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Neuro–Endocrine–Immune Dysfunction in the Chronic Pain Patient
Published in Sahar Swidan, Matthew Bennett, Advanced Therapeutics in Pain Medicine, 2020
The increased intracellular concentration of Ca2+ promotes the externalization of phospholipases to the cell membrane which then cleave arachidonic acid and is acted upon by cyclooxygenase to produce prostanoids. Prostaglandins act pre- and post-synaptically. The pre-synaptic effect enhances the opening of voltage gated calcium channels. Post-synaptically, glycine receptors are inhibited. Glycine typically acts as an inhibitory neurotransmitter on the second-order neuron.
Neurotransmitters and Receptors, Ion Channels, G Proteins and Second Messengers
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Glycine is an inhibitory amino acid found in the CNS. The glycine receptor has a pentameric structure. It mediates postsynaptic inhibition in the spinal cord by opening chloride channels. Strychnine is an antagonist and produces convulsions.
Autoimmune disorders that can be mistaken for viral illness
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Maxwell Greene, Eric Lancaster
The glycine receptor is homologous to the GABAAR receptor, but expressed predominantly in the brainstem and spinal cord. Glycine antibodies have been reported predominantly in patients with stiff person syndrome and related disorders [34,35]. As discussed in Section 27.2.5, the PERM phenotype is particularly linked to glycine receptor antibodies. Options for commercial testing of glycine receptor antibodies are still limited, but these antibodies should be suspected in a patient with encephalitis and marked startle responses, rigidity, and/or myoclonus.
Novel Sunifiram-carbamate hybrids as potential dual acetylcholinesterase inhibitor and NMDAR co-agonist: simulation-guided analogue design and pharmacological screening
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Khalid A. Agha, Nader E. Abo-Dya, Abdul Rashid Issahaku, Clement Agoni, Mahmoud E. S. Soliman, Eatedal H. Abdel-Aal, Zakaria K. Abdel-Samii, Tarek S. Ibrahim
Full activation of NMDARs requires agonist binding at two glycine and two glutamates on the tetrameric complex. Several experimental studies showed that the glycine site was likely to be fully occupied in vivo either by glycine itself or by D-serine.16 On the other hand, it was found that at some locations in the central nervous system, the glycine site is not fully saturated by glycine due to the activity of high-affinity glycine transporters (GlyT-1).17 The requirement for occupation of the glycine site has been derived from a number of observations that blocking glycine site in NMDAR exacerbates psychotic symptoms in schizophrenic individuals and impairs cognitive performance in healthy individuals.18 As a result of this, glycine binding site has attracted attention of many scientists as a potential target for safely elevating the activity of NMDARs.19 A number of potential strategies for enhancing NMDAR function and hence improving cognition via the glycine site had developed like administration of glycine but this strategy is limited by the high activity of GlyT-1, so effort is moved to develop GlyT-1 inhibitors like Pfizer sarcosine analogue CP-802079 (Figure 2). Limitation of this approach is activation of inhibitory glycine receptors.17,20 Another promising approach involves exogenous administration of partial agonists like Sunifiram.21,22
Strychnine, old still actual poison: description of poisoning cases reported to French Poison Control Centers over the past thirteen years
Published in Toxin Reviews, 2022
Camille Paradis, Denis Dondia, Audrey Nardon, Ingrid Blanc-Brisset, Arnaud Courtois, Jules-Antoine Vaucel, Magali Labadie
In the gray matter of the spinal cord, Renshaw cells function as inhibitory interneurons associated with an alpha motor neuron. Renshaw cells receive excitatory collaterals from the alpha motor neurone and thus, upon excitation, could release glycine to the alpha motor neurone in order to exert an inhibitory feedback and prevent alpha motor neurone firing. Strychnine is a potent antagonist of glycine receptors thus acting as an inhibitor of an inhibitory signal. This results in a motor disturbance characterized by an increase in muscle tone, associated with muscular hyperactivity. Clinical symptoms of poisoning appear suddenly and rapidly after ingestion, and begin with painful muscle contractures spontaneous or triggered by even the slightest stimulus, trismus, an opisthotonus (a position which the whole body is arched backward in hyperextension) and generalized convulsions for the severe forms. Importantly, during the course of poisoning, consciousness is retained. The clinical picture is complicated by major acidosis and rhabdomyolysis. Death occurs due to the paralysis of respiratory muscles or a cardiac arrest (Baud and Garnier 2017).
An analytical strategy for the identification of carbamates, toxic alkaloids, phenobarbital and warfarin in stomach contents from suspected poisoned animals by thin-layer chromatography/ultraviolet detection
Published in Toxicology Mechanisms and Methods, 2019
André Valle de Bairros, Diulia Dias, André Bezerra, Roger Wagner, Bruna Klein, Glaucia Kommers, Eliza Stefanon, Ana Miguel Pego
Other toxic agents such as alkaloids from Nux vomica, mainly strychnine and brucine (STY and BRU), are considered classic rodenticides. These alkaloids act as antagonists of the glycine receptor, increasing glycine levels in the synaptic cleft and promoting large muscle contractions and violent convulsions. Death occurs by asphyxiation due to paralysis of central nervous system respiration control and/or exhaustive seizure (Melo and Silva Junior 2005; Cowan and Blakley 2015). Methomyl (MET) and carbofuran (CAR) are pesticides from the carbamate class, considered cholinesterase enzyme inhibitors and responsible for the increase in acetylcholine levels in muscarinic and nicotinic receptors. As a consequence, sweating, salivation and difficulty breathing are some of toxic effects that can progress to respiratory failure and even death (Eddleston and Konickx 2014; Gonçalves et al. 2017). In order to perform toxicological analysis on these xenobiotics, chromatographic methods are commonly used, such as thin-layer chromatography (TLC) (Stahr et al. 1981; Rengel and Friedrich 1993; Cazenave et al. 2005; Xavier et al. 2007; Kuwayama et al. 2012).