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D(2) dopamine receptor 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 Sodium- dependent dopamine transporter Synaptic vesicular amine transporter Aromatic-L- amino-acid decarboxylase Tyrosine 3-monooxygenase Dopamine Ca+ Clozapine Ca+ Dopamine Dopamine Clozapine L-Dopa CO2 L-Tyrosine Tetrahydrobiopterin O2 Dihydrobiopterin H2O Na+ Na+ Pyridoxal 5'-phosphate Gi signaling cascade Fe2+ Cytosol Postsynaptic Neuron Presynaptic Neuron Cytosol Synaptic Vesicle Synapse Clozapine is a D2 receptor antagonist. Dopamine receptors in the mesolimbic pathway are responsible for producing the positive symptoms in schizophrenia ↓ Positive, negative and cognitive symptoms of schizophrenia Brain Mesolimbic pathway Blood-Brain Barrier Diffusion Clozapine is taken orally and absorbed from the gastrointestinal tract When action potential arrives to the nerve terminal, calcium channels open causing influx of calcium ions which trigger the release of dopamine via exocytosis. Excess dopamine in the brain triggers positive symptoms of schizophrenia
DRD2 CACNA1A CACNB1 CACNA2D2 SLC6A3 SLC18A2 DDC TH Dopamine Calcium Clozapine Calcium Dopamine Dopamine Clozapine L-Dopa Carbon dioxide L-Tyrosine Tetrahydrobiopterin Oxygen Dihydrobiopterin Water Sodium Sodium Gi signaling cascade
DRD2 CACNA1A CACNB1 CACNA2D2 SLC6A3 SLC18A2 DDC TH LDP Ca+ Clozapi Ca+ LDP LDP Clozapi L-Dopa CO2 Tyr BH4 O2 BH3 H2O Na+ Na+ Pyr-5'P Gi si c Fe2+ Cytosol Postsynaptic Neuron Presynaptic Neuron Cytosol Synaptic Vesicle Synapse Clozapine is a D2 receptor antagonist. Dopamine receptors in the mesolimbic pathway are responsible for producing the positive symptoms in schizophrenia ↓ Positive, negative and cognitive symptoms of schizophrenia Brain Mesolimbic pathway Blood-Brain Barrier Diffusion Clozapine is taken orally and absorbed from the gastrointestinal tract When action potential arrives to the nerve terminal, calcium channels open causing influx of calcium ions which trigger the release of dopamine via exocytosis. Excess dopamine in the brain triggers positive symptoms of schizophrenia