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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
O
2
5-Hydroxy-L-tryptophan
4a-Hydroxytetrahydrobiopterin
CO
2
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
O
2
5-HTP
4aHtHbp
CO
2
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