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5- hydroxytryptamine receptor 2A 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 Sodium- dependent serotonin transporter Tryptophan 5-hydroxylase 1 Aromatic-L- amino-acid decarboxylase Ca+ Serotonin Serotonin Clozapine Ca+ Serotonin Clozapine L-Tryptophan Tetrahydrobiopterin O2 5-Hydroxy-L-tryptophan 4a-Hydroxytetrahydrobiopterin CO2 Na+ Na+ Fe2+ Pyridoxal 5'-phosphate Gq signaling cascade Synaptic Vesicle Cytosol Cytosol Presynaptic Neuron Postsynaptic Neuron Synapse ↓ Negative symptoms of schizophrenia Serotonin is synthesized and stored in synaptic vesicles at the nerve terminal Clozapine binds to 5HT2A where it acts as a functional antagonist to reduce negative symptoms of schizophrenia Brain Blood-Brain Barrier Diffusion Clozapine taken orally is absorbed from the gastrointestinal tract
HTR2A CACNA1A CACNB1 CACNA2D2 SLC18A2 SLC6A4 TPH1 DDC Calcium Serotonin Serotonin Clozapine Calcium Serotonin Clozapine L-Tryptophan Tetrahydrobiopterin Oxygen 5-Hydroxy-L- tryptophan 4a- Hydroxytetrahydrobiopterin Carbon dioxide Sodium Sodium Gq signaling cascade
HTR2A CACNA1A CACNB1 CACNA2D2 SLC18A2 SLC6A4 TPH1 DDC Ca+ 5-HT 5-HT Clozapi Ca+ 5-HT Clozapi Trp BH4 O2 5-HTP 4aHtHbp CO2 Na+ Na+ Fe2+ Pyr-5'P Gq si c Synaptic Vesicle Cytosol Cytosol Presynaptic Neuron Postsynaptic Neuron Synapse ↓ Negative symptoms of schizophrenia Serotonin is synthesized and stored in synaptic vesicles at the nerve terminal Clozapine binds to 5HT2A where it acts as a functional antagonist to reduce negative symptoms of schizophrenia Brain Blood-Brain Barrier Diffusion Clozapine taken orally is absorbed from the gastrointestinal tract
HTR2A CACNA1A CACNB1 CACNA2D2 SLC18A2 SLC6A4 TPH1 DDC Ca2+ 5-HT 5-HT Clozapi Ca2+ 5-HT Clozapi Trp BH4 O2 5-HTP 4aHtHbp CO2 Na+ Na+ Gq si c