lactic acid) served as a noxious stimulus to depress vertical and horizontal locomotor activity in male and female ICR mice. IP lactic acid-induced locomotor depression was alleviated by hydrocodone but not by aprepitant, nalfurafine, SNC80, the nalfurafine/SNC80 mixture, or the KOR/DOR agonists. These results suggest that caution is warranted in advancing mixed-action KOR/DOR agonists as candidate analgesics. Full article
(This article belongs to the Special Issue Novel Chemical and Biological Agents in the Treatment of Pain and Substance Use Disorders)
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Review

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21 pages, 1406 KiB  
Review
Are There Prevalent Sex Differences in Psychostimulant Use Disorder? A Focus on the Potential Therapeutic Efficacy of Atypical Dopamine Uptake Inhibitors
by Melinda Hersey, Mattingly K. Bartole, Claire S. Jones, Amy Hauck Newman and Gianluigi Tanda
Molecules 2023, 28(13), 5270; https://doi.org/10.3390/molecules28135270 - 7 Jul 2023
Cited by 3 | Viewed by 2378
Abstract
Psychostimulant use disorders (PSUD) affect a growing number of men and women and exert sizable public health and economic burdens on our global society. Notably, there are some sex differences in the onset of dependence, relapse rates, and treatment success with PSUD observed [...] Read more.
Psychostimulant use disorders (PSUD) affect a growing number of men and women and exert sizable public health and economic burdens on our global society. Notably, there are some sex differences in the onset of dependence, relapse rates, and treatment success with PSUD observed in preclinical and clinical studies. The subtle sex differences observed in the behavioral aspects of PSUD may be associated with differences in the neurochemistry of the dopaminergic system between sexes. Preclinically, psychostimulants have been shown to increase synaptic dopamine (DA) levels and may downregulate the dopamine transporter (DAT). This effect is greatest in females during the high estradiol phase of the estrous cycle. Interestingly, women have been shown to be more likely to begin drug use at younger ages and report higher levels of desire to use cocaine than males. Even though there is currently no FDA-approved medication, modafinil, a DAT inhibitor approved for use in the treatment of narcolepsy and sleep disorders, has shown promise in the treatment of PSUD among specific populations of affected individuals. In this review, we highlight the therapeutic potential of modafinil and other atypical DAT inhibitors focusing on the lack of sex differences in the actions of these agents. Full article
(This article belongs to the Special Issue Novel Chemical and Biological Agents in the Treatment of Pain and Substance Use Disorders)
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