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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 Mu-type opioid receptor Gβ Gγ γ-Aminobutyric acid Normethadone Ca+ Ca+ Na+ Na+ γ-Aminobutyric acid Normethadone Normethadone ATP cAMP PPi GTP Guanine nucleotide- binding protein G(i) subunit alpha-1 Magnesium Normethadone depresses neurons in the cough centre of the brainstem Less GABA leads to disinhibition of dopamine cell firing in the spinal chord pain transmission neurons. This leads to the suppression of the cough centre of the brain Decreased calcium levels lead to decreased neurotransmitter release. Less GABA is released for synaptic vesicles. Normethadone 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 Normethadone is taken orally 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 OPRM1 GNB1 GNG2 γ-Aminobutyric acid Normethadone Calcium Calcium Sodium Sodium γ-Aminobutyric acid Normethadone Normethadone Adenosine triphosphate cAMP Pyrophosphate Guanosine triphosphate GNAI1