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5- hydroxytryptamine receptor 2A 5- hydroxytryptamine receptor 2C Alpha-1A adrenergic receptor Beta-1 adrenergic receptor Beta-2 adrenergic receptor Sodium- dependent serotonin transporter Sodium- dependent noradrenaline transporter Voltage- dependent P/Q-type calcium channel subunit alpha-1A Voltage- dependent L-type calcium channel subunit beta-1 Voltage- dependent calcium channel subunit alpha-2/delta-2 Synaptic vesicular amine transporter Voltage- dependent P/Q-type calcium channel subunit alpha-1A Voltage- dependent L-type calcium channel subunit beta-1 Voltage- dependent calcium channel subunit alpha-2/delta-2 Synaptic vesicular amine transporter Solute carrier organic anion transporter family member 1A2 Aromatic-L- amino-acid decarboxylase Dopamine beta- hydroxylase Tyrosine 3-monooxygenase Tryptophan 5-hydroxylase 1 Aromatic-L- amino-acid decarboxylase Cytochrome P450 1A2 Cytochrome P450 2C19 Cytochrome P450 3A4 Ca+ Norepinephrine Ca+ Serotonin Serotonin Norepinephrine Clomipramine Desmethylclomipramine Ca+ Norepinephrine Ca+ Serotonin Clomipramine Clomipramine Desmethylclomipramine Desmethylclomipramine Clomipramine Clomipramine Desmethylclomipramine L-Dopa Dopamine CO2 Ascorbic acid O2 Dehydroascorbic acid H2O L-Tyrosine Tetrahydrobiopterin O2 Dihydrobiopterin H2O L-Tryptophan Tetrahydrobiopterin O2 5-Hydroxy-L-tryptophan 4a-Hydroxytetrahydrobiopterin CO2 O2 NADH Formaldehyde NAD H2O Pyridoxal 5'-phosphate Pyrroloquinoline quinone Copper Fe2+ Fe2+ Pyridoxal 5'-phosphate Heme Heme Heme Gq signaling cascade Gq signaling cascade Gs signaling cascade Cytosol Postsynaptic Neuron Presynaptic Neuron Cytosol Synaptic Vesicle Synaptic Vesicle Cytosol Cytosol Presynaptic Neuron Postsynaptic Neuron Synapse Synapse Mood Improvement Serotonin is synthesized and stored in synaptic vesicles at the nerve terminal Clomipramine inhibits the serotonin reuptake transporter, thereby increasing synaptic serotonin Serotonin activates 5HT2A and 5HT2C receptors, which are responsible for mood improvements Norepinephrine is synthesized and stored in synaptic vesicles at the nerve terminal Desmethylclomipramine inhibits the norepinephrine reuptake transporter, thereby increasing synaptic norepinephrine levels Mood Improvement Norepinephrine activates post synaptic adrenergic receptors which are responsible for mood improvements Hepatocyte Liver Blood-Brain Barrier Diffusion Diffusion
Endoplasmic Reticulum HTR2A HTR2C ADRA1A ADRB1 ADRB2 SLC6A4 SLC6A2 CACNA1A CACNB1 CACNA2D2 SLC18A2 CACNA1A CACNB1 CACNA2D2 SLC18A2 SLCO1A2 DDC DBH TH TPH1 DDC CYP1A2 CYP2C19 CYP3A4 Calcium Norepinephrine Calcium Serotonin Serotonin Norepinephrine Clomipramine Desmethylclomipramine Calcium Norepinephrine Calcium Serotonin Clomipramine Clomipramine Desmethylclomipramine Desmethylclomipramine Clomipramine Clomipramine Desmethylclomipramine L-Dopa Dopamine Carbon dioxide Ascorbic acid Oxygen Dehydroascorbic acid Water L-Tyrosine Tetrahydrobiopterin Oxygen Dihydrobiopterin Water L-Tryptophan Tetrahydrobiopterin Oxygen 5-Hydroxy-L- tryptophan 4a- Hydroxytetrahydrobiopterin Carbon dioxide Oxygen NADH Formaldehyde NAD Water Gq signaling cascade Gq signaling cascade Gs signaling cascade
HTR2A HTR2C ADRA1A ADRB1 ADRB2 SLC6A4 SLC6A2 CACNA1A CACNB1 CACNA2D2 SLC18A2 CACNA1A CACNB1 CACNA2D2 SLC18A2 SLCO1A2 DDC DBH TH TPH1 DDC CYP1A2 CYP2C19 CYP3A4 Ca+ Norpp Ca+ 5-HT 5-HT Norpp Clomipr Desmtcp Ca+ Norpp Ca+ 5-HT Clomipr Clomipr Desmtcp Desmtcp Clomipr Clomipr Desmtcp L-Dopa LDP CO2 VitC O2 DHAA H2O Tyr BH4 O2 BH3 H2O Trp BH4 O2 5-HTP 4aHtHbp CO2 O2 NADH Formol NAD H2O Pyr-5'P Pqq Cu Fe2+ Fe2+ Pyr-5'P Heme Heme Heme Gq si c Gq si c G s c Cytosol Postsynaptic Neuron Presynaptic Neuron Cytosol Synaptic Vesicle Synaptic Vesicle Cytosol Cytosol Presynaptic Neuron Postsynaptic Neuron Synapse Synapse Mood Improvement Serotonin is synthesized and stored in synaptic vesicles at the nerve terminal Clomipramine inhibits the serotonin reuptake transporter, thereby increasing synaptic serotonin Serotonin activates 5HT2A and 5HT2C receptors, which are responsible for mood improvements Norepinephrine is synthesized and stored in synaptic vesicles at the nerve terminal Desmethylclomipramine inhibits the norepinephrine reuptake transporter, thereby increasing synaptic norepinephrine levels Mood Improvement Norepinephrine activates post synaptic adrenergic receptors which are responsible for mood improvements Hepatocyte Liver Blood-Brain Barrier Diffusion Diffusion
Endoplasmic Reticulum HTR2A HTR2C ADRA1A ADRB1 ADRB2 SLC6A4 SLC6A2 CACNA1A CACNB1 CACNA2D2 SLC18A2 CACNA1A CACNB1 CACNA2D2 SLC18A2 SLCO1A2 DDC DBH TH TPH1 DDC CYP1A2 CYP2C19 CYP3A4 Ca2+ Norpp Ca2+ 5-HT 5-HT Norpp Clomipr Desmtcp Ca2+ Norpp Ca2+ 5-HT Clomipr Clomipr Desmtcp Desmtcp Clomipr Clomipr Desmtcp L-Dopa LDP CO2 VitC O2 DHAA H2O Tyr BH4 O2 BH3 H2O Trp BH4 O2 5-HTP 4aHtHbp CO2 O2 NADH Formol NAD H2O Gq si c Gq si c G s c