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Three Key Neurotransmitter Systems
of Antidepressants
• Norepinephrine• Dopamine• Serotonine
NOREPINEPHRINE RECEPTORS
presynaptic alpha 2 autoreceptor
postsynaptic alpha 2
receptorpostsynaptic beta 1 receptor
alpha 1 receptor
5-19 Stahl S M, Essential Psychopharmacology (2000)
DOPAMINE RECEPTORS
presynaptic autorecptor
D1 D2 D3 D4 D5
dopamine transporter
5--33 Stahl S M, Essential Psychopharmacology (2000)
SEROTONIN RECEPTORS
alpha 2 hetero receptor
5HT1D autoreceptor
5HT1A
serotonin transporter
5HT2A5HT2C
5HT3 5HT45HTX
5HTY
5HTZ
5--36 Stahl S M, Essential Psychopharmacology (2000)
SSRI Pharmacological Profile
Powerful 5HT disinhibition in key passways• from midbrain raphe to prefrontal cortex• from midbrain raphe to basal ganglia• from midbrain raphe to limbic cortex and
hippocampus• from midbrain raphe to hypothalamus• from midbrain raphe to spinal cord
Serotonin Pathways
Raphe Nucleus
5--51 Stahl S M, Essential Psychopharmacology (2000)
5--52 Stahl S M, Essential Psychopharmacology (2000)
Frontal Cortex Mood
5--53 Stahl S M, Essential Psychopharmacology (2000)
Basal Ganglia OCDAkathisia/Agitation
5--54 Stahl S M, Essential Psychopharmacology (2000)
Limbic Anxiety
5--55 Stahl S M, Essential Psychopharmacology (2000)
Hypothalamus Appetite/bulimia
5--56 Stahl S M, Essential Psychopharmacology (2000)
Sleep Centers Insomnia
SEROTONIN RECEPTORS
alpha 2 hetero receptor
5HT1D autoreceptor
5HT1A
serotonin transporter
5HT2A5HT2C
5HT3 5HT45HTX
5HTY
5HTZ
5--36 Stahl S M, Essential Psychopharmacology (2000)
NOREPINEPHRINE RECEPTORS
presynaptic alpha 2 autoreceptor
postsynaptic alpha 2
receptorpostsynaptic beta 1 receptor
alpha 1 receptor
5-19 Stahl S M, Essential Psychopharmacology (2000)
serotonin neuron
presynaptic alpha 2 autoreceptor
postsynaptic alpha 2 hetero receptor
presynaptic alpha 2 autoreceptor alpha 1
receptor
norepinephrine neuron
5--48 Stahl S M, Essential Psychopharmacology (2000)
5HT accelerator
5HT brake
7-11 Stahl S M, Essential Psychopharmacology (2000)
5HT1A
anxiolyticanti- depressant
5HT2C
anxiolytic
weight gain
5HT2A anxiolyticsleep restoring
no sexual dysfunction
5HT3
no GI problems
no nausea
SRI
NRIM1
H1
TCA
6-27 Stahl S M, Essential Psychopharmacology (2000)
• 5-HT1A
• Antidepressant• Anxiolytic• Lowering temperature
SRI inserted
NRI inserted
depression lifts
6-28 6-29
Stahl S M, Essential Psychopharmacology (2000)
depression lifts
H1 inserted
M1 inserted
LAXATIVE
constipation
dry mouth
blurred vision
drowsiness
6-30 6-31
Stahl S M, Essential Psychopharmacology (2000)
weight gain
drowsiness
inserteddizziness
decreased blood pressure
6-32 Stahl S M, Essential Psychopharmacology (2000)