Two parallel synthetic methods were developed to explore the structure-activity relationships (SAR) of a series of potent opioid agonists. This series of tropanylidene benzamides proved extremely tolerant of structural variation while maintaining excellent opioid activity. Evaluation of several representative compounds from this series in the mouse hot plate test revealed potent antinociceptive effects upon oral administration.
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http://dx.doi.org/10.1016/j.bmcl.2004.09.004 | DOI Listing |
Contemp Clin Trials Commun
February 2025
Dept. of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI, USA.
Background: In people with substance use disorders (SUDs), stress-exposure can impair executive function, and increase craving and likelihood of drug-use recurrence. Research shows that acute stressors increase drug-seeking behavior; however, mechanisms underlying this effect are incompletely understood. The Competing Neurobehavioral Decisions System theory posits that persons with SUDs may have hyperactive limbic reward circuitry and hypoactive executive control circuitry.
View Article and Find Full Text PDFPharmacol Res
January 2025
Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada; Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada; RECITAL International Partnership Lab, Université de Caen-Normandie, Caen, France & Université de Sherbrooke, Sherbrooke, QC, Canada. Electronic address:
β-arrestins play pivotal roles in seven transmembrane receptor (7TMR) signalling and trafficking. To study their functional role in regulating specific receptor systems, current research relies mainly on genetic tools, as few pharmacological options are available. To address this issue, we designed and synthesised a novel lipidated phosphomimetic peptide inhibitor targeting β-arrestins, called ARIP, which was developed based on the C-terminal tail (A343-S371) of the vasopressin V2 receptor.
View Article and Find Full Text PDFBr J Pharmacol
January 2025
Center for Clinical Pharmacology, Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA.
Background And Purpose: Pituitary adenylate cyclase activating polypeptide (PACAP) is a human migraine trigger that is being targeted for migraine. The δ-opioid receptor (δ-receptor) is a novel target for the treatment of migraine, but its mechanism remains unclear. The goals of this study were to develop a mouse PACAP-headache model using clinically significant doses of PACAP; determine the effects of δ-receptor activation in this model; and investigate the co-expression of δ-receptors, PACAP and PACAP-PAC1 receptor.
View Article and Find Full Text PDFReg Anesth Pain Med
January 2025
Psychiatry, Yale School of Medicine, West Haven, Connecticut, USA
Drug Alcohol Depend
January 2025
British Columbia Centre on Substance Use, 1045 Howe St Suite 400, Vancouver, British Columbia V6Z 2A9, Canada; Interdepartmental Division of Addiction Medicine, St. Paul's Hospital, 1081 Burrard Street, Vancouver, British Columbia, V6Z 1Y6.
Background: People exposed to fentanyl may report that the dose of methadone in the commonly accepted therapeutic range feels too low. We examined self-reported methadone dose adequacy.
Methods: We conducted a retrospective cohort study of individuals prescribed methadone at a dose of at least 60mg daily using data from three community-recruited prospective cohort studies of people who use drugs in Vancouver, Canada from December 2016 through March 2020.
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