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α-Pyrrolidinooctanophenone facilitates activation of human microglial cells via ROS/STAT3-dependent pathway.
Forensic Toxicol
December 2024
Laboratory of Bioinformatics, Gifu Pharmaceutical University, Gifu, 502-8585, Japan.
Purpose: Pyrrolidinophenone derivatives (PPs) are amphetamine-like designer drugs containing a pyrrolidine ring, and their adverse effects resemble those of methamphetamine (METH). Microglial activation has been recently suggested as a key event in eliciting the adverse effects against dysfunction of the central nervous system. The aim of this study is to clarify the mechanisms of microglial activation induced by PPs.
View Article and Find Full Text PDFComparative Effectiveness of Buprenorphine/Naloxone and Methadone on Methamphetamine/Amphetamine Use Among People with Opioid Use Disorder in Canada.
Subst Use Addctn J
November 2024
British Columbia Centre on Substance Use, Vancouver, BC, Canada.
Article Synopsis
- The study investigates the impact of opioid agonist therapy (OAT) on methamphetamine and amphetamine use among individuals with opioid use disorder (OUD) in Canada, comparing buprenorphine/naloxone and methadone.
- Conducted over 24 weeks, data from a pan-Canadian trial highlighted that both treatments showed no significant effect on reducing methamphetamine/amphetamine use, as assessed through drug testing and self-reporting.
- Despite methamphetamine/amphetamine use being prevalent among participants, results indicated that neither treatment method led to notable changes in their usage patterns throughout the study period.
Effects of the kappa-opioid receptor antagonist nor-binaltorphimine on methamphetamine-vs-food choice in male rhesus monkeys.
Drug Alcohol Depend
January 2025
Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, NIDA and NIAAA, Bethesda, MD, USA.
Background: Kappa-opioid receptors (KOR) are hypothesized to be involved in mediating ongoing methamphetamine self-administration. Previous rat studies have demonstrated that treatment with the KOR antagonist nor-binaltorphimine (nor-BNI) decreases methamphetamine self-administration. However, KOR antagonist effects on methamphetamine self-administration in nonhuman primates are unknown.
View Article and Find Full Text PDFInhibitory effects of the selective μ-opioid receptor antagonist UD-030 on methamphetamine-induced conditioned place preference.
Neuropsychopharmacol Rep
March 2025
Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Although methamphetamine (METH) and other addictive substance use disorders are a major social problem worldwide, appropriate pharmacotherapies have not yet been discovered. Subtype-nonselective opioid receptor antagonists, such as naltrexone (NTX), have been reported to suppress METH addiction, but unclear are the opioid receptor subtypes that are involved in this beneficial effect. To clarify the role of μ-opioid receptors (MOPs), we examined effects of the novel nonpeptidic MOP-selective antagonist UD-030 on the acquisition and expression of METH-induced conditioned place preference (CPP) using behavioral tests in C57BL/6J mice.
View Article and Find Full Text PDFAmphetamine Derivatives as Potent Central Nervous System Multitarget SERT/NET/H Agents: Synthesis and Biological Evaluation.
Molecules
November 2024
School of Pharmacy, Nanjing Tech University, 30th South Puzhu Road, Nanjing 211816, China.
In this research, a variety of novel amphetamine derivatives were synthesized and assessed for their potential as multifaceted antidepressant agents. Among these compounds, compound demonstrated potent inhibitory effects on both serotonin and noradrenaline transporters (SERT/NET) and high affinity for histamine H receptor (HR), and displayed low affinity for off-target receptors (H1, α1) and hERG channels, which can reduce the prolongation of the QT interval. Molecular docking studies offered a rational binding model of compound when it forms a complex with SERT, NET, and the histamine H receptor.
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