A5067118176- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Neuroscience and Neuropharmacology Research
- Pain Management and Opioid Use
- Receptor Mechanisms and Signaling
- Pharmacological Receptor Mechanisms and Effects
- Neurotransmitter Receptor Influence on Behavior
- Treatment of Major Depression
- Anesthesia and Pain Management
- Pharmacological Effects and Toxicity Studies
- Ion channel regulation and function
- Opioid Use Disorder Treatment
- Pediatric Pain Management Techniques
- Diet and metabolism studies
- Poisoning and overdose treatments
- Epilepsy research and treatment
- Cancer, Stress, Anesthesia, and Immune Response
- Analytical Chemistry and Chromatography
- Cancer Treatment and Pharmacology
- Musculoskeletal pain and rehabilitation
- Analytical Methods in Pharmaceuticals
- Veterinary Pharmacology and Anesthesia
- Stress Responses and Cortisol
- Pain Management and Placebo Effect
- Forensic Toxicology and Drug Analysis
Cornell University
2011-2023
American Orchid Society
2023
Weill Cornell Medicine
2020-2022
Kaiser Permanente Washington Health Research Institute
2022
Columbia University Irving Medical Center
2022
New York State Psychiatric Institute
2022
University of Genoa
2021
Neuroscience Education Institute
2021
University of Padua
2021
Acorda Therapeutics (United States)
2021
In recent years, the observation that response of patients to opioid drugs may be influenced by properties inherent in pain or syndrome, such as its pathophysiology, has evolved into belief certain types pain, e.g., neuropathic pains, unresponsive these drugs. This concept important implications for both clinical practice and basic understanding mechanisms. We critically evaluate responsiveness, particularly it relates propose a clinically relevant definition paradigm investigation. The is...
Abstract The analgesic meperidine has been reported to produce signs of central nervous system excitation in human beings. To determine the relationship between and symptoms plasma levels normeperidine, we studied 67 patients receiving for relief postoperative or chronic pain. In 48 patients, excitatory effects ranging from mild nervousness tremors, twitches, multifocal myoclonus, seizures were directly correlated with accumulation normeperidine plasma. Evidence compromised renal function...
Racemic (dl)-methadone has antagonist activity at the N-methyl-d-aspartate (NMDA) receptor. We evaluated dl-methadone, opioid active (l-) and inactive (d-) isomers in competition binding assays. dl-Methadone its d- l- exhibited low micromolar affinities for [3H]MK-801-labeled non-competitive site of NMDA receptor both rat forebrain spinal cord synaptic membranes, with Ki values displacement curves similar to those dextromethorphan, an established antagonist. They lacked affinity...
Morphine-6 beta-glucuronide is a major metabolite of morphine with potent analgesic actions. To define more fully the importance this compound in action, we have compared actions and its 6 after both peripheral central administration. Given s.c., morphine-6 elicited analgesia an effect approximately twice that due, part, to long duration action also inhibited gastrointestinal motility. Both were easily reversed by naloxone (s.c.). However, when injected either i.c.v. or intrathecally, was...
NIH Conferences17 June 2008National Institutes of Health Consensus Development Conference Statement: Hydroxyurea Treatment for Sickle Cell DiseaseFREEOtis W. Brawley, MD, Llewellyn J. Cornelius, PhD, LCSW, Linda R. Edwards, Vanessa Northington Gamble, Bettye L. Green, RN, Charles Inturrisi, Andra H. James, MPH, Danielle Laraque, Magda Mendez, Carolyn Montoya, MSN, CPNP, Brad Pollock, Lawrence Robinson, Aaron P. Scholnik, and Melissa Schori, MBA*Otis MDFrom Emory University the American...
Once daily s.c. administration of 5 mg/kg morphine, a mu-opioid agonist, or U50488H (U50), kappa 1-opioid for days in male CD-1 mice results 2-3-fold shift to the right respective analgesic (tail flick) dose-response curves, indicating development tolerance. Concurrent competitive NMDA receptor antagonist, LY274614 (LY), at 24 mg/kg/24 h infusion (osmotic pump) 6 i.p. once attenuates morphine tolerance, when response saline plus is compared on day with LY morphine. Using this paradigm,...
Concentrations of methadone in plasma, estimates pain relief, and pupillary size were determined after a single intravenous dose (10 to 30 mg) hydrochloride eight patients with chronic pain, five whom had cancer. The pharmacokinetic parameter reveal rapid extensive distribution (Varea) slow apparent elimination half-life (t½) (mean Varea = 3.59 L/kg harmonic mean t½ 23 hours). blood clearance is 106 ml/min, the renal 3.9 hepatic extraction ratio 0.089, plasma protein binding 86% 89%. These...
Ongoing interest in the improvement of pain management with opioid analgesics has led to investigation sublingual absorption. The present report determined percent absorption selected from oral cavity normal subjects under conditions controlled pH and swallowing when a 1.0 ml aliquot test drug was placed tongue for 10-minute period. Compared morphine sulfate at 6.5 (18% absorption), buprenorphine (55%), fentanyl (51%), methadone (34%) were absorbed significantly greater extent (p < 0.05),...
We measured blood concentrations of heroin and its active metabolites, 6-acetylmorphine morphine, serially in 11 patients with chronic pain (9 whom had cancer) after intravenous injection, infusion, intramuscular an oral dose hydrochloride. Parenteral provided measurable levels heroin, 6-acetylmorphine, morphine. Blood reached their maximal within minutes were cleared rapidly. The mean half-life (±S.D.) injection or infusion was only 3.0±1.3 minutes, the clearance from at apparent steady...
The ability of a competitive (LY274614; (+-)-6-phosphonomethyl-decahydroisoquinolin-3-carboxylic acid) and noncompetitive (MK801; [(+)-5 methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate) N-methyl-D-aspartate receptor antagonist to modulate the development tolerance morphine's antinociceptive (analgesic) effects was assessed by using hot-plate latency in rats. Concurrent treatment with LY274614 or MK801 continuous s.c. infusion significantly attenuated morphine...
Opioids cause constipation by binding to specific opioid receptors in the enteric and central nervous systems. First-pass glucuronidation limits systemic bioavailability of oral naloxone. This study was designed determine if naloxone could reverse opioid-induced without precipitating abstinence or recrudescence pain opioid-dependent individuals. Concentrations unmetabolized total naloxone, including glucuronide, were measured radioimmunoassay. A dose-related increase symptoms laxation...
The pharmacokinetics and the hormonal, analgesic, behavioral effects of several doses human β-endorphin were evaluated after intravenous administration to three patients intracerebroventricular one patient with pain caused by cancer. These compared hormonal intravenously administered morphine sulfate in two an enkephalin analog baboons. mean terminal half-life 5 or 10 mg was 37 min; volume distribution 178 ml/kg, metabolic clearance rate 3.2 (ml/min)/kg. cerebrospinal fluid 93 min, 0.74...
The time course of methadone in the plasma 5 maintenance subjects receiving a single daily oral dose 100 or 120 mg. has been determined. predose mean level was 0.48 fig per milliliter. peak occurred at 4 hours with an average value 0.86 This slowly declined so that 24 after administration had reached (0.46 milliliter) approximately equal to level. apparent half‐life these sub;ects 25 hours. Data on renal clearance indicate drug is partially reabsorbed by kidney and this reabsorption pH dependent.
The levels of methadone in the plasma and urine 5 subjects giaven a single oral dose 15 mg. have been determined using solvent extraction gas‐liquid chromatography. Methadone was detected 30 minutes after drug administration. peak level occurred at 4 hours followed by an exponential decline during next 20 hours. mean apparent half‐life time action methadone‐induced pupillary constriction closely coincided with course plasma. An average 52 per cent excreted as metabolites 96 Nearly one half...
Objective: The purpose of this study was to examine the effects REL-1017 (esmethadone), a novel N-methyl-d-aspartate receptor (NMDAR) channel blocker, in patients with major depressive disorder who failed benefit from one three standard antidepressant treatments their current episode. Methods: A 7-day phase 2 multicenter randomized double-blind placebo-controlled trial, comprising arms, conducted assess safety, tolerability, pharmacokinetics, and efficacy two dosages (25 mg or 50 orally once...
To determine the importance of NMDA receptor (NMDAR) in pain hypersensitivity after injury, NMDAR1 (NR1) subunit was selectively deleted lumbar spinal cord adult mice by localized injection an adenoassociated virus expressing Cre recombinase into floxed NR1 mice. mRNA and dendritic protein are reduced 80% area injection, currents, but not AMPA 86–88% lamina II neurons. The spatial knock-out does alter heat or cold paw-withdrawal latencies, mechanical threshold, motor function. However,...
The transdermal therapeutic system (fentanyl), or TTS(fentanyl), continuously delivers fentanyl for up to 72 h. (fentanyl)-100 approximately 100 micrograms/h. repeated dose pharmacokinetics of this drug using the recommended dosing interval have not been evaluated previously and were determined in present study.Blood samples obtained from ten opioid-tolerant cancer patients who received five applications TTS(fentanyl) at 72-h intervals. A sample venous blood was taken before each dose;...
The active morphine metabolite, morphine-6-glucuronide (M-6-G), may contribute to both the analgesia and adverse effects observed during (MOR) therapy. To evaluate relationship between M-6-G effects, we measured steady-state plasma concentrations of MOR concurrently noted presence or absence moderate severe cognitive impairment myoclonus in 109 cancer patients who were receiving either oral (n = 71) parenteral 38) morphine. determined by HPLC with electrochemical detection. was analyzed...
Opiate withdrawal is a common occurrence in human opiate addicts that not life threatening but hypothesized to be significant factor which may contribute drug taking behavior these dependent individuals. The purpose of this study was compare the time course for development tolerance, dependence and abstinence using rat model. Rats were made by implantation 2 morphine pellets s.c. (75 mg base). Morphine implanted rats exhibited analgesia as measured tail-dip assay, up 12 h post-implant after...