Executive Solution Overview
follow the sample and rubric **files (4)** – ## Module_5_Weekly_Note_Outline-note.docx – ## Week5Notes-RUBRIC.pdf – ## WEEKLY_NOT_SAMPLE.docx – Stahl_Chapter_5_159-244.pdf **## Module_5_Weekly_Note_Outline-note.docx** **Chapter 5 Outline** **Read** Chapter 5, pages 159- 244. **No refere…
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follow the sample and rubric
**files (4)**
– ## Module_5_Weekly_Note_Outline-note.docx
– ## Week5Notes-RUBRIC.pdf
– ## WEEKLY_NOT_SAMPLE.docx
– Stahl_Chapter_5_159-244.pdf
**## Module_5_Weekly_Note_Outline-note.docx**
**Chapter 5 Outline**
**Read** Chapter 5, pages 159- 244.
**No reference needed.**
**Targeting Dopamine and Serotonin Receptors for Psychosis, Mood, and Beyond: So-Called “Antipsychotics”**
Module 5 Weekly Note. Address each heading in the yellow outline note.
Targeting Mesolimbic/Mesostriatal Dopamine D2 Receptors Causes Antipsychotic Actions 161
Targeting Dopamine D2 Receptors in Mesolimbic/ Mesostriatal and Mesocortical Pathways Causes Secondary Negative Symptoms 162
Secondary Negative Symptoms Due to Targeting Mesolimbic Dopamine D2 Receptors 162
Secondary Negative Symptoms Due to Targeting Mesocortical Dopamine D2 Receptors 163
Targeting Tuberoinfundibular Dopamine D2 Receptors Causes Elevation of Prolactin 164
Targeting Nigrostriatal Dopamine D2 Receptors Causes Motor Side Effects 165
Drug-Induced Parkinsonism 166
Drug-Induced Acute Dystonia 169
Akathisia 169
Neuroleptic Malignant Syndrome 169
Tardive Dyskinesia 170
Drugs Targeting Dopamine D2 Receptors: So-Called First Generation or Conventional “Antipsychotics” 179
Drugs Targeting Serotonin 2A Receptors with or without Simultaneously Targeting Dopamine D2 Receptors 183
5HT2A Receptor Regulation of Dopamine Release in Three Downstream Pathways 184
Drugs Targeting Serotonin 1A Receptors and Dopamine D2 Receptors as Partial Agonists 189
D2 Partial Agonism 189
How Does D2 Partial Agonism Cause Fewer Motor Side Effects than D2 Antagonism? 192
5HT1A Partial Agonism 193
Links between Receptor Binding Properties of Drugs Used to Treat Psychosis and Other Therapeutic Actions and Side Effects 195
Mania 195
Antidepressant Actions in Bipolar and Unipolar Depression 195
Anxiolytic Actions 196
Agitation in Dementia 197
Sedative Hypnotic and Sedating Actions 197
Cardiometabolic Actions 198
Pharmacological Properties of Selected Individual First-Generation D2 Antagonists 201
Chlorpromazine 201
Fluphenazine 202
Haloperidol 202
Sulpiride 202
Amisulpride 203
An Overview of the Pharmacological Properties of Individual 5HT2A/ D2 Antagonists and D2/5HT1A Partial Agonists: The Pines (Peens), Many Dones and a Rone, Two Pips and a Rip 204
The Pines (Peens) 222
Many Dones and a Rone 234
Two Pips and a Rip 239
Selective 5HT2A Antagonist 240
The Others 240
Future Treatments for Schizophrenia 241
Roluperidone (MIN-101) 241
D3 Antagonists 241
Trace Amine Receptor Agonists and SEP- 363856 241
Cholinergic Agonists 242
A Few Other Ideas 242
Summary 242
## image1.png
**## Week5Notes-RUBRIC.pdf**
Weekly Notes Rubric (1)
9/26/26, 8:49 AM Week 5 Notes
https://dyc.instructure.com/courses/52441/assignments/452952?module_item_id=1196142 1/3
Criteria Ratings Pts
Content
5 pts
Organization
5 pts
Clarity
5 pts
Relevance
5 pts
Critical
Thinking
5 pts
5 to >4.0 pts
Excellent
Comprehensive
coverage of key
concepts, details, and
examples.
4 to >3.0 pts
Good
Thorough coverage of
most key concepts
and details.
3 to >2.0 pts
Fair
Adequate coverage of
basic concepts
2 to >1.0 pts
Needs Improvement
Incomplete coverage,
missing important
concepts.
1 to >0 pts
No Credit
5 to >4.0 pts
Excellent
Well-structured and
logically organized.
Subheadings reflect
reading assignment
4 to >3.0 pts
Good
Clear organization with
headings or
formatting.
3 to >2.0 pts
Fair
Somewhat organized
with inconsistencies.
Some heading noted
2 to >1.0 pts
Needs Improvement
Disorganized, difficult
to follow, little to no
headings
1 to >0 pts
No Credit
5 to >4.0 pts
Full Marks
Very clear and concise
language
4 to >3.0 pts
Good
Clear language with
few confusing parts.
3 to >2.0 pts
Fair
Mostly clear, some
parts confusing.
2 pts
Needs Improvement
Unclear and
convoluted language.
2 to >0 pts
No Credit
5 to >4.0 pts
Excellent
Directly addresses
main themes and
concepts.
4 to >3.0 pts
Good
Focused on main
themes, minimal
irrelevant info.
3 to >2.0 pts
Fair
Relevant info with
tangential details.
2 to >1.0 pts
Needs Improvement
Includes irrelevant
details.
1 to >0 pts
No Credit
5 to >4.0 pts
Excellent
Insightful connections
between concepts.
4 to >3.0 pts
Good
Demonstrates
understanding, some
connections.
3 to >2.0 pts
Fair
Basic understanding,
limited connections.
2 to >1.0 pts
Needs Improvement
Unclear
understanding, lacks
connections
1 to >0 pts
No Credit
9/26/26, 8:49 AM Week 5 Notes
https://dyc.instructure.com/courses/52441/assignments/452952?module_item_id=1196142 2/3
Criteria Ratings Pts
Neatness
and Format
5 pts
Overall
Quality
5 pts
Total Points: 35
5 to >4.0 pts
Excellent
Neat and visually
appealing with proper
formatting. *If
handwritten, clear and
legible writing, with
appropriate spacing
4 to >3.0 pts
Good
Neat and organized,
effective formatting.
Minor formatting and
unorganized errors.
3 to >2.0 pts
Fair
Mostly neat,
inconsistent
formatting.
2 to >1.0 pts
Needs Improvement
Messy Unorganized,
lacks formatting.
1 to >0 pts
No Credit
5 to >4.0 pts
Excellent
Exceptional quality
with deep
understanding.
4 to >3.0 pts
Good
Good quality, clear
understanding.
3 to >2.0 pts
Fair
Adequate quality,
needs improvement in
areas mentioned
above
2 to >1.0 pts
Needs Improvement
Significantly deficient
quality
1 to >0 pts
No Credit
9/26/26, 8:49 AM Week 5 Notes
https://dyc.instructure.com/courses/52441/assignments/452952?module_item_id=1196142 3/3
**## WEEKLY_NOT_SAMPLE.docx**
1
**4**
**Weekly Notes – Chapter 2: Module 2**
**Transporters, Receptors, and Enzymes as Targets of Psychopharmacological Drug Action**
**Neurotransmitter Transporters as Targets of Drug Action.**
Transporters control the transport of a neurotransmitter into and out of a neuron. They control the reuptake of neurotransmitters, which is the amount of time they spend in the synapse and thus affects communication between two neurons.
**Classification and Structure – p. 29**
Some of the neurotransmitter transporters have several transmembrane domains and are members of the SLC family. Their structure enables them to recognize specific chemical substances and transport them across the nerve cell membrane.
These transporters in general have 12 transmembrane regions. Plasma-membrane transporters include the SLC6 and SLC1 gene families.
**Monoamine Transporters (SLC6 Gene Family)– p. 31**
**Major Monoamine Transporters**
SERT = serotonin transporter
NET = norepinephrine transporter
DAT = dopamine transporter
Serotonin, norepinephrine, and dopamine transporters are members of the SLC6 family. Inhibitory drugs of these transporters may lead to higher levels of neurotransmitters in the synaptic cleft, which has significant therapeutic effects in psychiatric conditions.
**Other Neurotransmitter Transporters (SLC6 and SLC1 Gene Families)– p. 34**
**GABA and Glutamate**
GABA: There are several GABA transporters called GAT1–4.
Glutamate: Glutamate transporters are called EAAT1–5 and belong to the SLC1 family.
Other transporters control the levels of neurotransmitters such as GABA, glycine, and glutamate. Modifying these systems can also modify inhibitory or excitatory signaling and can have an impact on neurological and psychiatric symptoms.
**Histamine and Neuropeptide Transporters– p. 35**
Unlike monoamines, histamine and neuropeptides lack a presynaptic reuptake system. Their activity is regulated in other ways, such as being broken down by enzymes and diffused out of the cell.
**Vesicular Transporters: Subtypes and Function.– p. 35**
Neurotransmitters are taken into vesicles for release by vesicular transporters. They help to accumulate neurotransmitters within vesicles, ready for movement to the nerve cell for communication.
VMAT2 → serotonin, norepinephrine, dopamine, histamine
VAChT → acetylcholine
VIAAT → GABA
vGluT1–3 → glutamate
**Vesicular Transporters as Drug Targets– p. 35**
VMAT2 and other vesicular proteins can be influenced by psychotropic medications and stimulant drugs. Altered vesicular storage can significantly affect neurotransmitter release.
**G-Protein-Linked Receptors– p. 36**
These receptors have 7 membrane-spanning regions and convert binding of neurotransmitters into intracellular signals. The effects can be seen in the immediate receptor, but can also be seen in second messengers, proteins, and gene expression.
**Structure and Function**
The activity of receptors is not binary, but lies on a continuum from full activation to decreased activation. Agonists activate receptors; antagonists are molecules that don't activate receptors; partial agonists activate receptors, albeit not as strongly as full agonists; and inverse agonists decrease constitutive activity.
**G-Protein-Linked Receptors as Targets of Psychotropic Drugs– p. 36**
Several receptor types interact with psychotropic medications, including dopamine, serotonin, histamine, GABA, adrenergic, and melatonin receptors. The clinical effects of drugs vary depending on whether they stimulate, block, or stabilize receptor activity.
**The Agonist Spectrum**
Full agonist → Partial agonist → Antagonist → Inverse agonist
Full agonist: Creates maximum receptor activation and signal transduction.
Antagonist: Blocks agonist activity but does not independently activate the receptor. True antagonists are described as "silent".
Partial Agonist: Produces more activity than an antagonist; however, it has less activity than a full agonist.
_Partial agonists can function as stabilizers. When neurotransmitter activity is low, it increases activity; when full-agonist activity is high, it reduces activity to an intermediate level._
Light/rheostat analogy:
Full agonist = brightest light
Partial agonist = dimmed light but still shining
No agonist = light off
Inverse Agonist: Reduces receptor activity below baseline constitutive activity. Inverse agonists are above simple antagonists and are neither neutral nor silent. It produces a conformational transformation in the G-protein-linked receptor that stabilizes the inactive form.
Full agonist: ↑↑↑ activity
Partial agonist: ↑ activity
Antagonist: baseline
Inverse agonist: ↓ below baseline
**Enzymes as Sites of Psychopharmacological Drug Action -p. 45**
Enzymes are yet another pharmaceutical target. The effects of drugs can alter the synthesis and degradation mechanisms of neurotransmitters or alter how they are used in the cell, which can change the function of the neurons.
Enzymes convert a substrate into a product.
Substrate → binds active site → enzyme modifies substrate → product
Irreversible Inhibitor: Binds permanently to the enzyme and cannot be displaced by the substrate. Enzyme activity returns only after the cell synthesizes new enzyme molecules. Sometimes it is called a "suicide inhibitor." It is called this because it permanently inhibits the enzyme and therefore kills it.
Reversible Inhibitor: Can be displaced by the enzyme's substrate because it is able to compete with it. Whether the inhibitor or substrate predominates depends on factors such as relative affinity and concentration.
Important enzymes targeted by psychotropic drugs include:
MAO – monoamine oxidase
Acetylcholinesterase
GSK – glycogen synthase kinase
Lithium may inhibit GSK-3, potentially contributing to neuroprotective effects, long-term plasticity, and its antimanic/mood-stabilizing actions
**Cytochrome P450 Drug-Metabolizing Enzymes As Targets Of Psychotropic Drugs-p. 49**
CYP450 enzymes are mainly responsible for how medicines are metabolized in the body. Enzyme activity can vary, affecting drug concentration, efficacy, and the risk of adverse effects in treating psychological disorders, making metabolism a critical factor.
**Pharmacokinetics vs. Pharmacodynamics**
The CYP450 system is found primarily in the liver and gut and is important for drug metabolism.
Pharmacokinetics = what the body does to the drug:
A – Absorption
D – Distribution
M – Metabolism
E – Excretion
Pharmacodynamics = what the drug does to the body, including its mechanism of action, therapeutic effects, and adverse effects.
Important CYP450 enzymes listed.
CYP1A2, CYP2B6, CYP2D6, CYP2C9, CYP2C19, CYP3A4
Poor/intermediate metabolizer: ↓ metabolism → potentially ↑ drug concentrations and adverse effects.
Ultra-rapid metabolizer: ↑ metabolism → potentially ↓ drug concentrations and reduced effectiveness.
Pharmacogenomic testing and therapeutic drug monitoring can sometimes help guide treatment, particularly in treatment-resistant patients.
**Summary -p. 50**
Transporters regulate neurotransmitter movement, receptors convert the chemical signal into a cellular response, and enzymes regulate biochemical processes. Drugs that affect the brain's chemistry, or signaling systems, are called psychotropic drugs, and they are used to achieve therapeutic effects.
_Source: Stahl's Essential Psychopharmacology, Chapter 2, pp. 29–50._
**Stahl_Chapter_5_159-244.pdf**
This file is too large to display. [View in new window](https://www.sweetstudy.com/files/stahl-chapter-5-159-244-pdf)
**Stahl_Chapter_5_159-244.pdf**
This file is too large to display. [View in new window](https://www.sweetstudy.com/files/stahl-chapter-5-159-244-pdf)
**## Module_5_Weekly_Note_Outline-note.docx**
**Chapter 5 Outline**
**Read** Chapter 5, pages 159- 244.
**No reference needed.**
**Targeting Dopamine and Serotonin Receptors for Psychosis, Mood, and Beyond: So-Called “Antipsychotics”**
Module 5 Weekly Note. Address each heading in the yellow outline note.
Targeting Mesolimbic/Mesostriatal Dopamine D2 Receptors Causes Antipsychotic Actions 161
Targeting Dopamine D2 Receptors in Mesolimbic/ Mesostriatal and Mesocortical Pathways Causes Secondary Negative Symptoms 162
Secondary Negative Symptoms Due to Targeting Mesolimbic Dopamine D2 Receptors 162
Secondary Negative Symptoms Due to Targeting Mesocortical Dopamine D2 Receptors 163
Targeting Tuberoinfundibular Dopamine D2 Receptors Causes Elevation of Prolactin 164
Targeting Nigrostriatal Dopamine D2 Receptors Causes Motor Side Effects 165
Drug-Induced Parkinsonism 166
Drug-Induced Acute Dystonia 169
Akathisia 169
Neuroleptic Malignant Syndrome 169
Tardive Dyskinesia 170
Drugs Targeting Dopamine D2 Receptors: So-Called First Generation or Conventional “Antipsychotics” 179
Drugs Targeting Serotonin 2A Receptors with or without Simultaneously Targeting Dopamine D2 Receptors 183
5HT2A Receptor Regulation of Dopamine Release in Three Downstream Pathways 184
Drugs Targeting Serotonin 1A Receptors and Dopamine D2 Receptors as Partial Agonists 189
D2 Partial Agonism 189
How Does D2 Partial Agonism Cause Fewer Motor Side Effects than D2 Antagonism? 192
5HT1A Partial Agonism 193
Links between Receptor Binding Properties of Drugs Used to Treat Psychosis and Other Therapeutic Actions and Side Effects 195
Mania 195
Antidepressant Actions in Bipolar and Unipolar Depression 195
Anxiolytic Actions 196
Agitation in Dementia 197
Sedative Hypnotic and Sedating Actions 197
Cardiometabolic Actions 198
Pharmacological Properties of Selected Individual First-Generation D2 Antagonists 201
Chlorpromazine 201
Fluphenazine 202
Haloperidol 202
Sulpiride 202
Amisulpride 203
An Overview of the Pharmacological Properties of Individual 5HT2A/ D2 Antagonists and D2/5HT1A Partial Agonists: The Pines (Peens), Many Dones and a Rone, Two Pips and a Rip 204
The Pines (Peens) 222
Many Dones and a Rone 234
Two Pips and a Rip 239
Selective 5HT2A Antagonist 240
The Others 240
Future Treatments for Schizophrenia 241
Roluperidone (MIN-101) 241
D3 Antagonists 241
Trace Amine Receptor Agonists and SEP- 363856 241
Cholinergic Agonists 242
A Few Other Ideas 242
Summary 242
## image1.png
**## Week5Notes-RUBRIC.pdf**
Weekly Notes Rubric (1)
9/26/26, 8:49 AM Week 5 Notes
https://dyc.instructure.com/courses/52441/assignments/452952?module_item_id=1196142 1/3
Criteria Ratings Pts
Content
5 pts
Organization
5 pts
Clarity
5 pts
Relevance
5 pts
Critical
Thinking
5 pts
5 to >4.0 pts
Excellent
Comprehensive
coverage of key
concepts, details, and
examples.
4 to >3.0 pts
Good
Thorough coverage of
most key concepts
and details.
3 to >2.0 pts
Fair
Adequate coverage of
basic concepts
2 to >1.0 pts
Needs Improvement
Incomplete coverage,
missing important
concepts.
1 to >0 pts
No Credit
5 to >4.0 pts
Excellent
Well-structured and
logically organized.
Subheadings reflect
reading assignment
4 to >3.0 pts
Good
Clear organization with
headings or
formatting.
3 to >2.0 pts
Fair
Somewhat organized
with inconsistencies.
Some heading noted
2 to >1.0 pts
Needs Improvement
Disorganized, difficult
to follow, little to no
headings
1 to >0 pts
No Credit
5 to >4.0 pts
Full Marks
Very clear and concise
language
4 to >3.0 pts
Good
Clear language with
few confusing parts.
3 to >2.0 pts
Fair
Mostly clear, some
parts confusing.
2 pts
Needs Improvement
Unclear and
convoluted language.
2 to >0 pts
No Credit
5 to >4.0 pts
Excellent
Directly addresses
main themes and
concepts.
4 to >3.0 pts
Good
Focused on main
themes, minimal
irrelevant info.
3 to >2.0 pts
Fair
Relevant info with
tangential details.
2 to >1.0 pts
Needs Improvement
Includes irrelevant
details.
1 to >0 pts
No Credit
5 to >4.0 pts
Excellent
Insightful connections
between concepts.
4 to >3.0 pts
Good
Demonstrates
understanding, some
connections.
3 to >2.0 pts
Fair
Basic understanding,
limited connections.
2 to >1.0 pts
Needs Improvement
Unclear
understanding, lacks
connections
1 to >0 pts
No Credit
9/26/26, 8:49 AM Week 5 Notes
https://dyc.instructure.com/courses/52441/assignments/452952?module_item_id=1196142 2/3
Criteria Ratings Pts
Neatness
and Format
5 pts
Overall
Quality
5 pts
Total Points: 35
5 to >4.0 pts
Excellent
Neat and visually
appealing with proper
formatting. *If
handwritten, clear and
legible writing, with
appropriate spacing
4 to >3.0 pts
Good
Neat and organized,
effective formatting.
Minor formatting and
unorganized errors.
3 to >2.0 pts
Fair
Mostly neat,
inconsistent
formatting.
2 to >1.0 pts
Needs Improvement
Messy Unorganized,
lacks formatting.
1 to >0 pts
No Credit
5 to >4.0 pts
Excellent
Exceptional quality
with deep
understanding.
4 to >3.0 pts
Good
Good quality, clear
understanding.
3 to >2.0 pts
Fair
Adequate quality,
needs improvement in
areas mentioned
above
2 to >1.0 pts
Needs Improvement
Significantly deficient
quality
1 to >0 pts
No Credit
9/26/26, 8:49 AM Week 5 Notes
https://dyc.instructure.com/courses/52441/assignments/452952?module_item_id=1196142 3/3
**## WEEKLY_NOT_SAMPLE.docx**
1
**4**
**Weekly Notes – Chapter 2: Module 2**
**Transporters, Receptors, and Enzymes as Targets of Psychopharmacological Drug Action**
**Neurotransmitter Transporters as Targets of Drug Action.**
Transporters control the transport of a neurotransmitter into and out of a neuron. They control the reuptake of neurotransmitters, which is the amount of time they spend in the synapse and thus affects communication between two neurons.
**Classification and Structure – p. 29**
Some of the neurotransmitter transporters have several transmembrane domains and are members of the SLC family. Their structure enables them to recognize specific chemical substances and transport them across the nerve cell membrane.
These transporters in general have 12 transmembrane regions. Plasma-membrane transporters include the SLC6 and SLC1 gene families.
**Monoamine Transporters (SLC6 Gene Family)– p. 31**
**Major Monoamine Transporters**
SERT = serotonin transporter
NET = norepinephrine transporter
DAT = dopamine transporter
Serotonin, norepinephrine, and dopamine transporters are members of the SLC6 family. Inhibitory drugs of these transporters may lead to higher levels of neurotransmitters in the synaptic cleft, which has significant therapeutic effects in psychiatric conditions.
**Other Neurotransmitter Transporters (SLC6 and SLC1 Gene Families)– p. 34**
**GABA and Glutamate**
GABA: There are several GABA transporters called GAT1–4.
Glutamate: Glutamate transporters are called EAAT1–5 and belong to the SLC1 family.
Other transporters control the levels of neurotransmitters such as GABA, glycine, and glutamate. Modifying these systems can also modify inhibitory or excitatory signaling and can have an impact on neurological and psychiatric symptoms.
**Histamine and Neuropeptide Transporters– p. 35**
Unlike monoamines, histamine and neuropeptides lack a presynaptic reuptake system. Their activity is regulated in other ways, such as being broken down by enzymes and diffused out of the cell.
**Vesicular Transporters: Subtypes and Function.– p. 35**
Neurotransmitters are taken into vesicles for release by vesicular transporters. They help to accumulate neurotransmitters within vesicles, ready for movement to the nerve cell for communication.
VMAT2 → serotonin, norepinephrine, dopamine, histamine
VAChT → acetylcholine
VIAAT → GABA
vGluT1–3 → glutamate
**Vesicular Transporters as Drug Targets– p. 35**
VMAT2 and other vesicular proteins can be influenced by psychotropic medications and stimulant drugs. Altered vesicular storage can significantly affect neurotransmitter release.
**G-Protein-Linked Receptors– p. 36**
These receptors have 7 membrane-spanning regions and convert binding of neurotransmitters into intracellular signals. The effects can be seen in the immediate receptor, but can also be seen in second messengers, proteins, and gene expression.
**Structure and Function**
The activity of receptors is not binary, but lies on a continuum from full activation to decreased activation. Agonists activate receptors; antagonists are molecules that don't activate receptors; partial agonists activate receptors, albeit not as strongly as full agonists; and inverse agonists decrease constitutive activity.
**G-Protein-Linked Receptors as Targets of Psychotropic Drugs– p. 36**
Several receptor types interact with psychotropic medications, including dopamine, serotonin, histamine, GABA, adrenergic, and melatonin receptors. The clinical effects of drugs vary depending on whether they stimulate, block, or stabilize receptor activity.
**The Agonist Spectrum**
Full agonist → Partial agonist → Antagonist → Inverse agonist
Full agonist: Creates maximum receptor activation and signal transduction.
Antagonist: Blocks agonist activity but does not independently activate the receptor. True antagonists are described as "silent".
Partial Agonist: Produces more activity than an antagonist; however, it has less activity than a full agonist.
_Partial agonists can function as stabilizers. When neurotransmitter activity is low, it increases activity; when full-agonist activity is high, it reduces activity to an intermediate level._
Light/rheostat analogy:
Full agonist = brightest light
Partial agonist = dimmed light but still shining
No agonist = light off
Inverse Agonist: Reduces receptor activity below baseline constitutive activity. Inverse agonists are above simple antagonists and are neither neutral nor silent. It produces a conformational transformation in the G-protein-linked receptor that stabilizes the inactive form.
Full agonist: ↑↑↑ activity
Partial agonist: ↑ activity
Antagonist: baseline
Inverse agonist: ↓ below baseline
**Enzymes as Sites of Psychopharmacological Drug Action -p. 45**
Enzymes are yet another pharmaceutical target. The effects of drugs can alter the synthesis and degradation mechanisms of neurotransmitters or alter how they are used in the cell, which can change the function of the neurons.
Enzymes convert a substrate into a product.
Substrate → binds active site → enzyme modifies substrate → product
Irreversible Inhibitor: Binds permanently to the enzyme and cannot be displaced by the substrate. Enzyme activity returns only after the cell synthesizes new enzyme molecules. Sometimes it is called a "suicide inhibitor." It is called this because it permanently inhibits the enzyme and therefore kills it.
Reversible Inhibitor: Can be displaced by the enzyme's substrate because it is able to compete with it. Whether the inhibitor or substrate predominates depends on factors such as relative affinity and concentration.
Important enzymes targeted by psychotropic drugs include:
MAO – monoamine oxidase
Acetylcholinesterase
GSK – glycogen synthase kinase
Lithium may inhibit GSK-3, potentially contributing to neuroprotective effects, long-term plasticity, and its antimanic/mood-stabilizing actions
**Cytochrome P450 Drug-Metabolizing Enzymes As Targets Of Psychotropic Drugs-p. 49**
CYP450 enzymes are mainly responsible for how medicines are metabolized in the body. Enzyme activity can vary, affecting drug concentration, efficacy, and the risk of adverse effects in treating psychological disorders, making metabolism a critical factor.
**Pharmacokinetics vs. Pharmacodynamics**
The CYP450 system is found primarily in the liver and gut and is important for drug metabolism.
Pharmacokinetics = what the body does to the drug:
A – Absorption
D – Distribution
M – Metabolism
E – Excretion
Pharmacodynamics = what the drug does to the body, including its mechanism of action, therapeutic effects, and adverse effects.
Important CYP450 enzymes listed.
CYP1A2, CYP2B6, CYP2D6, CYP2C9, CYP2C19, CYP3A4
Poor/intermediate metabolizer: ↓ metabolism → potentially ↑ drug concentrations and adverse effects.
Ultra-rapid metabolizer: ↑ metabolism → potentially ↓ drug concentrations and reduced effectiveness.
Pharmacogenomic testing and therapeutic drug monitoring can sometimes help guide treatment, particularly in treatment-resistant patients.
**Summary -p. 50**
Transporters regulate neurotransmitter movement, receptors convert the chemical signal into a cellular response, and enzymes regulate biochemical processes. Drugs that affect the brain's chemistry, or signaling systems, are called psychotropic drugs, and they are used to achieve therapeutic effects.
_Source: Stahl's Essential Psychopharmacology, Chapter 2, pp. 29–50._
**Stahl_Chapter_5_159-244.pdf**
This file is too large to display. [View in new window](https://www.sweetstudy.com/files/stahl-chapter-5-159-244-pdf)
**## Module_5_Weekly_Note_Outline-note.docx**
**Chapter 5 Outline**
**Read** Chapter 5, pages 159- 244.
**No reference needed.**
**Targeting Dopamine and Serotonin Receptors for Psychosis, Mood, and Beyond: So-Called “Antipsychotics”**
Module 5 Weekly Note. Address each heading in the yellow outline note.
Targeting Mesolimbic/Mesostriatal Dopamine D2 Receptors Causes Antipsychotic Actions 161
Targeting Dopamine D2 Receptors in Mesolimbic/ Mesostriatal and Mesocortical Pathways Causes Secondary Negative Symptoms 162
Secondary Negative Symptoms Due to Targeting Mesolimbic Dopamine D2 Receptors 162
Secondary Negative Symptoms Due to Targeting Mesocortical Dopamine D2 Receptors 163
Targeting Tuberoinfundibular Dopamine D2 Receptors Causes Elevation of Prolactin 164
Targeting Nigrostriatal Dopamine D2 Receptors Causes Motor Side Effects 165
Drug-Induced Parkinsonism 166
Drug-Induced Acute Dystonia 169
Akathisia 169
Neuroleptic Malignant Syndrome 169
Tardive Dyskinesia 170
Drugs Targeting Dopamine D2 Receptors: So-Called First Generation or Conventional “Antipsychotics” 179
Drugs Targeting Serotonin 2A Receptors with or without Simultaneously Targeting Dopamine D2 Receptors 183
5HT2A Receptor Regulation of Dopamine Release in Three Downstream Pathways 184
Drugs Targeting Serotonin 1A Receptors and Dopamine D2 Receptors as Partial Agonists 189
D2 Partial Agonism 189
How Does D2 Partial Agonism Cause Fewer Motor Side Effects than D2 Antagonism? 192
5HT1A Partial Agonism 193
Links between Receptor Binding Properties of Drugs Used to Treat Psychosis and Other Therapeutic Actions and Side Effects 195
Mania 195
Antidepressant Actions in Bipolar and Unipolar Depression 195
Anxiolytic Actions 196
Agitation in Dementia 197
Sedative Hypnotic and Sedating Actions 197
Cardiometabolic Actions 198
Pharmacological Properties of Selected Individual First-Generation D2 Antagonists 201
Chlorpromazine 201
Fluphenazine 202
Haloperidol 202
Sulpiride 202
Amisulpride 203
An Overview of the Pharmacological Properties of Individual 5HT2A/ D2 Antagonists and D2/5HT1A Partial Agonists: The Pines (Peens), Many Dones and a Rone, Two Pips and a Rip 204
The Pines (Peens) 222
Many Dones and a Rone 234
Two Pips and a Rip 239
Selective 5HT2A Antagonist 240
The Others 240
Future Treatments for Schizophrenia 241
Roluperidone (MIN-101) 241
D3 Antagonists 241
Trace Amine Receptor Agonists and SEP- 363856 241
Cholinergic Agonists 242
A Few Other Ideas 242
Summary 242
## image1.png
**## Week5Notes-RUBRIC.pdf**
Weekly Notes Rubric (1)
9/26/26, 8:49 AM Week 5 Notes
https://dyc.instructure.com/courses/52441/assignments/452952?module_item_id=1196142 1/3
Criteria Ratings Pts
Content
5 pts
Organization
5 pts
Clarity
5 pts
Relevance
5 pts
Critical
Thinking
5 pts
5 to >4.0 pts
Excellent
Comprehensive
coverage of key
concepts, details, and
examples.
4 to >3.0 pts
Good
Thorough coverage of
most key concepts
and details.
3 to >2.0 pts
Fair
Adequate coverage of
basic concepts
2 to >1.0 pts
Needs Improvement
Incomplete coverage,
missing important
concepts.
1 to >0 pts
No Credit
5 to >4.0 pts
Excellent
Well-structured and
logically organized.
Subheadings reflect
reading assignment
4 to >3.0 pts
Good
Clear organization with
headings or
formatting.
3 to >2.0 pts
Fair
Somewhat organized
with inconsistencies.
Some heading noted
2 to >1.0 pts
Needs Improvement
Disorganized, difficult
to follow, little to no
headings
1 to >0 pts
No Credit
5 to >4.0 pts
Full Marks
Very clear and concise
language
4 to >3.0 pts
Good
Clear language with
few confusing parts.
3 to >2.0 pts
Fair
Mostly clear, some
parts confusing.
2 pts
Needs Improvement
Unclear and
convoluted language.
2 to >0 pts
No Credit
5 to >4.0 pts
Excellent
Directly addresses
main themes and
concepts.
4 to >3.0 pts
Good
Focused on main
themes, minimal
irrelevant info.
3 to >2.0 pts
Fair
Relevant info with
tangential details.
2 to >1.0 pts
Needs Improvement
Includes irrelevant
details.
1 to >0 pts
No Credit
5 to >4.0 pts
Excellent
Insightful connections
between concepts.
4 to >3.0 pts
Good
Demonstrates
understanding, some
connections.
3 to >2.0 pts
Fair
Basic understanding,
limited connections.
2 to >1.0 pts
Needs Improvement
Unclear
understanding, lacks
connections
1 to >0 pts
No Credit
9/26/26, 8:49 AM Week 5 Notes
https://dyc.instructure.com/courses/52441/assignments/452952?module_item_id=1196142 2/3
Criteria Ratings Pts
Neatness
and Format
5 pts
Overall
Quality
5 pts
Total Points: 35
5 to >4.0 pts
Excellent
Neat and visually
appealing with proper
formatting. *If
handwritten, clear and
legible writing, with
appropriate spacing
4 to >3.0 pts
Good
Neat and organized,
effective formatting.
Minor formatting and
unorganized errors.
3 to >2.0 pts
Fair
Mostly neat,
inconsistent
formatting.
2 to >1.0 pts
Needs Improvement
Messy Unorganized,
lacks formatting.
1 to >0 pts
No Credit
5 to >4.0 pts
Excellent
Exceptional quality
with deep
understanding.
4 to >3.0 pts
Good
Good quality, clear
understanding.
3 to >2.0 pts
Fair
Adequate quality,
needs improvement in
areas mentioned
above
2 to >1.0 pts
Needs Improvement
Significantly deficient
quality
1 to >0 pts
No Credit
9/26/26, 8:49 AM Week 5 Notes
https://dyc.instructure.com/courses/52441/assignments/452952?module_item_id=1196142 3/3
**## WEEKLY_NOT_SAMPLE.docx**
1
**4**
**Weekly Notes – Chapter 2: Module 2**
**Transporters, Receptors, and Enzymes as Targets of Psychopharmacological Drug Action**
**Neurotransmitter Transporters as Targets of Drug Action.**
Transporters control the transport of a neurotransmitter into and out of a neuron. They control the reuptake of neurotransmitters, which is the amount of time they spend in the synapse and thus affects communication between two neurons.
**Classification and Structure – p. 29**
Some of the neurotransmitter transporters have several transmembrane domains and are members of the SLC family. Their structure enables them to recognize specific chemical substances and transport them across the nerve cell membrane.
These transporters in general have 12 transmembrane regions. Plasma-membrane transporters include the SLC6 and SLC1 gene families.
**Monoamine Transporters (SLC6 Gene Family)– p. 31**
**Major Monoamine Transporters**
SERT = serotonin transporter
NET = norepinephrine transporter
DAT = dopamine transporter
Serotonin, norepinephrine, and dopamine transporters are members of the SLC6 family. Inhibitory drugs of these transporters may lead to higher levels of neurotransmitters in the synaptic cleft, which has significant therapeutic effects in psychiatric conditions.
**Other Neurotransmitter Transporters (SLC6 and SLC1 Gene Families)– p. 34**
**GABA and Glutamate**
GABA: There are several GABA transporters called GAT1–4.
Glutamate: Glutamate transporters are called EAAT1–5 and belong to the SLC1 family.
Other transporters control the levels of neurotransmitters such as GABA, glycine, and glutamate. Modifying these systems can also modify inhibitory or excitatory signaling and can have an impact on neurological and psychiatric symptoms.
**Histamine and Neuropeptide Transporters– p. 35**
Unlike monoamines, histamine and neuropeptides lack a presynaptic reuptake system. Their activity is regulated in other ways, such as being broken down by enzymes and diffused out of the cell.
**Vesicular Transporters: Subtypes and Function.– p. 35**
Neurotransmitters are taken into vesicles for release by vesicular transporters. They help to accumulate neurotransmitters within vesicles, ready for movement to the nerve cell for communication.
VMAT2 → serotonin, norepinephrine, dopamine, histamine
VAChT → acetylcholine
VIAAT → GABA
vGluT1–3 → glutamate
**Vesicular Transporters as Drug Targets– p. 35**
VMAT2 and other vesicular proteins can be influenced by psychotropic medications and stimulant drugs. Altered vesicular storage can significantly affect neurotransmitter release.
**G-Protein-Linked Receptors– p. 36**
These receptors have 7 membrane-spanning regions and convert binding of neurotransmitters into intracellular signals. The effects can be seen in the immediate receptor, but can also be seen in second messengers, proteins, and gene expression.
**Structure and Function**
The activity of receptors is not binary, but lies on a continuum from full activation to decreased activation. Agonists activate receptors; antagonists are molecules that don't activate receptors; partial agonists activate receptors, albeit not as strongly as full agonists; and inverse agonists decrease constitutive activity.
**G-Protein-Linked Receptors as Targets of Psychotropic Drugs– p. 36**
Several receptor types interact with psychotropic medications, including dopamine, serotonin, histamine, GABA, adrenergic, and melatonin receptors. The clinical effects of drugs vary depending on whether they stimulate, block, or stabilize receptor activity.
**The Agonist Spectrum**
Full agonist → Partial agonist → Antagonist → Inverse agonist
Full agonist: Creates maximum receptor activation and signal transduction.
Antagonist: Blocks agonist activity but does not independently activate the receptor. True antagonists are described as "silent".
Partial Agonist: Produces more activity than an antagonist; however, it has less activity than a full agonist.
_Partial agonists can function as stabilizers. When neurotransmitter activity is low, it increases activity; when full-agonist activity is high, it reduces activity to an intermediate level._
Light/rheostat analogy:
Full agonist = brightest light
Partial agonist = dimmed light but still shining
No agonist = light off
Inverse Agonist: Reduces receptor activity below baseline constitutive activity. Inverse agonists are above simple antagonists and are neither neutral nor silent. It produces a conformational transformation in the G-protein-linked receptor that stabilizes the inactive form.
Full agonist: ↑↑↑ activity
Partial agonist: ↑ activity
Antagonist: baseline
Inverse agonist: ↓ below baseline
**Enzymes as Sites of Psychopharmacological Drug Action -p. 45**
Enzymes are yet another pharmaceutical target. The effects of drugs can alter the synthesis and degradation mechanisms of neurotransmitters or alter how they are used in the cell, which can change the function of the neurons.
Enzymes convert a substrate into a product.
Substrate → binds active site → enzyme modifies substrate → product
Irreversible Inhibitor: Binds permanently to the enzyme and cannot be displaced by the substrate. Enzyme activity returns only after the cell synthesizes new enzyme molecules. Sometimes it is called a "suicide inhibitor." It is called this because it permanently inhibits the enzyme and therefore kills it.
Reversible Inhibitor: Can be displaced by the enzyme's substrate because it is able to compete with it. Whether the inhibitor or substrate predominates depends on factors such as relative affinity and concentration.
Important enzymes targeted by psychotropic drugs include:
MAO – monoamine oxidase
Acetylcholinesterase
GSK – glycogen synthase kinase
Lithium may inhibit GSK-3, potentially contributing to neuroprotective effects, long-term plasticity, and its antimanic/mood-stabilizing actions
**Cytochrome P450 Drug-Metabolizing Enzymes As Targets Of Psychotropic Drugs-p. 49**
CYP450 enzymes are mainly responsible for how medicines are metabolized in the body. Enzyme activity can vary, affecting drug concentration, efficacy, and the risk of adverse effects in treating psychological disorders, making metabolism a critical factor.
**Pharmacokinetics vs. Pharmacodynamics**
The CYP450 system is found primarily in the liver and gut and is important for drug metabolism.
Pharmacokinetics = what the body does to the drug:
A – Absorption
D – Distribution
M – Metabolism
E – Excretion
Pharmacodynamics = what the drug does to the body, including its mechanism of action, therapeutic effects, and adverse effects.
Important CYP450 enzymes listed.
CYP1A2, CYP2B6, CYP2D6, CYP2C9, CYP2C19, CYP3A4
Poor/intermediate metabolizer: ↓ metabolism → potentially ↑ drug concentrations and adverse effects.
Ultra-rapid metabolizer: ↑ metabolism → potentially ↓ drug concentrations and reduced effectiveness.
Pharmacogenomic testing and therapeutic drug monitoring can sometimes help guide treatment, particularly in treatment-resistant patients.
**Summary -p. 50**
Transporters regulate neurotransmitter movement, receptors convert the chemical signal into a cellular response, and enzymes regulate biochemical processes. Drugs that affect the brain's chemistry, or signaling systems, are called psychotropic drugs, and they are used to achieve therapeutic effects.
_Source: Stahl's Essential Psychopharmacology, Chapter 2, pp. 29–50._
**Stahl_Chapter_5_159-244.pdf**
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