A functional link between the cannabinoid and opioid receptor pathways has been proposed based on data showing that cannabinoid effects can be blocked by opioid receptor antagonists and that cannabinoids can bind to opioid receptors. To explore this link in more detail at the receptor level, we tested the hypothesis that cannabinoids directly activate or modulate mu opioid receptor function. The G-protein coupled mu opioid receptor, MOR-1, and its effector, the G-protein activated potassium channel, GIRK2 (Kir3.2), were expressed together in Xenopus oocytes and potassium currents measured using the two-electrode voltage clamp technique. The specific mu receptor agonist DAMGO activated potassium currents in oocytes expressing the mu receptor that were fully inhibited by the mu receptor antagonist, naloxone. The endogenous cannabinoid, anandamide, and the synthetic cannabinoid, WIN 55,212-2, had no direct effects on potassium currents in the oocytes expressing the mu receptor. The cannabinoids also had no effect on the magnitude of the potassium currents activated by DAMGO or on the desensitization kinetics of MOR-1 in the continued presence of DAMGO. Both WIN 55,212-2 and anandamide activated cannabinoid CB1 receptors when co-expressed with GIRK2 in the oocytes. We conclude that neither anandamide nor WIN 55,212-2 directly activate or modulate mu opioid receptor function in oocytes and that interactions of cannabinoids with mu opioid receptors are likely to be indirect.
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http://dx.doi.org/10.1007/s00210-007-0201-7 | DOI Listing |
J Clin Anesth
December 2024
Department of Anesthesiology and Pain Medicine, Seoul National University, College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address:
Study Objective: VVZ-149 is a small molecule that inhibits the glycine transporter type 2 and the serotonin receptor 5-hydroxytryptamine 2 A. In this Phase 3 study, we investigated the efficacy and safety of VVZ-149 as a single-use injectable analgesic for treating moderate to severe postoperative pain after laparoscopic colectomy.
Design: Randomized, parallel group, double-blind, Phase 3 clinical trial (Trial no.
J Phys Chem B
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Department of Chemistry, Furman University, Greenville, South Carolina 29613, United States.
Chronic pain is a prevalent problem affecting approximately one out of every five adults in the U.S. The most effective way to treat chronic pain is with opioids, but they cause dangerous side effects such as tolerance, addiction, and respiratory depression, which makes them quite deadly.
View Article and Find Full Text PDFJ Pain Palliat Care Pharmacother
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Department of Oncology and Hematology, Klinikum Oldenburg AoR, Oldenburg, Lower Saxony, Germany.
Naldemedine is a peripheral acting µ-opioid receptor antagonist approved by the Food and Drug Administration to treat opioid-induced constipation. Concerns about side effects like opioid withdrawal prevent its widespread use, especially for cancer patients. We performed this systematic review and meta-analysis to evaluate existing safety data of naldemedine treating opioid-induced constipation following the PRISMA guidelines.
View Article and Find Full Text PDFACS Pharmacol Transl Sci
December 2024
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 E Leigh Street, Richmond, Virginia23298, United States.
The development of highly potent and selective μ opioid receptor (MOR) modulators with favorable drug-like properties has always been a focus in the opioid domain. Our previous efforts led to the discovery of a lead compound designated as NAT, a potent centrally acting MOR modulator. However, the fact that NAT precipitated considerable withdrawal effects at higher doses largely impaired its further development.
View Article and Find Full Text PDFFront Pharmacol
December 2024
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh.
Background: Schott and Hook.f. are two commonly found vegetable species of the genus , found mainly in the Asian region.
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