A5007922126- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Pharmacological Receptor Mechanisms and Effects
- Chemical Synthesis and Analysis
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Neuroscience and Neuropharmacology Research
- Chemical synthesis and alkaloids
- Asymmetric Synthesis and Catalysis
- Neurotransmitter Receptor Influence on Behavior
- Analytical Chemistry and Chromatography
- Synthesis of Organic Compounds
- Synthetic Organic Chemistry Methods
- Crystallography and molecular interactions
- Plant-based Medicinal Research
- Synthesis and Biological Evaluation
- Forensic Toxicology and Drug Analysis
- Carbohydrate Chemistry and Synthesis
- Alkaloids: synthesis and pharmacology
- Chemical Synthesis and Reactions
- Phenothiazines and Benzothiazines Synthesis and Activities
- Synthesis and Reactions of Organic Compounds
- Opioid Use Disorder Treatment
- Cancer Treatment and Pharmacology
- Monoclonal and Polyclonal Antibodies Research
National Institute on Drug Abuse
2012-2024
National Institute on Alcohol Abuse and Alcoholism
2011-2024
National Institutes of Health
2007-2021
Office of Extramural Research
2020-2021
Open Targets
2020-2021
Chemical Synthesis Lab
2010-2019
Center for Information Technology
2007
University of New England
2007
National Institute of Diabetes and Digestive and Kidney Diseases
1988-2006
Sapienza University of Rome
2006
Abstract The distribution of enkephalin and dynorphin immunoreactivity in the hippocampus four rodent species (gray squirrel, guinea pig, rat, hamster) is compared with pattern opiate receptor subtypes (mu, delta, kappa). opioid peptides fairly consistent anterior these species. Intense for found hilus dentate gyrus mossy fiber system. Occasional immunoreactive processes are seen molecular layer scattered throughout CA1 CA3 fields. In rat hamster, an additional plexus enkephalinergic fibers...
(+)-Naloxone was prepared in 26% overall yield eight steps from (+)-7-bromodihydrocodeinone dimethyl ketal by a synthesis which excluded enantiomeric contamination. examined three assay systems and found to have no more than 1/1000(-1)/10 000th the activity of (-)-naloxone; it can, thus, serve test stereospecificity biochemical pharmacological actions (-)-naloxone.
ABSTRACT Opioid peptides have been shown to modulate various parameters of both the humoral and cellular arms immune system. The modulatory capacity can often be substantially reduced in presence naloxone, an opioid receptor antagonist, indicating a classical ligand-receptor interaction. In order characterize these interactions further, we investigated characteristics receptors on macrophage cell line, P388d 1 . A δ-class was found with M r 58 000. We also identified MOLT-4 (T-cell) IM-9 (B...
Alkylating agents that display strong selectivity for opiate receptor types delta or mu were prepared by appropriate modification of the structures analgesics fentanyl, etonitazene, and endoethenotetrahydrooripavine. The availability these substances should facilitate studies structural basis specificity physiologic roles receptors.
Activation of Toll-like receptors has been linked to neuropathic pain and opioid dependence. (+)-Naltrexone acts as a receptor 4 (TLR4) antagonist shown reverse in rat studies. We designed synthesized compounds based on (+)-naltrexone (+)-noroxymorphone evaluated their TLR4 activities by effects inhibiting lipopolysaccharide (LPS) induced downstream nitric oxide (NO) production microglia BV-2 cells. Alteration the N-substituent gave us potent antagonist. The most promising analog,...
Vaccines against drugs of abuse have induced antibodies in animals that blocked the biological effects drug by sequestering blood and preventing it from crossing blood-brain barrier. Drugs are too small to induce and, therefore, require conjugation hapten analogs a carrier protein. The efficacy these conjugate vaccines depends on several factors including design, coupling strategy, density, protein selection, vaccine adjuvant. Previously, we shown 1 (MorHap), heroin/morphine hapten,...
An improved synthesis of a haptenic heroin surrogate 1 (6-AmHap) is reported. The intermediate needed for the preparation was described in route 2 (DiAmHap). A scalable procedure developed to install C-3 amido group. Using Boc protectng group 18 allowed an overall yield 53% from 4 and eliminated necessity preparing diamide 13. Hapten conjugated tetanus toxoid mixed with liposomes containing monophosphoryl lipid as adjuvant. vaccine induced high anti-1 IgG levels that reduced heroin-induced...
Equilibrium binding studies with the sigma receptor ligand [3H]1,3-di(2-tolyl)guanidine ([3H]DTG) demonstrated two high affinity sites in membranes prepared from guinea pig brain. The apparent Kd values of DTG for 1 and 2 were 11.9 37.6 nM, respectively. corresponding Bmax 1045 1423 fmol/mg protein. Site had (+)-pentazocine, haloperidol, (R)-(+)-PPP, carbepentane, other ligands, suggesting a similarity dextromethorphan/sigma site described by Musacchio et al. [Life Sci. 45:1721-1732 (1989)]....
Opiate receptors from NG108-15 neuroblastoma-glioma hybrid cell membranes were purified to apparent homogeneity in a form covalently labeled with the opiate affinity ligand 3-methylfentanylisothiocyanate (super-FIT). The purification procedure consists of five steps: quantitative labeling super-FIT; solubilization lubrol/3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate mixture; adsorption and elution wheat germ agglutinin-Sepharose column; immunoaffinity chromatography on columns...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBiological effects of modified colchicines. Improved preparation 2-demethylcolchicine, 3-demethylcolchicine, and (+)-colchicine reassignment the position double bond in dehydro-7-deacetamidocolchicinesManfred Roesner, Hans-Georg Capraro, Arthur E. Jacobson, Louise Atwell, Arnold Brossi, Maria A. Iorio, Thomas H. Williams, Robert Sik, Colin F. ChignellCite this: J. Med. Chem. 1981, 24, 3, 257–261Publication Date (Print):March 1, 1981Publication...
Identifying nonaddictive opioid medications is a high priority in medical science, but μ-opioid receptors (MORs) mediate both the analgesic and addictive effects of opioids. We found significant pharmacodynamic difference between morphine methadone that determined entirely by heteromerization MORs with galanin Gal1 (Gal1Rs), rendering profound decrease potency methadone. This finding was explained weaker proficiency activating dopaminergic system as compared predicted dissociation...
The mechanism by which mu ligands inhibit the binding of prototypic delta agonists to preparations brain membranes is controversial. Most investigators assume competitive inhibition. In this study, we examine interaction agonist oxymorphone and DSTLE (D-Ser2-Thr6-Leu-enkephalin) with [3H]D-Ala2-D-Leu5-enkephalin (DADL) rat brain. According two-site model, are inhibitors at both sites. allosteric model supposes that one site, noncompetitive other site. Quantitative analysis demonstrated fit...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAlterations in the stereochemistry of .kappa.-selective opioid agonist U50,488 result high-affinity .sigma. ligandsBrian R. De Costa, Wayne D. Bowen, Susan B. Hellewell, Clifford George, Richard Rothman, Audrey A. Reid, J. Michael Walker, Arthur E. Jacobson, and Kenner C. RiceCite this: Med. Chem. 1989, 32, 8, 1996–2002Publication Date (Print):August 1, 1989Publication History Published online1 May 2002Published inissue 1 August...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProbes for narcotic receptor mediated phenomena. 7. Synthesis and pharmacological properties of irreversible ligands specific .mu. or .delta. opiate receptorsTerrence R. Burke Jr., Balbir S. Bajwa, Arthur E. Jacobson, Kenner C. Rice, A. Streaty, W. KleeCite this: J. Med. Chem. 1984, 27, 12, 1570–1574Publication Date (Print):December 1, 1984Publication History Published online1 May 2002Published inissue 1 December...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDeoxymorphines: role of the phenolic hydroxyl in antinociception and opiate receptor interactionsJuergen Reden, Marvin F. Reich, Kenner C. Rice, Arthur E. Jacobson, Arnold Brossi, Richard A. Streaty, Werner KleeCite this: J. Med. Chem. 1979, 22, 3, 256–259Publication Date (Print):March 1, 1979Publication History Published online1 May 2002Published inissue 1 March...
A potential new treatment for drug addiction is immunization with vaccines that induce antibodies can abrogate the addictive effects of abuse. One challenges in development a vaccine against drugs abuse availability an optimum procedure gives reproducible and high yielding hapten-protein conjugates. In this study, heroin/morphine surrogate hapten (MorHap) was coupled to bovine serum albumin (BSA) using maleimide-thiol chemistry. MorHap-BSA conjugates 3, 5, 10, 15, 22, 28, 34 haptens were...
Active immunization is an emerging potential modality to combat fatal overdose amid the opioid epidemic. In this study, we described design, synthesis, formulation, and animal testing of efficacious vaccine against fentanyl. The formulation composed a novel fentanyl hapten conjugated tetanus toxoid (TT) adjuvanted with liposomes containing monophosphoryl lipid A adsorbed on aluminum hydroxide. linker N-phenyl-N-(1-(4-(3-(tritylthio)propanamido)phenethyl)piperidin-4-yl)propionamide were...
All possible diastereomeric C9-hydroxymethyl-, hydroxyethyl-, and hydroxypropyl-substituted 5-phenylmorphans were synthesized to explore the three-dimensional space around C9 substituent in our search for potent MOR partial agonists. These compounds designed lessen lipophilicity observed with their C9-alkenyl substituted relatives. Many of 12 diastereomers that obtained found have nanomolar or subnanomolar potency forskolin-induced cAMP accumulation assay. Almost all these fully efficacious,...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and biological evaluation of 14-alkoxymorphinans. 1. Highly potent opioid agonists in the series (-)-14-methoxy-N-methylmorphinan-6-onesHelmut Schmidhammer, Lislott Aeppli, Louise Atwell, Florian Fritsch, Arthur E. Jacobson, Michaela Nebuchla, Guenther SperkCite this: J. Med. Chem. 1984, 27, 12, 1575–1579Publication Date (Print):December 1, 1984Publication History Published online1 May 2002Published inissue 1 December...