Drug discrimination studies for assessment of psychoactive properties of drugs in safety pharmacology and drug abuse and drug dependence potential evaluation have traditionally been focused on testing novel compounds against standard drugs for which drug abuse has been documented, e.g. opioids, CNS stimulants, cannabinoids etc. (e.g. Swedberg & Giarola, 2015), and results are interpreted such that the extent to which the test drug causes discriminative effects similar to those of the standard training drug, the test drug would be further characterized as a potential drug of abuse. Regulatory guidance for preclinical assessment of abuse liability by the European Medicines Agency (EMA, 2006), the U.S. Food and Drug Administration (FDA, 2010), the International Conference of Harmonization (ICH, 2009), and the Japanese Ministry of Health Education and Welfare (MHLW, 1994) detail that compounds with central nervous system (CNS) activity, whether by design or not, need abuse and dependence liability assessment. Therefore, drugs with peripheral targets and a potential to enter the CNS, as parent or metabolite, are also within scope (see Swedberg, 2013, for a recent review and strategy). Compounds with novel mechanisms of action present a special challenge due to unknown abuse potential, and should be carefully assessed against defined risk criteria. Apart from compounds sharing mechanisms of action with known drugs of abuse, compounds intended for indications currently treated with drugs with potential for abuse and or dependence are also within scope, regardless of mechanism of action. Examples of such compounds are analgesics, anxiolytics, cognition enhancers, appetite control drugs, sleep control drugs and drugs for psychiatric indications. Recent results (Swedberg et al., 2014; Swedberg & Raboisson, 2014; Swedberg, 2015) on the metabotropic glutamate receptor type 5 (mGluR5) antagonists demonstrate that compounds causing hallucinatory effects in humans did not exhibit clear discriminative effects when tested against classical drugs of abuse in drug discrimination studies, and were not self-administered by rats. However, these compounds did cause salient discriminative effects of their own in animals trained to discriminate them from no drug. Therefore, from a safety pharmacology perspective, novel compounds that do not cause discriminative effects similar to classical drugs of abuse, may still cause psychoactive effects in humans and carry the potential to maintain drug abuse, suggesting that proactive investigation of drug abuse potential is warranted (Swedberg, 2013). These and other findings will be discussed, and the application of drug discrimination procedures beyond the typical standard application of testing novel compounds against known and well characterized reference drugs will be addressed.
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http://dx.doi.org/10.1016/j.vascn.2016.05.011 | DOI Listing |
Infect Disord Drug Targets
January 2025
HCA Healthcare Las Palmas/Del Sol Internal Medicine Program.
Background: Streptococcal Toxic Shock Syndrome (STSS) is a life-threatening condition caused by bacterial toxins. The STSS triad encompasses high fever, hypotensive shock, and a "sunburn-like" rash with desquamation. STSS, like Toxic Shock Syndrome (TSS), is a rare complication of streptococcal infec-tions caused by Group A Streptococcus (GAS), Streptococcal pyogenes (S.
View Article and Find Full Text PDFObjective: Our objective of this study was to analyse all oncological clinical trials using regorafenib to create a complete risk/benefit profile for the drug.
Background: Creating a novel chemotherapy is costly both in time and capital spent for drug manufacturers. To regenerate what they've spent, drug manufacturers may attempt to repurpose their medications for new indications via clinical trials.
Forensic Toxicol
January 2025
Morgue Department, Council of Forensic Medicine, Istanbul, Turkey.
Purpose: The analysis of drug residues on some currencies is well-established in the literature. However, there is no published study describing the presence of drug residues on Turkish paper currency.
Methods: This study focused on the analysis of 14 drug residues present on 600 Turkish banknotes collected from three different cities: Ankara, Adana, and Istanbul.
Arch Sex Behav
January 2025
Department of Public Administration, School of Politics and Public Administration, Guangxi Normal University, Guilin, 541006, Guangxi, China.
Abuse of new drugs, such as Rush poppers, methamphetamine, Magu, Ketamine, and Ecstasy, is common among men who have sex with men (MSM) in China, leading to increased risks of sexually explicit media consumption, sexual violence, and sexual risk behaviors. This study aimed to explore the prevalence and relationships of these behaviors among MSM with new drug abuse. A cross-sectional study was conducted from January to June 2021, involving 453 MSM in Jinan, China.
View Article and Find Full Text PDFJ Neuroimmunol
January 2025
Immunology Laboratory, Department of Biomedical Engineering, Indian Institute of Technology Ropar, Rupnagar 140001, Punjab, India. Electronic address:
Morphine is a globally prevalent substance of misuse, renowned for its immunosuppressive effects mediated through opioid receptors expressed on immune cells. Macrophages are crucial antigen-presenting cells that fulfill diverse roles, such as antigen presentation, phagocytosis, wound healing, and disease protection. They are typically classified based on their activation states: M1 (proinflammatory), M2 (anti-inflammatory), and M0 (resting).
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