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administration, resulting in flaccid paralysis (Renew, 2026) Succinylcholine's effect during Phase I block is purely postsynaptic and results from a relatively constant reduction in twitch amplitude caused by the prolonged occupancy of postsynaptic nAChRs by succinylcholine, which interferes with the normal acetylcholine-mediated neurotransmission when a motoneuron is stimulated (Figure 2)(Jonsson et al, 2006) Clinically: Equal reduction in all four twitches during train-of-four stimulation No fade pattern observed Phase II Block (Presynaptic & Open Channel Mechanisms) Occurs with abnormally high doses or repeated administration : Phase I block progresses to a state resembling non-depolarizing blockade Characterized by: Presynaptic autoreceptor antagonism Succinylcholine has been shown to antagonize neuronal 32 nACh receptors with an IC50 that is ~10-times higher than its EC50 for stimulating the muscle-type (11) nACh receptors (Freeman, 1968

Abbreviations 2,3-BPG: 2,3-Bisphosphoglyceric acid AA : Amino acid ANLS: Astrocyte-neuron lactate shuttle ATP: Adenosine triphosphate AUC: Area under the curve BBB: Bloodbrain barrier BCAA: Branched chain amino acid CCI: Controlled cortical impact CMD: Cerebral microdialysis CNS: Central nervous system coA: Coenzyme A cPLA2 : Cytosolic phospholipases A2 CSF : Cerebrospinal fluid CT : Computed tomography ETC: Electron transport chain FOXP3: Forkhead box P3 GCS: Glasgow coma scale GFAP: Glial fibrillary acidic protein GLUT: Glucose transporters GOS(E): Glasgow outcome scale (extended) GSH: Glutathione peroxidase H-NMR: Proton nuclear magnetic resonance HIF-1: Hypoxia-inducible factor-1alpha ICP: Intracranial pressure ICU: Intensive care unit IL: Interleukin iNOS: Inducible nitric oxide synthase LPC: Lysophosphatidylcholine LPR: Lactate/Pyruvate ratio LPS: Lipopolysaccharide MS: Mass spectrometry NAA: N-acetylaspartate NAD(H): Nicotinamide adenine dinucleotide NADP(H): Nicotinamide adenine dinucleotide phosphate NF-B: Nuclear factor kappa B NOX: NADPH oxidase NRF2: Nuclear factor erythroid 2-related factor 2 O-LPC: Ether lysophosphatidylcholine PbtO2: Partial pressure of brain tissue oxygen PEP: Phosphatidylethanolamines PET: Positron emission tomography PGC1a: Peroxisome proliferatoractivated receptor gamma coactivator-1 alpha ROS: Reactive oxygen species S100B: S100 calcium-binding protein B Sirt1: NAD-dependent deacetylase sirtuin-1 SM: Sphingomyelin TBI: Traumatic brain injury TCA: Citric acid cycle, krebs cycle TG: Triglyceride TIL: Therapeutic intensity level UCH-L1: Ubiquitin C-terminal hydrolase-L1 References Centers for Disease Control and Prevention

Mol Neurobiol 57(5):2314

GLP-1 receptor agonist medications are designed to mimic or activate that same pathway

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