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Beta-1 adrenergic receptor Sodium- dependent noradrenaline transporter Alpha-1A adrenergic receptor Synaptic vesicular amine transporter Voltage- dependent calcium channel subunit alpha-2/delta-1 Voltage- dependent calcium channel subunit alpha-2/delta-2 Voltage- dependent N-type calcium channel subunit alpha-1B Multidrug resistance protein 1 Dopamine beta- hydroxylase Aromatic-L- amino-acid decarboxylase Tyrosine 3-monooxygenase Norepinephrine Milnacipran Ca+ Norepinephrine Norepinephrine Ca+ Milnacipran Milnacipran Dopamine Ascorbic acid O2 Dehydroascorbic acid H2O L-Dopa CO2 L-Tyrosine Pyrroloquinoline quinone Copper Pyridoxal 5'-phosphate Fe2+ Gq Signalling cascade Limbic System Alpha-1-adrenoceptor- mediated activation of inhibitory interneurons, direct alpha-2-adrenergic action on pain-relay neurons Limbic System Brain Emotions Cognition Cytosol Presynaptic Neuron The inhibition of norepinephrine reuptake receptors by milnacipran causes more norepinephrine to accumulate in the synapse, causing the continual activation of the alpha-1A adrenergic receptor Synapse Synaptic Vesicle Milnacipran is rapidly absorbed from the gastrointestinal tract. Norepinephrine is produced in the locus coeruleus Cytosol In depressed individuals, B1 and A1 adrenergic receptors are desensitized leading to changes in cognitive function, fatigue, sleep and immune response. Blood vessel - blood brain barrier
ADRB1 SLC6A2 ADRA1A SLC18A2 CACNA2D1 CACNA2D2 CACNA1B ABCB1 DBH DDC TH Norepinephrine Milnacipran Calcium Norepinephrine Norepinephrine Calcium Milnacipran Milnacipran Dopamine Ascorbic acid Oxygen Dehydroascorbic acid Water L-Dopa Carbon dioxide L-Tyrosine Gq Signalling cascade
ADRB1 SLC6A2 ADRA1A SLC18A2 CACNA2D1 CACNA2D2 CACNA1B ABCB1 DBH DDC TH Norpp F2207 Ca+ Norpp Norpp Ca+ F2207 F2207 LDP VitC O2 DHAA H2O L-Dopa CO2 Tyr Pqq Cu Pyr-5'P Fe2+ Gq Si c Limbic System Alpha-1-adrenoceptor- mediated activation of inhibitory interneurons, direct alpha-2-adrenergic action on pain-relay neurons Limbic System Brain Emotions Cognition Cytosol Presynaptic Neuron The inhibition of norepinephrine reuptake receptors by milnacipran causes more norepinephrine to accumulate in the synapse, causing the continual activation of the alpha-1A adrenergic receptor Synapse Synaptic Vesicle Milnacipran is rapidly absorbed from the gastrointestinal tract. Norepinephrine is produced in the locus coeruleus Cytosol In depressed individuals, B1 and A1 adrenergic receptors are desensitized leading to changes in cognitive function, fatigue, sleep and immune response. Blood vessel - blood brain barrier
ADRB1 SLC6A2 ADRA1A SLC18A2 CACNA2D1 CACNA2D2 CACNA1B ABCB1 DBH DDC TH Norpp F2207 Ca2+ Norpp Norpp Ca2+ F2207 F2207 LDP VitC O2 DHAA H2O L-Dopa CO2 Tyr Gq Si c