Pain White Paper by Joseph Vaughan, M.D.
... 2012). Many of the treatments for both pain and headache are directed at the periphery (Richards, 2013), most especially for pain and topically applied medications, though central effects from transdermally used agents which have sparing absorption and low serum levels may be important as well. ...
... 2012). Many of the treatments for both pain and headache are directed at the periphery (Richards, 2013), most especially for pain and topically applied medications, though central effects from transdermally used agents which have sparing absorption and low serum levels may be important as well. ...
CURRICULUM VITAE
... Recent discovery of an allosteric binding site on the cannabinoid CB1 receptor invites new approaches to potential drugs that modulate cannabinoid signaling for therapeutic benefit. Several GPCRs have been shown to contain allosteric binding sites for endogenous/synthetic ligands which are discrete ...
... Recent discovery of an allosteric binding site on the cannabinoid CB1 receptor invites new approaches to potential drugs that modulate cannabinoid signaling for therapeutic benefit. Several GPCRs have been shown to contain allosteric binding sites for endogenous/synthetic ligands which are discrete ...
Curcumin Analogs as Anticancer Agents
... *Chakrabarti R, Rawat PS, Cooke BM, Coppel RL, Patankar S, “Cellular Effects of Curcumin on Plasmodium falciparum Include Disruption of Microtubules”. PLoS ONE, (2013), 8 (3): e57302. ...
... *Chakrabarti R, Rawat PS, Cooke BM, Coppel RL, Patankar S, “Cellular Effects of Curcumin on Plasmodium falciparum Include Disruption of Microtubules”. PLoS ONE, (2013), 8 (3): e57302. ...
A Multifaceted GABAA Receptor Modulator
... general anesthetic etomidate. The negligible activities displayed by methaqualone at numerous neurotransmitter receptors and transporters in an elaborate screening for additional putative central nervous system (CNS) targets suggest that it is a selective GABAAR modulator. The mode of action of meth ...
... general anesthetic etomidate. The negligible activities displayed by methaqualone at numerous neurotransmitter receptors and transporters in an elaborate screening for additional putative central nervous system (CNS) targets suggest that it is a selective GABAAR modulator. The mode of action of meth ...
Glucagon Receptor Agonists and Antagonists
... mRNA levels in the retina increase with plus lens wear.6 Conversely, the absence of immediate early gene production during form deprivation or negative lens wear implies minimal release of peptides from glucagon amacrine cells and suggests that the lack of glucagon is responsible for the development ...
... mRNA levels in the retina increase with plus lens wear.6 Conversely, the absence of immediate early gene production during form deprivation or negative lens wear implies minimal release of peptides from glucagon amacrine cells and suggests that the lack of glucagon is responsible for the development ...
Synopsis of Some Recent Tactical Application of Bioisosteres in
... for the mechanism-based HCV NS3 protease inhibitor telaprevir (12).39 The (S)-R-ketoamide in 12 readily racemizes at higher pH and, most notably, in human plasma to afford the(R)diastereomer, which exhibits 30-fold weaker biological activity (Figure 2). The (R)-diastereomer of 12 is the primary meta ...
... for the mechanism-based HCV NS3 protease inhibitor telaprevir (12).39 The (S)-R-ketoamide in 12 readily racemizes at higher pH and, most notably, in human plasma to afford the(R)diastereomer, which exhibits 30-fold weaker biological activity (Figure 2). The (R)-diastereomer of 12 is the primary meta ...
Selective inhibitor of LRRK2, a protein kinase
... unique because a missense mutation, G2019S, is frequently found in not only familial but also sporadic PD cases4,5. The most common and extensively characterized mutation, G2019S, enhances kinase activity, suggesting that small molecule LRRK2 kinase inhibitors may serve as potential therapeutic age ...
... unique because a missense mutation, G2019S, is frequently found in not only familial but also sporadic PD cases4,5. The most common and extensively characterized mutation, G2019S, enhances kinase activity, suggesting that small molecule LRRK2 kinase inhibitors may serve as potential therapeutic age ...
Salvinorin A: A novel and highly selective n
... (Roth et al., 2002; Chavkin et al., 2004). Salvinorin A is the main active ingredient of the hallucinogenic plant Salvia divinorum-a member of the sage family (Valdes et al., 1983; Siebert, 1994). In humans, ingestion of Salvia divinorum via mastication of a quid induces a short-lived experience whi ...
... (Roth et al., 2002; Chavkin et al., 2004). Salvinorin A is the main active ingredient of the hallucinogenic plant Salvia divinorum-a member of the sage family (Valdes et al., 1983; Siebert, 1994). In humans, ingestion of Salvia divinorum via mastication of a quid induces a short-lived experience whi ...
I The 1982 John
... antagonists, and antagonist analgesics. In addition to naloxone, these studies focus on two cfosely related compounds, nalbuphine and naltrexone. Nalbuphine is an antagonist analgesic that is practically as potent as morphine when injected.3Z3.3 But because of its antagonist properties, it carries l ...
... antagonists, and antagonist analgesics. In addition to naloxone, these studies focus on two cfosely related compounds, nalbuphine and naltrexone. Nalbuphine is an antagonist analgesic that is practically as potent as morphine when injected.3Z3.3 But because of its antagonist properties, it carries l ...
6-keto, 7,8
... Fentanyl is a μ agonist with about 80 times the poyency of morphine. The advantages of fentanyl over morphine for anesthetic procedures are its short duration of action (1to 2 hours). A fentenyl patch has been released for the treatment of severe chronic pain. Fentanyl’s short duration of acti ...
... Fentanyl is a μ agonist with about 80 times the poyency of morphine. The advantages of fentanyl over morphine for anesthetic procedures are its short duration of action (1to 2 hours). A fentenyl patch has been released for the treatment of severe chronic pain. Fentanyl’s short duration of acti ...
Butorphanol-Mediated Antinociception in Mice: Partial Agonist
... effects of agonists, but it is typically used in situations in which it is not possible to redetermine an agonist dose-effect curve in the presence of multiple doses of the antagonist (e.g., limited supply of the antagonist). In the present study, these analyses are used to compare the analgesic eff ...
... effects of agonists, but it is typically used in situations in which it is not possible to redetermine an agonist dose-effect curve in the presence of multiple doses of the antagonist (e.g., limited supply of the antagonist). In the present study, these analyses are used to compare the analgesic eff ...
8 Ultra-low-dose opioid antagonists enhance opioid analgesia while
... reduction in opioid-related side effects. The side effects of opiates include nausea, vomiting, pruritus, insomnia, constipation, sedation and impaired physical function (Ballantyne and Mao, 2003). In many cases, patients taking opioids are balancing side effects with analgesia, often choosing to to ...
... reduction in opioid-related side effects. The side effects of opiates include nausea, vomiting, pruritus, insomnia, constipation, sedation and impaired physical function (Ballantyne and Mao, 2003). In many cases, patients taking opioids are balancing side effects with analgesia, often choosing to to ...
... aspartate 113, serine 204, serine 207 and phenylalanine 290, known from molecular biology studies on genetically engineered recombinant point-mutated receptors to be crucial for ligand binding [21–24]. The binding of adrenaline to key amino acid residues in the active site of the beta2-adrenoceptor ...
assessment of the opiate properties of two constituents of a toxic
... (MPTP) and 1-methyl-4-phenyl-4-propionoxypiperidine (MPPP). The opiate properties of these two compounds have been assessed using in vitro receptor binding techniques as well as behavioral tests indicative of opiate action, including analgesia, catatonia, respiratory depression and the loss of right ...
... (MPTP) and 1-methyl-4-phenyl-4-propionoxypiperidine (MPPP). The opiate properties of these two compounds have been assessed using in vitro receptor binding techniques as well as behavioral tests indicative of opiate action, including analgesia, catatonia, respiratory depression and the loss of right ...
Protein Kinase C Mediates the Synergistic Interaction Between
... between intrathecally administered ␣2AR and opioid agonists is well documented, but the mechanism underlying this synergy remains unclear. The delta-opioid receptor (DOP) and the ␣2AARs are coexpressed on the terminals of primary afferent fibers in the spinal cord where they may mediate this phenome ...
... between intrathecally administered ␣2AR and opioid agonists is well documented, but the mechanism underlying this synergy remains unclear. The delta-opioid receptor (DOP) and the ␣2AARs are coexpressed on the terminals of primary afferent fibers in the spinal cord where they may mediate this phenome ...
Cannabinoids for Gastrointestinal Diseases: Potential Therapeutic
... that include plant-derived cannabinoids and synthetic analogues of these compounds. Of these, ∆9-THC, ∆8-THC and cannabinol are constituents of marijuana, whereas HU-210 (11-hydroxy-∆8-THC-demethylheptyl) is a synthetic cannabinoid. ∆9-THC and ∆8-THC bind both CB1 and CB2 receptors at submicromolar ...
... that include plant-derived cannabinoids and synthetic analogues of these compounds. Of these, ∆9-THC, ∆8-THC and cannabinol are constituents of marijuana, whereas HU-210 (11-hydroxy-∆8-THC-demethylheptyl) is a synthetic cannabinoid. ∆9-THC and ∆8-THC bind both CB1 and CB2 receptors at submicromolar ...
An Introduction to Medicinal Chemistry
... There can be little doubt that alcohol is a drug and as such causes society more problems than all other drugs put together. One only has to study road accident statistics to appreciate that fact. It has been stated that if alcohol was discovered today, it would be restricted in exactly the same way ...
... There can be little doubt that alcohol is a drug and as such causes society more problems than all other drugs put together. One only has to study road accident statistics to appreciate that fact. It has been stated that if alcohol was discovered today, it would be restricted in exactly the same way ...
ACNE
... SMT D002 is a new promising and potentially safe medication (Oxybutynin chloride), it has successfully completed two Phase I trials in healthy volunteers and believed to treat seborrhoea, a symptom of Parkinson's disease and the primary cause of acne. Topical formulation of the drug is currently bei ...
... SMT D002 is a new promising and potentially safe medication (Oxybutynin chloride), it has successfully completed two Phase I trials in healthy volunteers and believed to treat seborrhoea, a symptom of Parkinson's disease and the primary cause of acne. Topical formulation of the drug is currently bei ...
Salvinorin A, an Active Component of the Hallucinogenic Sage
... using either G␣16 (A and B) or Gq-i5 (C and D). No responses were seen in untransfected cells or in cells transfected with hKOR alone (data not shown). Figure 2 also shows a representative dose-response study using Gq-i5 as the chimeric G protein. Because both methods seemed to yield equivalent resu ...
... using either G␣16 (A and B) or Gq-i5 (C and D). No responses were seen in untransfected cells or in cells transfected with hKOR alone (data not shown). Figure 2 also shows a representative dose-response study using Gq-i5 as the chimeric G protein. Because both methods seemed to yield equivalent resu ...
... Direct inhibition of 5-LO, partly through an iron-catalysed redox mechanism, has been achieved with compounds such as benzofurans (L-670,630 and L-650,224), hydroxamates (BWA4C), N-hydroxyurea derivatives (A64077 or zileuton) and indazolinones (ICI 207,968), with good selectivity and potency [49]. I ...
Minireview The Neurokinin-1 Receptor in Addictive Processes
... contrast to the effects that are typically observed with CRH-R1 antagonism. CRH-R1 inhibitors generally show anxiolysis only under conditions in which anxiety has been elevated, such as after stress, drug withdrawal, or genetic selection for increased anxiety (Heilig and Koob, 2007; Rotzinger et al. ...
... contrast to the effects that are typically observed with CRH-R1 antagonism. CRH-R1 inhibitors generally show anxiolysis only under conditions in which anxiety has been elevated, such as after stress, drug withdrawal, or genetic selection for increased anxiety (Heilig and Koob, 2007; Rotzinger et al. ...
HERE - INDIGO Biosciences
... extracted from PDB entry 1NQ1 ([4-(4-hydroxy-3-iodo-phenoxy)-3,5diiodo-phenyl]-acetic acid) with Tanimoto Combo index of 0.68 and EON_ShapeTanimoto index of 0.54 (Fig. 1), and high similarity to T3 with Tanimoto Combo index of 0.52 and EON_ShapeTanimoto index of 0.42. The docking analysis was carrie ...
... extracted from PDB entry 1NQ1 ([4-(4-hydroxy-3-iodo-phenoxy)-3,5diiodo-phenyl]-acetic acid) with Tanimoto Combo index of 0.68 and EON_ShapeTanimoto index of 0.54 (Fig. 1), and high similarity to T3 with Tanimoto Combo index of 0.52 and EON_ShapeTanimoto index of 0.42. The docking analysis was carrie ...
Pharmacological Significance of Synthetic Heterocycles
... fundamental manifestations of life as the provision of energy, transmission of nerve impulses, sight, metabolism and the transfer of hereditary information are all based on chemical reactions involving the participation of many heterocyclic compounds, such as vitamins, enzymes, coenzymes, nucleic ac ...
... fundamental manifestations of life as the provision of energy, transmission of nerve impulses, sight, metabolism and the transfer of hereditary information are all based on chemical reactions involving the participation of many heterocyclic compounds, such as vitamins, enzymes, coenzymes, nucleic ac ...
AN OVERVIEW OF CAPSICUM
... species (capsaicin and dihydrocapsaicin) were also tested for their anti-microbial effects. or their antimicrobial effects with fifteen bacterial species and one yeast species.While it’s biological function is to repel herbivores animals and fungi.Capsicum is derived from the Greek word "Kapsimo" me ...
... species (capsaicin and dihydrocapsaicin) were also tested for their anti-microbial effects. or their antimicrobial effects with fifteen bacterial species and one yeast species.While it’s biological function is to repel herbivores animals and fungi.Capsicum is derived from the Greek word "Kapsimo" me ...
Discovery and development of TRPV1 antagonists
Relief from chronic pain remains a recognized unmet medical need. Consequently, the search for new analgesic agents is being intensively studied by the pharmaceutical industry. The TRPV1 receptor is an ion channel that has been implicated in mediation of many types of pain and therefore studied most extensively. The first competitive antagonist, capsazepine, was first described in 1990, since then development of novel TRPV1 antagonists has come a long way. This effort has led to the identification of several TRPV1 antagonists that have entered clinical trials as analgesic agents. Should these new chemical entities relieve symptoms of chronic pain then this class of compounds may offer one of the first novel mechanisms for the treatment of pain, in many years.