Revisiting AMPA receptors as an antiepileptic drug target
... However, repetitive activation of AMPA receptors can cause sufficient depolarization to relieve the magnesium block, enabling a slower NMDA receptor mediated component of the response that is associated with calcium influx into the postsynaptic neuron. This influx triggers various forms of synaptic ...
... However, repetitive activation of AMPA receptors can cause sufficient depolarization to relieve the magnesium block, enabling a slower NMDA receptor mediated component of the response that is associated with calcium influx into the postsynaptic neuron. This influx triggers various forms of synaptic ...
Revisiting AMPA Receptors as an Antiepileptic Drug Target
... However, repetitive activation of AMPA receptors can cause sufficient depolarization to relieve the magnesium block, enabling a slower NMDA receptor mediated component of the response that is associated with calcium influx into the postsynaptic neuron. This influx triggers various forms of synaptic ...
... However, repetitive activation of AMPA receptors can cause sufficient depolarization to relieve the magnesium block, enabling a slower NMDA receptor mediated component of the response that is associated with calcium influx into the postsynaptic neuron. This influx triggers various forms of synaptic ...
Ligand Residence Time at G-protein–Coupled Receptors—Why We
... we will refer the reader to those articles or the recently published book Thermodynamics and Kinetics of Drug Binding (Keserü and Swinney, 2015) for an in-depth discussion, and we will focus on the concept of residence time at GPCRs. The signal transduction cascade that is mediated by a GPCR is init ...
... we will refer the reader to those articles or the recently published book Thermodynamics and Kinetics of Drug Binding (Keserü and Swinney, 2015) for an in-depth discussion, and we will focus on the concept of residence time at GPCRs. The signal transduction cascade that is mediated by a GPCR is init ...
Phyto Lec 16
... 2 types of compounds; either semi-synthetic from morphine structure by 1)replacing OHs on the 3&6 positions most properly get morphine agonist "with similar activity, lower side effects, more potent than morphine" or 2)substituting on N most properly get morphine antagonist. Here we have new termino ...
... 2 types of compounds; either semi-synthetic from morphine structure by 1)replacing OHs on the 3&6 positions most properly get morphine agonist "with similar activity, lower side effects, more potent than morphine" or 2)substituting on N most properly get morphine antagonist. Here we have new termino ...
... Other properties of this drug are less well characterized. Pharmacological studies have identified epinastine as a 5-HT2 antagonist, probably due to its structural resemblance to other guanidines which have been shown to be peripherally acting 5-HT2 antagonists [1]. Epinastine has been shown to bloc ...
Identification of novel natural compound inhibitors for human
... crucial and classic manifestation of the inflammatory process, neuropathic pain can arise from any of multiple nerve lesions or diseases, with symptoms including hyperalgesia or allodynia (Kidd, 2001; Baron et al., 2010). Even painkillers, like opioids and nonsteroidal anti-inflammatory drugs (NSAID ...
... crucial and classic manifestation of the inflammatory process, neuropathic pain can arise from any of multiple nerve lesions or diseases, with symptoms including hyperalgesia or allodynia (Kidd, 2001; Baron et al., 2010). Even painkillers, like opioids and nonsteroidal anti-inflammatory drugs (NSAID ...
Terms and symbols - Guide to Pharmacology
... chemical signaling between and within cells. Combination of a hormone, neurotransmitter, drug, or intracellular messenger with its receptor(s) initiates a change in cell function. Thus NC-IUPHAR does not classify simple binding sites, without function (although truncated proteins without signaling f ...
... chemical signaling between and within cells. Combination of a hormone, neurotransmitter, drug, or intracellular messenger with its receptor(s) initiates a change in cell function. Thus NC-IUPHAR does not classify simple binding sites, without function (although truncated proteins without signaling f ...
New Insights for Drug Design from the X
... possible the recent solution of X-ray structures of pharmaceutically important G protein-coupled receptors (GPCRs), including receptors for biogenic amines, peptides, a nucleoside, and a sphingolipid. These high-resolution structures have greatly increased our understanding of ligand recognition and ...
... possible the recent solution of X-ray structures of pharmaceutically important G protein-coupled receptors (GPCRs), including receptors for biogenic amines, peptides, a nucleoside, and a sphingolipid. These high-resolution structures have greatly increased our understanding of ligand recognition and ...
Opioids
... modulating effect of -opioid receptor (MOR)– mediated analgesia on descending pathways. • The pain-inhibitory neuron is indirectly activated by opioids (exogenous or endogenous), which inhibit an inhibitory (GABAergic) interneuron. • This results in enhanced inhibition of nociceptive processing in ...
... modulating effect of -opioid receptor (MOR)– mediated analgesia on descending pathways. • The pain-inhibitory neuron is indirectly activated by opioids (exogenous or endogenous), which inhibit an inhibitory (GABAergic) interneuron. • This results in enhanced inhibition of nociceptive processing in ...
The Influence of Conformational Isomerism on Drug
... have an increased duration of action over the parent compound in addition to the above stated advantages. Even though this is an idealized case, it is not that far-fetched. Small, conformationally flexible neurotransmitters such as acetylcholine, norepinephrine and histamine are known to bind in dif ...
... have an increased duration of action over the parent compound in addition to the above stated advantages. Even though this is an idealized case, it is not that far-fetched. Small, conformationally flexible neurotransmitters such as acetylcholine, norepinephrine and histamine are known to bind in dif ...
Body Temperature and Analgesic Effects of Selective Mu and Kappa
... blocked or antagonized by selective kappa receptor antagonists (Cavicchini et al., 1988; Handler et al., 1992). On the basis of findings such as these, we hypothesized that the hyperthermic response to opioids is mediated by the mu receptor and the hypothermic response is mediated by the kappa recep ...
... blocked or antagonized by selective kappa receptor antagonists (Cavicchini et al., 1988; Handler et al., 1992). On the basis of findings such as these, we hypothesized that the hyperthermic response to opioids is mediated by the mu receptor and the hypothermic response is mediated by the kappa recep ...
Large Receptor Reserve for Cannabinoid Actions in the Central
... and receptor reserve in biological systems has been to progressively inactivate an increasing percentage of the receptors using an irreversibly binding antagonist and to measure the resultant effects on the functional dose-response curve for the ligand investigated, along with concomitant measuremen ...
... and receptor reserve in biological systems has been to progressively inactivate an increasing percentage of the receptors using an irreversibly binding antagonist and to measure the resultant effects on the functional dose-response curve for the ligand investigated, along with concomitant measuremen ...
Effects of ()-HA-966, CGS-19755, Phencyclidine, and Dizocilpine on
... key lights, a correct response turned all the keys blue and a correct response in the presence of the blue key lights produced a 0.5-s flash of the hopper light and restarted the cycle in red. On the fifth time through the cycle (FR5), a correct response in the presence of the blue light resulted in ...
... key lights, a correct response turned all the keys blue and a correct response in the presence of the blue key lights produced a 0.5-s flash of the hopper light and restarted the cycle in red. On the fifth time through the cycle (FR5), a correct response in the presence of the blue light resulted in ...
Atypical Neuroleptics Enhance Histamine Turnover in Brain Via 5
... completely reversed it at the presynaptic H3 receptor with an IC50 value of 10 6 3 mM (Fig. 2). Taking into account an EC50 value of 0.06 mM for exogenous HA (Garbarg et al., 1992), an apparent Ki value of 0.6 mM was calculated for clozapine acting as an H3-receptor antagonist in this functional mod ...
... completely reversed it at the presynaptic H3 receptor with an IC50 value of 10 6 3 mM (Fig. 2). Taking into account an EC50 value of 0.06 mM for exogenous HA (Garbarg et al., 1992), an apparent Ki value of 0.6 mM was calculated for clozapine acting as an H3-receptor antagonist in this functional mod ...
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... groups of therapeutic agents. NSAIDs are widely used in the treatment of rheumatoid arthritis and inflammatory diseases. However, long-term NSAID use has been associated with gastrointestinal (GI) ulceration, bleeding and nephrotoxicity (Kimmey, 1992). The tendency of many acidic drugs to accumulate ...
... groups of therapeutic agents. NSAIDs are widely used in the treatment of rheumatoid arthritis and inflammatory diseases. However, long-term NSAID use has been associated with gastrointestinal (GI) ulceration, bleeding and nephrotoxicity (Kimmey, 1992). The tendency of many acidic drugs to accumulate ...
Histamine receptor antagonists
... are longer-acting, with duration of action of 12–24 hours. The newer agents are considerably less lipid-soluble than the first-generation drugs and are substrates of the P-glycoprotein transporter in the blood-brain barrier; as a result they enter the central nervous system with difficulty or not at ...
... are longer-acting, with duration of action of 12–24 hours. The newer agents are considerably less lipid-soluble than the first-generation drugs and are substrates of the P-glycoprotein transporter in the blood-brain barrier; as a result they enter the central nervous system with difficulty or not at ...
this PDF file - Journal of the Indian Institute of Science
... and membranes containing opiate receptorsL1: (1) A non-specific saturable binding consisting primarily of interactions between thc protonated nitrogen atom of Lhe opiate and anionic group:, of monbrntlc niacromolecules. (2) A non-saturable interaction (trapped and disaolvcd) having the physical soht ...
... and membranes containing opiate receptorsL1: (1) A non-specific saturable binding consisting primarily of interactions between thc protonated nitrogen atom of Lhe opiate and anionic group:, of monbrntlc niacromolecules. (2) A non-saturable interaction (trapped and disaolvcd) having the physical soht ...
Best Practice Management of CINV in Oncology Patients: I
... Although response rates in individual trials comparing firstgeneration 5-HT3 receptor antagonists sometimes differed, overall efficacy of these agents are similar in the settings of HEC and MEC.7 Palonosetron is a second-generation 5-HT3 receptor antagonist with a half-life of approximately 40 hours ...
... Although response rates in individual trials comparing firstgeneration 5-HT3 receptor antagonists sometimes differed, overall efficacy of these agents are similar in the settings of HEC and MEC.7 Palonosetron is a second-generation 5-HT3 receptor antagonist with a half-life of approximately 40 hours ...
NMDA Receptor Antagonists
... versus NS nasal spray placebo during closure. VAS scores Nicotine grp: 44-5 VAS scores Placebo grp: 77 -8 Analgesic effects last 24 hours despite 45 minute kinetics lifespan of nasal nicotine. Flood P, Daniel D. Intranasal nicotine for postoperative pain treatment. Anesthesiology. 2004; 101:14 ...
... versus NS nasal spray placebo during closure. VAS scores Nicotine grp: 44-5 VAS scores Placebo grp: 77 -8 Analgesic effects last 24 hours despite 45 minute kinetics lifespan of nasal nicotine. Flood P, Daniel D. Intranasal nicotine for postoperative pain treatment. Anesthesiology. 2004; 101:14 ...
HST-151
... drugs are called "parasympathomimetic". Antagonists of muscarinic transmission have roughly the opposite actions, and are called "parasympatholytic" agents. ...
... drugs are called "parasympathomimetic". Antagonists of muscarinic transmission have roughly the opposite actions, and are called "parasympatholytic" agents. ...
Title: Directly observable behavioral effects of lorcaserin in rats
... Lorcaserin has highest affinity for 5-HT2C receptors, although it also binds to other 5-HT receptor subtypes and at still higher concentrations to the 5-HT transporter (Thomsen et al., 2008). It is well established that many of the behavioral effects of lorcaserin are mediated by agonist activity at ...
... Lorcaserin has highest affinity for 5-HT2C receptors, although it also binds to other 5-HT receptor subtypes and at still higher concentrations to the 5-HT transporter (Thomsen et al., 2008). It is well established that many of the behavioral effects of lorcaserin are mediated by agonist activity at ...
DOPAMINE ANTAGONISTS: PHENOTHIAZINE/THIOXANTHENE SAR
... symptoms) or tuberoinfundibular (prolactin release). They also bind with varying affinities on nondopaminergic sites, such as cholinergic (muscarinic), alpha-1adrenergic and histamine-1 receptors, which can partially explain the varied side effect profiles for each agent. Typical antipsychotics have ...
... symptoms) or tuberoinfundibular (prolactin release). They also bind with varying affinities on nondopaminergic sites, such as cholinergic (muscarinic), alpha-1adrenergic and histamine-1 receptors, which can partially explain the varied side effect profiles for each agent. Typical antipsychotics have ...
... experimental conditions no interaction between cholinergic and NANC responses was involved. In each bronchial ring, following a first series (control) of transmural EFS of 1–32 Hz, a second series was performed 60 min later with or without (vehicle) fenspiride (10-6 to 10-4 M) added to the bath 15 m ...
patrick_ch22_p1
... imidazole binding region and two polar binding regions Two binding modes are proposed - one for agonists and one for antagonists The imidazole binding region is common to both binding modes One of the polar binding regions is accessed by agonists and the other by antagonists The antagonist polar reg ...
... imidazole binding region and two polar binding regions Two binding modes are proposed - one for agonists and one for antagonists The imidazole binding region is common to both binding modes One of the polar binding regions is accessed by agonists and the other by antagonists The antagonist polar reg ...
Allosteric Modulation: a Novel Approach to Drug Discovery
... for GPCR Targets That Historically have Evaded Small Molecule Drug Developers Several GPCR targets are currently thought to be beyond the reach of conventional competitive drug discovery approaches due to the complexity of the interaction of the endogenous ligand with the receptor – including, for e ...
... for GPCR Targets That Historically have Evaded Small Molecule Drug Developers Several GPCR targets are currently thought to be beyond the reach of conventional competitive drug discovery approaches due to the complexity of the interaction of the endogenous ligand with the receptor – including, for e ...
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.