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Dissociation between the anti-allodynic effects of fingolimod (FTY720) and desensitization of S1P receptor-mediated G-protein activation in a mouse model of sciatic nerve injury.
Neuropharmacology
December 2024
Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. Electronic address:
Sphingosine-1-phosphate (S1P) receptor (S1PR) agonists, such as fingolimod (FTY720), alleviate nociception in preclinical pain models by either activation (agonism) or inhibition (functional antagonism) of S1PR type-1 (S1PR1). However, the dose-dependence and temporal relationship between reversal of nociception and modulation of S1PR1 signaling has not been systematically investigated. This study examined the relationship between FTY720-induced antinociception and S1PR1 adaptation using a sciatic nerve chronic constriction injury (CCI) model of neuropathic pain in male and female C57Bl/6J mice.
View Article and Find Full Text PDFKetamine can produce oscillatory dynamics by engaging mechanisms dependent on the kinetics of NMDA receptors.
Proc Natl Acad Sci U S A
May 2024
Department of Mathematics and Statistics, Boston University, Boston, MA 02215.
Ketamine is an N-methyl-D-aspartate (NMDA)-receptor antagonist that produces sedation, analgesia, and dissociation at low doses and profound unconsciousness with antinociception at high doses. At high and low doses, ketamine can generate gamma oscillations (>25 Hz) in the electroencephalogram (EEG). The gamma oscillations are interrupted by slow-delta oscillations (0.
View Article and Find Full Text PDFInfluence of intravenous fentanyl or dexmedetomidine infusions, combined with lidocaine and ketamine, on cardiovascular response, sevoflurane requirement and postoperative pain in dogs anesthetized for unilateral mastectomy.
Vet Anaesth Analg
June 2024
Faculty of Veterinary Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Objective: To compare the effects of constant rate infusions (CRI) of fentanyl or dexmedetomidine, combined with lidocaine and ketamine, on cardiovascular response during surgery, sevoflurane requirement and postoperative pain in dogs undergoing mastectomy.
Study Design: Prospective, randomized, blinded, clinical trial.
Animals: A total of 29 female dogs with mammary tumors.
Ketamine can produce oscillatory dynamics by engaging mechanisms dependent on the kinetics of NMDA receptors.
bioRxiv
April 2024
Department of Mathematics and Statistics, Boston University, Boston, MA 02215.
Article Synopsis
- * It produces gamma oscillations in the brain's electrical activity (EEG), which can be disrupted by slow-delta oscillations at high doses; however, the link between subcellular actions and these network-level oscillations is still unclear.
- * By developing a biophysical model, researchers have demonstrated how ketamine's impact on NMDA receptors can influence brain oscillations, revealing new mechanisms for its anesthetic effects and potential use in treating depression.
Discovery of a Potent Highly Biased MOR Partial Agonist among Diastereomeric C9-Hydroxyalkyl-5-phenylmorphans.
Molecules
June 2023
Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services, 9800 Medical Center Drive, Bethesda, MD 20892-3373, USA.
All possible diastereomeric C9-hydroxymethyl-, hydroxyethyl-, and hydroxypropyl-substituted 5-phenylmorphans were synthesized to explore the three-dimensional space around the C9 substituent in our search for potent MOR partial agonists. These compounds were designed to lessen the lipophilicity observed with their C9-alkenyl substituted relatives. Many of the 12 diastereomers that were obtained were found to have nanomolar or subnanomolar potency in the forskolin-induced cAMP accumulation assay.
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