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NSG552 / NSG 552 EXAM 1
STUDY GUIDE + REVIEW
Psychopharmacology - Wilkes
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This PDF contains:
NSG 552 EXAM 1 STUDY GUIDE
NSG 552 EXAM 1 REVIEW
Everything in Here to Pass the Exam 1
Expert-Verified
, 1
DOPAMINE
● Dopamine belongs to the family of catecholamines. It is a neurotransmitter.
● Hormones, Epinephrine and Norepinephrine (other catecholamines) are derived from Dopamine
● Dopamine plays a significant role in learning, goal-directed behavior, regulation of hormones, motor
control.
DOPAMINE SYNTHESIS
Phenylalanine (amino acid from diet) -> phenyalanine hydroxylase -> Tyrosine -> Tyrosine hydroxylase ->
DOPA -> Dopa decarboxylase -> Dopamine
KEY POINT: Dopamine is synthesized directly from tyrosine or indirectly from phenylalanine
● Dopamine is packed and stored into synaptic vesicles via the vesicular monoamine transporter (VMAT2)
and stored until its release into the synapse.
● When dopamine is released during neurotransmission, it acts on 5 types of postsynaptic receptors (D1-D5).
● A negative feedback mechanism exists through the presynaptic D2 receptor which regulates the release of
dopamine from the presynaptic neuron.
● Any excess dopamine is cleared out
o Presynaptically by Dopamine transporter (DAT)
o VMAT2 will take excess DA and store it in the synaptic vesicles for future neurotransmission
● Excess dopamine is broken down within the presynaptic neuron by monoamine oxidase A (MAO-A),
MAO-B and extracellularly (outside the neuron) by catechol-o methyltransferase (COMT).
● All antipsychotic drugs can reduce dopaminergic neurotransmission.
DOPAMINE RECEPTORS
● Dopamine neurotransmission is perpetuated via G protein-coupled receptors categorized into two broader
subtypes
● D1 – like family:
o Includes subtypes D1 and D5
o Activation is coupled to Gs ; activates adenylyl cylcase which leads to increase in concentration of
cAMP
● D2 – like family:
o Includes D2, D3 and D4
o Activation is coupled to Gi ; inhibits adenylyl cyclase leading to decrease in concentration of cAMP
o Also open K channels & closes Ca influx
● DAT (dopamine transporter) and VMAT2 are DA receptors that also regulate DA neurotransmission
● Presynaptic D2 autoreceptors are “gatekeepers” and provide negative feedback input. When D2 receptors are
NOT bound to DA DA release. When D2 receptors bind to DA inhibit DA release
o Location: Striatum, substantia nigra, pituitary
o Located presynaptic and postsynaptic
FGAs and Neurotransmitters
● Mesolimbic pathway: involved in pleasure and reward. Blocking D2 in this pathway by FGA’s not only
treats positive symptoms, but it blocks the reward mechanism and can cause apathy, lack of motivation, lack
of interest and the ability to feel joyful
● Negative symptoms of psychosis are due to low dopamine in the mesocortical pathway. When FGA’s block
D2 receptors here, negative symptoms such as blunted affect, lack of pleasure, reduced social interaction
can worse
● Dopamine inhibits prolactin release in the tuberoinfundibular pathway. When FGA’s bind to D2 in this
pathway, there is an increase in serum prolactin levels leading to galactorrhea, infertility or low sex drive.
, 2
● The degree of D2 receptor binding in the mesolimbic pathway needed for antipsychotic effects is close to
80% , while D2 receptor occupancy greater than 80% in the dorsal striatum is associated with EPS and in
the pituitary is associated with hyperprolactinemia. This creates a very narrow therapeutic window Between
the threshold for antipsychotic efficacy and that for side effects in terms of a D2 binding.
● If D2 receptors in the nigrostriatal DA pathway are blocked chronically, it can cause TD. D2 receptors are
hypothesized to become super sensitive or to upregulate (i.e.increase in number) perhaps in an attempt to
overcome drug induced blockade of D2 receptors in the striatum. After long term treatment the D2 receptors
apparently cannot or do not reset back to normal even when conventional antipsychotics are discontinued.
This leads to tardive dyskinesia that is irreversible, continuing whether conventional antipsychotic drugs are
administered or not
● In addition to binding to D2 in all pathways, FGA’s also block muscarinic M1 cholinergic receptors, leading
to blurry vision, dry mouth, constipation and cognitive blunting (Stahl, p.138). FGAs that caused more EPS
are the agents that have weak anti cholinergic properties, whereas those FGAs that cause fewer EPS are the
agents that have stronger anti cholinergic properties. Dopamine normally inhibits acetylcholine. If dopamine
can no longer suppress acetylcholine release then acetylcholine becomes overly active. Therefore, EPS is a
result of dopamine deficiency and excess acetylcholine. Drugs with anticholinergic actions will diminish the
excess acetylcholine activity caused by removal of dopamine inhibition when dopamine receptors are
blocked by FGAs. Thus, EPS is reduced. This occurs in the nigrostriatal dopamine pathway.
● The use of anticholinergic drugs with an FGA does not lessen the ability of the FGA to cause tardive
dyskinesia.
● Other properties of FGA’s is the blockade of histamine receptors which leads to weight gain and drowsiness
(Stahl, 2013). Blockade of alpha1 receptors can have cardiovascular effects, such as hypotension and
drowsiness.
● An old-fashioned way to sub classify FGAs is low potency versus high potency. Low potency agents tend to
have more of the additional properties such as blockade of muscarinic M1-cholinergic receptor, blockade of
histamine and alpha1-adrenergic receptors.
SEROTONIN SYNTHESIS AND TERMINATION OF ACTION
● Serotonin also known as 5- hydroxytryptamine (5HT) is produced from enzymes after the amino acid
precursor tryptophan is transported into the serotonin neuron. Tryptophan is converted by the enzyme
tryptophan hydroxylase (TRY-OH) into 5-hydroxytryptophan, which is then converted into 5HT by the
enzyme, aromatic amino acid decarboxylase (AAADC).
● Serotonin is then taken up into synaptic vesicles via the vesicular monoamine transporter (VMAT2), where
it stays until released by a neuron impulse. The 5HT neuron also has a presynaptic transport pump for
serotonin called the serotonin transporter (SERT) that terminates serotonin's actions by pumping it out of the
synapse and back into the presynaptic nerve terminal where it can be restored in synaptic vesicles for
subsequent use.
SGAs and Neurotransmitters
● Second generation antipsychotics are a class defined as serotonin- dopamine antagonists. They have an
affinity of blocking serotonin and D2 receptors. SGA's almost always have higher affinity for 5HT2A
receptors than they do for D2 receptors (p.154).
o Other actions include partial agonism at 5HT1A receptors and partial agonist at D2 receptors.
● SGA’s are different in that they bind to both D2 and serotonin receptors in the nigrostriatal pathway.
● Therapeutic window: The 5HT2A and 5HT1A properties of SGA's lower the amount of D2 blockade in the
dorsal striatum (nigrostriatal) and in the pituitary to 60%. D2 receptor occupancy remains to be up to 80% in
the limbic area (nucleus accumbens).
● 5HT2A stimulation of cortical pyramidal neurons normally block downstream dopamine release in the
striatum. It does this via stimulation of glutamate release in the brainstem that triggers release of inhibitory
, 3
GABA there. GABA binds to dopamine neurons projecting from the substantia nigra to the striatum, which
inhibits dopamine release.
● 5HT2A antagonism increases dopamine in the cortex (nigrostriatal pathway), which results in less EPS.
5HT2A antagonism in the cortex stimulates downstream dopamine release in the striatum. It does this by
reducing glutamate release in the brainstem, which in turn fails to trigger the release of inhibitory GABA.
Results, in the release of dopamine in the striatum, because GABA cannot inhibit dopamine release from the
substantia nigra into the striatum.
● 5HT2A antagonism decreases negative symptoms by increasing DA in the mesocortical (prefrontal cortex)
pathway, and antidepressant effects by increasing DA.
● 5HT2A antagonism decreases risk of hyperprolactinemia in the tuberoinfundibular pathway. Dopamine
inhibits prolactin release via stimulating D2 receptors, whereas serotonin promotes prolactin release via
stimulating 5 HT2A receptors. simultaneous inhibition of 5HT2A receptors in D2 receptors mean the risk of
prolactin release is low. Essentially, they cancel out each other (Reciprocal regulatory action).
● In the mesolimbic pathway, SGA's have equal efficacy as FGA's, due to regional differences in the way in
which 5HT2A receptors can or cannot exert control over dopamine release.
Bind more potently to 5HT2A than Bind more potently to D2 Bind equally at 5HT2A and D2
D2 than 5HT2A
The “pines” “Two pips and a rip” “Two pips and a rip”
-clozapine, olanzapine, quetiapine, -aripiprazole -brexiprazole
asenapine -cariprazine
The “dones”
-risperidone, paliperidone,
ziprasidone, ilioperidone, lurasidone
Bind more potently to 5HT1A than Bind more potently to D2 Bind equally at 5HT1A and D2
D2 and 5HT1A partial agonists
-clozapine, quetiapine -asenapine -aripiprazole
- all of the “dones” -cariprazine
1. Olanzapine does not bind to 5HT1A
2. Brexiprazole: 5HT1A binding is its most potent property
Presynaptic 5HT1A receptors in raphe and postsynaptic 5HT1A receptors in the PFC stimulation
increases dopamine release. Serotonin binding to 5HT1A receptors in the raphe nucleus inhibits serotonin
release. In the striatum, reduced serotonin means that 5HT2A receptors on GABA and dopamine neurons are
not stimulated. This means dopamine release is NOT inhibited. This causes dopamine release in the striatum,
and mitigates EPS.
5HT1B/D receptors: Detected in the synapse by presynaptic 5HT receptors on axon terminals, occurs via
5HT1B/D receptors, also known as a terminal autoreceptor. Drugs that block this receptor can promote 5HT
release and could hypothetically result in antidepressant actions.
5HT2c receptors: Postsynaptic, regulate dopamine and norepinephrine release. Stimulating this receptor
suppresses dopamine release more so in the mesolimbic than in the nigrostriatal pathways, which results in an
antipsychotic without EPS. Example – vabacaserin. Agonism of this receptor is also an experimental approach
to the treatment of obesity. Psychopharmacological treatments for obesity, include lorcaserin.
-Antagonism of serotonin 2C receptors is associated with increased risk for weight gain, perhaps due to
stimulation of appetite regulated by the hypothalamus
NSG552 / NSG 552 EXAM 1
STUDY GUIDE + REVIEW
Psychopharmacology - Wilkes
100% Guarantee Pass
This PDF contains:
NSG 552 EXAM 1 STUDY GUIDE
NSG 552 EXAM 1 REVIEW
Everything in Here to Pass the Exam 1
Expert-Verified
, 1
DOPAMINE
● Dopamine belongs to the family of catecholamines. It is a neurotransmitter.
● Hormones, Epinephrine and Norepinephrine (other catecholamines) are derived from Dopamine
● Dopamine plays a significant role in learning, goal-directed behavior, regulation of hormones, motor
control.
DOPAMINE SYNTHESIS
Phenylalanine (amino acid from diet) -> phenyalanine hydroxylase -> Tyrosine -> Tyrosine hydroxylase ->
DOPA -> Dopa decarboxylase -> Dopamine
KEY POINT: Dopamine is synthesized directly from tyrosine or indirectly from phenylalanine
● Dopamine is packed and stored into synaptic vesicles via the vesicular monoamine transporter (VMAT2)
and stored until its release into the synapse.
● When dopamine is released during neurotransmission, it acts on 5 types of postsynaptic receptors (D1-D5).
● A negative feedback mechanism exists through the presynaptic D2 receptor which regulates the release of
dopamine from the presynaptic neuron.
● Any excess dopamine is cleared out
o Presynaptically by Dopamine transporter (DAT)
o VMAT2 will take excess DA and store it in the synaptic vesicles for future neurotransmission
● Excess dopamine is broken down within the presynaptic neuron by monoamine oxidase A (MAO-A),
MAO-B and extracellularly (outside the neuron) by catechol-o methyltransferase (COMT).
● All antipsychotic drugs can reduce dopaminergic neurotransmission.
DOPAMINE RECEPTORS
● Dopamine neurotransmission is perpetuated via G protein-coupled receptors categorized into two broader
subtypes
● D1 – like family:
o Includes subtypes D1 and D5
o Activation is coupled to Gs ; activates adenylyl cylcase which leads to increase in concentration of
cAMP
● D2 – like family:
o Includes D2, D3 and D4
o Activation is coupled to Gi ; inhibits adenylyl cyclase leading to decrease in concentration of cAMP
o Also open K channels & closes Ca influx
● DAT (dopamine transporter) and VMAT2 are DA receptors that also regulate DA neurotransmission
● Presynaptic D2 autoreceptors are “gatekeepers” and provide negative feedback input. When D2 receptors are
NOT bound to DA DA release. When D2 receptors bind to DA inhibit DA release
o Location: Striatum, substantia nigra, pituitary
o Located presynaptic and postsynaptic
FGAs and Neurotransmitters
● Mesolimbic pathway: involved in pleasure and reward. Blocking D2 in this pathway by FGA’s not only
treats positive symptoms, but it blocks the reward mechanism and can cause apathy, lack of motivation, lack
of interest and the ability to feel joyful
● Negative symptoms of psychosis are due to low dopamine in the mesocortical pathway. When FGA’s block
D2 receptors here, negative symptoms such as blunted affect, lack of pleasure, reduced social interaction
can worse
● Dopamine inhibits prolactin release in the tuberoinfundibular pathway. When FGA’s bind to D2 in this
pathway, there is an increase in serum prolactin levels leading to galactorrhea, infertility or low sex drive.
, 2
● The degree of D2 receptor binding in the mesolimbic pathway needed for antipsychotic effects is close to
80% , while D2 receptor occupancy greater than 80% in the dorsal striatum is associated with EPS and in
the pituitary is associated with hyperprolactinemia. This creates a very narrow therapeutic window Between
the threshold for antipsychotic efficacy and that for side effects in terms of a D2 binding.
● If D2 receptors in the nigrostriatal DA pathway are blocked chronically, it can cause TD. D2 receptors are
hypothesized to become super sensitive or to upregulate (i.e.increase in number) perhaps in an attempt to
overcome drug induced blockade of D2 receptors in the striatum. After long term treatment the D2 receptors
apparently cannot or do not reset back to normal even when conventional antipsychotics are discontinued.
This leads to tardive dyskinesia that is irreversible, continuing whether conventional antipsychotic drugs are
administered or not
● In addition to binding to D2 in all pathways, FGA’s also block muscarinic M1 cholinergic receptors, leading
to blurry vision, dry mouth, constipation and cognitive blunting (Stahl, p.138). FGAs that caused more EPS
are the agents that have weak anti cholinergic properties, whereas those FGAs that cause fewer EPS are the
agents that have stronger anti cholinergic properties. Dopamine normally inhibits acetylcholine. If dopamine
can no longer suppress acetylcholine release then acetylcholine becomes overly active. Therefore, EPS is a
result of dopamine deficiency and excess acetylcholine. Drugs with anticholinergic actions will diminish the
excess acetylcholine activity caused by removal of dopamine inhibition when dopamine receptors are
blocked by FGAs. Thus, EPS is reduced. This occurs in the nigrostriatal dopamine pathway.
● The use of anticholinergic drugs with an FGA does not lessen the ability of the FGA to cause tardive
dyskinesia.
● Other properties of FGA’s is the blockade of histamine receptors which leads to weight gain and drowsiness
(Stahl, 2013). Blockade of alpha1 receptors can have cardiovascular effects, such as hypotension and
drowsiness.
● An old-fashioned way to sub classify FGAs is low potency versus high potency. Low potency agents tend to
have more of the additional properties such as blockade of muscarinic M1-cholinergic receptor, blockade of
histamine and alpha1-adrenergic receptors.
SEROTONIN SYNTHESIS AND TERMINATION OF ACTION
● Serotonin also known as 5- hydroxytryptamine (5HT) is produced from enzymes after the amino acid
precursor tryptophan is transported into the serotonin neuron. Tryptophan is converted by the enzyme
tryptophan hydroxylase (TRY-OH) into 5-hydroxytryptophan, which is then converted into 5HT by the
enzyme, aromatic amino acid decarboxylase (AAADC).
● Serotonin is then taken up into synaptic vesicles via the vesicular monoamine transporter (VMAT2), where
it stays until released by a neuron impulse. The 5HT neuron also has a presynaptic transport pump for
serotonin called the serotonin transporter (SERT) that terminates serotonin's actions by pumping it out of the
synapse and back into the presynaptic nerve terminal where it can be restored in synaptic vesicles for
subsequent use.
SGAs and Neurotransmitters
● Second generation antipsychotics are a class defined as serotonin- dopamine antagonists. They have an
affinity of blocking serotonin and D2 receptors. SGA's almost always have higher affinity for 5HT2A
receptors than they do for D2 receptors (p.154).
o Other actions include partial agonism at 5HT1A receptors and partial agonist at D2 receptors.
● SGA’s are different in that they bind to both D2 and serotonin receptors in the nigrostriatal pathway.
● Therapeutic window: The 5HT2A and 5HT1A properties of SGA's lower the amount of D2 blockade in the
dorsal striatum (nigrostriatal) and in the pituitary to 60%. D2 receptor occupancy remains to be up to 80% in
the limbic area (nucleus accumbens).
● 5HT2A stimulation of cortical pyramidal neurons normally block downstream dopamine release in the
striatum. It does this via stimulation of glutamate release in the brainstem that triggers release of inhibitory
, 3
GABA there. GABA binds to dopamine neurons projecting from the substantia nigra to the striatum, which
inhibits dopamine release.
● 5HT2A antagonism increases dopamine in the cortex (nigrostriatal pathway), which results in less EPS.
5HT2A antagonism in the cortex stimulates downstream dopamine release in the striatum. It does this by
reducing glutamate release in the brainstem, which in turn fails to trigger the release of inhibitory GABA.
Results, in the release of dopamine in the striatum, because GABA cannot inhibit dopamine release from the
substantia nigra into the striatum.
● 5HT2A antagonism decreases negative symptoms by increasing DA in the mesocortical (prefrontal cortex)
pathway, and antidepressant effects by increasing DA.
● 5HT2A antagonism decreases risk of hyperprolactinemia in the tuberoinfundibular pathway. Dopamine
inhibits prolactin release via stimulating D2 receptors, whereas serotonin promotes prolactin release via
stimulating 5 HT2A receptors. simultaneous inhibition of 5HT2A receptors in D2 receptors mean the risk of
prolactin release is low. Essentially, they cancel out each other (Reciprocal regulatory action).
● In the mesolimbic pathway, SGA's have equal efficacy as FGA's, due to regional differences in the way in
which 5HT2A receptors can or cannot exert control over dopamine release.
Bind more potently to 5HT2A than Bind more potently to D2 Bind equally at 5HT2A and D2
D2 than 5HT2A
The “pines” “Two pips and a rip” “Two pips and a rip”
-clozapine, olanzapine, quetiapine, -aripiprazole -brexiprazole
asenapine -cariprazine
The “dones”
-risperidone, paliperidone,
ziprasidone, ilioperidone, lurasidone
Bind more potently to 5HT1A than Bind more potently to D2 Bind equally at 5HT1A and D2
D2 and 5HT1A partial agonists
-clozapine, quetiapine -asenapine -aripiprazole
- all of the “dones” -cariprazine
1. Olanzapine does not bind to 5HT1A
2. Brexiprazole: 5HT1A binding is its most potent property
Presynaptic 5HT1A receptors in raphe and postsynaptic 5HT1A receptors in the PFC stimulation
increases dopamine release. Serotonin binding to 5HT1A receptors in the raphe nucleus inhibits serotonin
release. In the striatum, reduced serotonin means that 5HT2A receptors on GABA and dopamine neurons are
not stimulated. This means dopamine release is NOT inhibited. This causes dopamine release in the striatum,
and mitigates EPS.
5HT1B/D receptors: Detected in the synapse by presynaptic 5HT receptors on axon terminals, occurs via
5HT1B/D receptors, also known as a terminal autoreceptor. Drugs that block this receptor can promote 5HT
release and could hypothetically result in antidepressant actions.
5HT2c receptors: Postsynaptic, regulate dopamine and norepinephrine release. Stimulating this receptor
suppresses dopamine release more so in the mesolimbic than in the nigrostriatal pathways, which results in an
antipsychotic without EPS. Example – vabacaserin. Agonism of this receptor is also an experimental approach
to the treatment of obesity. Psychopharmacological treatments for obesity, include lorcaserin.
-Antagonism of serotonin 2C receptors is associated with increased risk for weight gain, perhaps due to
stimulation of appetite regulated by the hypothalamus
