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Adenylate cyclase type 2 GABAA receptor Gamma- aminobutyric acid type B receptor N-type calcium channel G protein- activated inward rectifier potassium channel 1 Substance-P receptor ATP-binding cassette sub-family C member 3 Solute carrier family 22 member 1 ATP-binding cassette sub-family C member 3 Cytochrome P450 2D6 UDP- glucuronosyltransferase 2B7 Mu-type opioid receptor γ-Aminobutyric acid Substance P Morphine Codeine-6-glucuronide cAMP Ca+ Ca+ Na+ Na+ γ-Aminobutyric acid Morphine Morphine Morphine Codeine Codeine Codeine-6-glucuronide Codeine-6-glucuronide Codeine-6-glucuronide ATP PPi O2 NADH H2O Formaldehyde NAD UDP-D-galacturonate UDP H+ Heme GTP Pain Guanine nucleotide- binding protein G(i) subunit alpha-1 Magnesium Less GABA leads to disinhibition of dopamine cell firing in the spinal chord pain transmission neurons. This leads to analgesia and less pain signalling Decreased calcium levels lead to decreased neurotransmitter release. Less GABA is released for synaptic vesicles. Morphine and codeine-6-glucouronide activate presynaptic mu opioid type receptors in the dorsal root ganglion The Gi subunit of the mu opioid receptor activates the inwardly rectifying potassium channel increasing K+ conductance. This causes membrane hyperpolarization decreasing the chances of neuronal firing/action potential. Post-Synaptic Neuron Pre-Synaptic Neuron Synapse Cytosol Synaptic Vesicle The mu opioid receptor through the gamma subunit inhibits voltage gated N-type calcium channels stopping the influx of calcium into the neuron. Morphine acts at A delta and C pain fibres in the dorsal horn of the spinal chord. By decreasing neurotransmitter action there is less pain transmittance into the spinal chord. This leads to less pain perception. C Pain Fibres The inhibition of adenylate cyclase prevents the production of cAMP which further prevents depolarization and pain signalling Substance P is also not released into the synapse which prevents the activation of pain signalling. Codeine is usually given orally, but can also be given subcutaneously or through and intramuscular shot. Only 5% of codeine is metabolized into morphine, the majority is metabolized into codeine-6-glucuronide which is the main active metabolite Hepatocyte Liver
Endoplasmic Reticulum ADCY2 GABRG2 GABBR1 CACNA1B KCNJ3 TACR1 ABCC3 SLC22A1 ABCC3 CYP2D6 UGT2B7 OPRM1 GNB1 GNG2 γ-Aminobutyric acid Substance P Morphine Codeine-6- glucuronide cAMP Calcium Calcium Sodium Sodium γ-Aminobutyric acid Morphine Morphine Morphine Codeine Codeine Codeine-6- glucuronide Codeine-6- glucuronide Codeine-6- glucuronide Adenosine triphosphate Pyrophosphate Oxygen NADH Water