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N-type calcium channel potassium voltage-gated channel subfamily J Adenylate cyclase type 2 GABAA receptor Gamma- aminobutyric acid type B receptor ATP-binding cassette sub-family C member 3 Cytochrome P450 2D6 Mu-type opioid receptor Gβ Gγ γ-Aminobutyric acid Dihydromorphine cAMP Dihydromorphine Dihydromorphine Dihydromorphine Ca+ Ca+ Na+ Na+ γ-Aminobutyric acid Dihydrocodeine Dihydrocodeine ATP PPi Heme GTP Pain Guanine nucleotide- binding protein G(i) subunit alpha-1 Magnesium Dihydromorphine is released into the blood where it travels to the brain. Dihydrocodeine is metabolized into morphine in the liver through P450 enzymes. Dihydromorphine 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 Hepatocyte Endoplasmic Reticulum Liver Less GABA leads to disinhibition of dopamine cell firing in the spinal chord pain transmission neurons. This leads to less pain signalling and analgesia Decreased calcium levels lead to decreased neurotransmitter release. Less GABA is released for synaptic vesicles. Dihydromorphine binds to pre synaptic mu opioid type receptors. 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. Blood-Brain Barrier Diffusion Dihydrocodeine is taken orally through a capsule, tablet, or syrup With the inhibition of adenylate cyclase, it is unable to synthesize cAMP which further prevents calcium from entering the neuron and depolarization of the neuron
CACNB1 KCNJ9 ADCY2 GABRG2 GABBR1 ABCC3 CYP2D6 OPRM1 GNB1 GNG2 γ-Aminobutyric acid Dihydromorphine cAMP Dihydromorphine Dihydromorphine Dihydromorphine Calcium Calcium Sodium Sodium γ-Aminobutyric acid Dihydrocodeine Dihydrocodeine Adenosine triphosphate Pyrophosphate Guanosine triphosphate Pain GNAI1