Exam #2- Psychopharmacology

Drug / Hormone: L-DOPA

Mechanism of Action: Precursor to dopamine; increases dopamine synthesis; Used For / Disorder: Parkinson’s disease

Drug / Hormone: 5-HTP

Mechanism of Action: Precursor to serotonin; increases serotonin synthesis; Used For / Disorder: Depression, insomnia, anxiety

Drug / Hormone: Physostigmine

Mechanism of Action: Inhibits acetylcholinesterase (ACh breakdown); Used For / Disorder: Myasthenia gravis, glaucoma

Drug / Hormone: Phenelzine

Mechanism of Action: MAOI; prevents breakdown of DA, NE, 5-HT; Used For / Disorder: Depression (atypical)

Drug / Hormone: Cocaine

Mechanism of Action: Blocks reuptake of DA, NE, 5-HT; Used For / Disorder: Drug of abuse; stimulant

Drug / Hormone: SSRIs / Antidepressants

Mechanism of Action: Block serotonin reuptake transporters; Used For / Disorder: Depression, anxiety, OCD

Drug / Hormone: Reserpine

Mechanism of Action: Blocks vesicular storage of DA, NE, 5-HT; Used For / Disorder: Former hypertension drug; causes depression

Drug / Hormone: Amphetamine

Mechanism of Action: Stimulates release of DA and NE; Used For / Disorder: ADHD, narcolepsy

Drug / Hormone: Fenfluramine

Mechanism of Action: Stimulates release of serotonin (5-HT); Used For / Disorder: Former appetite suppressant

Drug / Hormone: Clonidine

Mechanism of Action: Stimulates α2 autoreceptors (↓ NE release); Used For / Disorder: Hypertension, ADHD, opioid withdrawal

Drug / Hormone: Yohimbine

Mechanism of Action: Blocks α2 autoreceptors (↑ NE release); Used For / Disorder: Erectile dysfunction (research use)

Drug / Hormone: Benzodiazepines

Mechanism of Action: GABA_A receptor agonists; Used For / Disorder: Anxiety, insomnia, seizures

Drug / Hormone: Heroin / Morphine

Mechanism of Action: Opioid receptor agonists; Used For / Disorder: Pain relief, euphoria

Drug / Hormone: Nicotine

Mechanism of Action: Nicotinic ACh receptor agonist; Used For / Disorder: Stimulant, nicotine dependence

Drug / Hormone: THC

Mechanism of Action: CB1 receptor agonist; Used For / Disorder: Pain, nausea, appetite stimulation

Drug / Hormone: Caffeine

Mechanism of Action: Adenosine receptor antagonist; Used For / Disorder: Stimulant, alertness

Drug / Hormone: D₂ antagonists (antipsychotics)

Mechanism of Action: Block dopamine D₂ receptors; Used For / Disorder: Schizophrenia, bipolar disorder

Drug / Hormone: Cortisol / Cortisone / Prednisone / Dexamethasone

Mechanism of Action: Glucocorticoids; reduce inflammation, suppress immunity; Used For / Disorder: Inflammatory, autoimmune disorders, asthma

Drug / Hormone: Estradiol / Progesterone / Testosterone

Mechanism of Action: Steroid hormones from gonads; Used For / Disorder: Reproductive regulation, hormone therapy

Drug / Hormone: Insulin / Glucagon

Mechanism of Action: Pancreatic peptide hormones; regulate glucose; Used For / Disorder: Diabetes mellitus

Drug / Hormone: Melatonin

Mechanism of Action: Hormone from pineal gland; derived from 5-HT; Used For / Disorder: Sleep regulation, circadian disorders

Drug / Hormone: Prolactin (affected by DA blockers)

Mechanism of Action: DA antagonists increase prolactin release; Used For / Disorder: Antipsychotic side effects (galactorrhea, sexual dysfunction)

Enzyme: Tyrosine hydroxylase

Function: Converts tyrosine → L-DOPA (rate-limiting step); Associated Neurotransmitter(s): Dopamine, Norepinephrine, Epinephrine; Notes / Drug Interaction: Inhibited by AMPT → ↓ DA/NE synthesis

Enzyme: DOPA decarboxylase

Function: Converts L-DOPA → dopamine; Associated Neurotransmitter(s): Dopamine; Notes / Drug Interaction: Target in Parkinson’s therapy (L-DOPA increases DA)

Enzyme: Dopamine β-hydroxylase

Function: Converts dopamine → norepinephrine; Associated Neurotransmitter(s): Norepinephrine; Notes / Drug Interaction: Key enzyme in sympathetic neurons

Enzyme: Tryptophan hydroxylase

Function: Converts tryptophan → 5-hydroxytryptophan (5-HTP); Associated Neurotransmitter(s): Serotonin; Notes / Drug Interaction: Inhibited by PCPA → ↓ serotonin

Enzyme: Choline acetyltransferase (ChAT)

Function: Synthesizes acetylcholine from acetyl-CoA + choline; Associated Neurotransmitter(s): Acetylcholine; Notes / Drug Interaction: Defines cholinergic neurons

Enzyme: Tryptophan decarboxylase

Function: Converts tryptophan → tryptamine (precursor to 5-HT, melatonin); Associated Neurotransmitter(s): Serotonin pathway; Notes / Drug Interaction: Cooperates with tryptophan hydroxylase

Enzyme: Acetylcholinesterase (AChE)

Function: Breaks down acetylcholine in the synaptic cleft; Associated Neurotransmitter(s): Acetylcholine; Notes / Drug Interaction: Blocked by Physostigmine → ↑ ACh

Enzyme: Monoamine oxidase (MAO)

Function: Breaks down DA, NE, 5-HT in presynaptic terminal; Associated Neurotransmitter(s): Dopamine, Norepinephrine, Serotonin; Notes / Drug Interaction: Inhibited by Phenelzine (MAOI) → ↑ monoamines

Enzyme: Catechol-O-methyltransferase (COMT)

Function: Degrades catecholamines extracellularly; Associated Neurotransmitter(s): Dopamine, Norepinephrine, Epinephrine; Notes / Drug Interaction: Assists in catecholamine inactivation

Enzyme: Nitric oxide synthase (NOS)

Function: Converts arginine → nitric oxide (NO); Associated Neurotransmitter(s): Nitric oxide; Notes / Drug Interaction: Involved in vasodilation and synaptic plasticity

Enzyme: Tyrosine hydroxylase (TH)

Function: Converts tyrosine → L-DOPA; this is the rate-limiting step in catecholamine synthesis; Associated Neurotransmitter(s): Dopamine (DA), Norepinephrine (NE), Epinephrine (EPI); Clinical / Pharmacological Notes: Stimulated by stress; inhibited by α-methyl-para-tyrosine (AMPT) — used to treat pheochromocytoma (adrenal tumor)

Enzyme: DOPA decarboxylase

Function: Converts L-DOPA → dopamine; Associated Neurotransmitter(s): Dopamine; Clinical / Pharmacological Notes: Enzyme targeted indirectly by L-DOPA therapy for Parkinson’s disease

Enzyme: Monoamine oxidase (MAO)

Function: Breaks down dopamine, norepinephrine, and serotonin inside presynaptic terminals; Associated Neurotransmitter(s): Dopamine, Norepinephrine, Serotonin; Clinical / Pharmacological Notes: Inhibited by MAO inhibitors (MAOIs) like tranylcypromine (Parnate) — used to treat depression

Enzyme: Catechol-O-methyltransferase (COMT)

Function: Breaks down catecholamines extracellularly; Associated Neurotransmitter(s): Dopamine, Norepinephrine, Epinephrine; Clinical / Pharmacological Notes: Inhibited by entacapone (Comtan) — prevents DOPA breakdown in Parkinson’s disease

Enzyme: Protein kinase M zeta (PKMζ)

Function: Enzyme that helps maintain long-term memory traces; Associated Neurotransmitter(s): Not specific to a neurotransmitter; Clinical / Pharmacological Notes: Targeted by ZIP (zeta inhibitory peptide) — inhibits memory formation in research models

Receptor Subtype: D₁

Type / Mechanism: Excitatory; Functions: - Facilitates movement, motivation, and reward pathways; Notes / Clinical Relevance: Works together with D₂ system in basal ganglia circuits

Receptor Subtype: D₂

"Type / Mechanism: Inhibitory; Functions: - Serves as both autoreceptor (on presynaptic terminals) and postsynaptic receptor

• Inhibits dopamine release and neuronal firing; Notes / Clinical Relevance: Blocked by antipsychotic drugs (e.g., haloperidol, risperidone, clozapine) → treats schizophrenia

Excess D₂ activity linked to psychosis"

Receptor Subtype: D₃, D₄

Type / Mechanism: Inhibitory; Functions: - Involved in emotion, cognition, and motivation; Notes / Clinical Relevance: D₄ associated with novelty-seeking and behavioral regulation

Receptor Subtype: D₅

Type / Mechanism: Excitatory; Functions: - Supports learning, memory, and motor control; Notes / Clinical Relevance: Shares signaling pathways with D₁

Pathway: Nigrostriatal

Origin → Target: Substantia nigra → Striatum; Primary Function: Movement control; Clinical Note: Degeneration causes Parkinson’s disease

Pathway: Mesolimbic

Origin → Target: VTA → Nucleus accumbens; Primary Function: Reward, motivation; Clinical Note: Overactivity linked to addiction, psychosis

Pathway: Mesocortical

Origin → Target: VTA → Prefrontal cortex; Primary Function: Cognition, emotion; Clinical Note: Underactivity linked to negative symptoms of schizophrenia

Pathway: Tuberoinfundibular

Origin → Target: Hypothalamus → Pituitary; Primary Function: Inhibits prolactin release; Clinical Note: D₂ blockers increase prolactin → galactorrhea, sexual dysfunction

Receptor Subtype: α₁

"Type / Mechanism: Excitatory; Primary Locations (from slides): Blood vessels, bladder, smooth muscle, liver; Functions / Physiological Effects: - Vasoconstriction, ↑ blood pressure

• Contraction of bladder and pupil (mydriasis); Clinical / Drug Notes: Target of α₁ blockers (e.g., prazosin) for hypertension"

Receptor Subtype: α₂

"Type / Mechanism: Inhibitory; Primary Locations (from slides): Brainstem, presynaptic terminals, heart, GI tract; Functions / Physiological Effects: - Acts as autoreceptor → inhibits NE release

• Reduces sympathetic tone, lowers blood pressure; Clinical / Drug Notes: Clonidine = α₂ agonist (used for hypertension, ADHD, opioid withdrawal)"

Receptor Subtype: β₁

Type / Mechanism: Excitatory; Primary Locations (from slides): Heart; Functions / Physiological Effects: - ↑ heart rate, contractility, and conduction; Clinical / Drug Notes: β₁ blockers (e.g., propranolol, metoprolol) used for hypertension and anxiety

Receptor Subtype: β₂

Type / Mechanism: Excitatory; Primary Locations (from slides): Lungs, uterus, skeletal muscle, blood vessels; Functions / Physiological Effects: - Causes bronchodilation, vasodilation, and uterine relaxation; Clinical / Drug Notes: β₂ agonists (e.g., albuterol) used for asthma, COPD

Receptor Subtype: β₃

Type / Mechanism: Excitatory; Primary Locations (from slides): Adipose (fat) tissue; Functions / Physiological Effects: - Stimulates lipolysis (fat breakdown); Clinical / Drug Notes: Research target for obesity treatments

System: Central Dopaminergic System

Receptor Type(s): D₁–D₅; Key Function: Reward, motor control, cognition; Clinical Importance: Parkinson’s, schizophrenia, addiction

System: Sympathetic Nervous System (Adrenergic)

Receptor Type(s): α₁, α₂, β₁–β₃; Key Function: Cardiovascular, respiratory, and metabolic regulation; Clinical Importance: Hypertension, asthma, PTSD, anxiety

System: Autoreceptors (feedback)

Receptor Type(s): D₂ (for dopamine), α₂ (for NE); Key Function: Regulate neurotransmitter release; Clinical Importance: Drug targets: clonidine, antipsychotics

Drug: Reserpine

Mechanism of Action: Blocks VMAT (vesicular monoamine transporter) → prevents storage of dopamine, norepinephrine, and serotonin in synaptic vesicles → depletion of monoamines; Clinical Use / Relevance: Formerly used to treat hypertension; caused sedation and depression due to monoamine depletion

Drug: Amphetamine

Mechanism of Action: Stimulates release of dopamine and norepinephrine from presynaptic terminals; blocks reuptake to increase levels in synapse; Clinical Use / Relevance: ADHD, narcolepsy, and stimulant use disorder

Drug: Methamphetamine

Mechanism of Action: Similar to amphetamine; stronger CNS stimulant; releases DA and NE independent of neuron firing; Clinical Use / Relevance: Narcolepsy (rarely); substance abuse (illicit use)

Drug: MPTP

Mechanism of Action: Destroys dopaminergic neurons in the substantia nigra (nigrostriatal pathway); Clinical Use / Relevance: Used in research to create Parkinson’s disease models

Drug: L-DOPA

Mechanism of Action: Precursor to dopamine; increases dopamine synthesis; Clinical Use / Relevance: Parkinson’s disease treatment

Drug: Cocaine

Mechanism of Action: Blocks reuptake of dopamine, norepinephrine, and serotonin (non-selective monoamine transporter blocker); Clinical Use / Relevance: Drug of abuse; used experimentally in monoamine studies

Drug: Tricyclic Antidepressants (TCAs)

Mechanism of Action: Block reuptake of both norepinephrine and serotonin; Clinical Use / Relevance: Depression, chronic pain, anxiety

Drug: Reboxetine (Edronax)

Mechanism of Action: Selective norepinephrine reuptake inhibitor (NRI) → increases NE levels in prefrontal cortex; Clinical Use / Relevance: Depression, ADHD (off-label)

Drug: Atomoxetine (Strattera)

Mechanism of Action: Blocks norepinephrine transporter (NET) → increases NE levels in prefrontal cortex; Clinical Use / Relevance: ADHD treatment

Drug: Cocaine

Mechanism of Action: Inhibits DA, NE, and 5-HT reuptake → prolonged synaptic action; Clinical Use / Relevance: Drug of abuse, stimulant effect

Drug: Tranylcypromine (Parnate)

Mechanism of Action: Monoamine oxidase inhibitor (MAOI) → prevents breakdown of dopamine, norepinephrine, and serotonin; Clinical Use / Relevance: Depression (especially atypical depression)

Drug: Entacapone (Comtan)

Mechanism of Action: Catechol-O-methyltransferase (COMT) inhibitor → prevents breakdown of L-DOPA and dopamine; Clinical Use / Relevance: Parkinson’s disease (adjunct to L-DOPA therapy)

Drug: Clonidine

Mechanism of Action: α₂-adrenergic agonist → stimulates autoreceptors → inhibits norepinephrine release; decreases sympathetic output; Clinical Use / Relevance: Hypertension, ADHD, opioid withdrawal

Drug: Propranolol

Mechanism of Action: β-adrenergic blocker (non-selective) → blocks β₁ and β₂ receptors; Clinical Use / Relevance: Hypertension, anxiety, PTSD (reduces emotional memory)

Drug: Haloperidol

Mechanism of Action: D₂ receptor antagonist → blocks dopamine signaling in mesolimbic system; Clinical Use / Relevance: Schizophrenia, acute psychosis

Category: Vesicular blockers (VMAT blocker)

Examples: Reserpine; Main Mechanism: Prevent monoamine storage; Clinical Relevance: Experimental; causes depression

Category: Reuptake blockers

Examples: TCAs, Reboxetine, Atomoxetine, Cocaine; Main Mechanism: ↑ Monoamine signaling; Clinical Relevance: Antidepressant / stimulant

Category: Enzyme inhibitors

Examples: Tranylcypromine, Entacapone; Main Mechanism: ↓ Breakdown (↑ monoamine levels); Clinical Relevance: Depression, Parkinson’s

Category: Receptor agonists/antagonists

Examples: Clonidine, Propranolol, Haloperidol; Main Mechanism: Alter receptor-mediated signaling; Clinical Relevance: Hypertension, psychosis, PTSD

Category: Experimental / research tools

Examples: MPTP, ZIP; Main Mechanism: Destroy neurons / alter memory; Clinical Relevance: Research on Parkinson’s, learning

"Enzyme: Tryptophan hydroxylase (TPH)

— Two isoforms: TPH1 and TPH2"

"Function: Converts tryptophan → 5-hydroxytryptophan (5-HTP), the rate-limiting step in serotonin synthesis.; Location / Expression: TPH1 – found in gut and pineal gland (melatonin-secreting cells).

TPH2 – found in serotonergic neurons in the brain.; Clinical or Pharmacological Relevance: Inhibited by para-chlorophenylalanine (PCPA) → decreases serotonin synthesis.

A target for research in depression, anxiety, and stress."

Enzyme: Aromatic L-amino acid decarboxylase (AADC)

Function: Converts 5-hydroxytryptophan (5-HTP) → serotonin (5-HT).; Location / Expression: Found in serotonergic neurons (and other monoamine-producing cells).; Clinical or Pharmacological Relevance: Works with TPH to complete 5-HT synthesis.

Enzyme: Monoamine oxidase (MAO)

Function: Breaks down serotonin (5-HT) into 5-hydroxyindoleacetic acid (5-HIAA).; Location / Expression: Found in presynaptic terminals and mitochondria of neurons and glia.; Clinical or Pharmacological Relevance: MAO activity regulates serotonin levels; MAO inhibitors (MAOIs) increase 5-HT and are used in depression treatment.

Enzyme: VMAT (Vesicular monoamine transporter)

Function: Packages serotonin into synaptic vesicles for release.; Location / Expression: Presynaptic terminals of serotonergic neurons.; Clinical or Pharmacological Relevance: Blocked by reserpine → depletes serotonin stores.

Enzyme: Tryptophan hydroxylase inhibitors (like PCPA)

Function: Though not enzymes themselves, these agents directly inhibit TPH activity.; Location / Expression: —; Clinical or Pharmacological Relevance: Used experimentally to model serotonin depletion and study mood and aggression.

Receptor subtype: 5-HT₁A

"Receptor type: Metabotropic (inhibitory); Main functions / physiological effects: - Acts as autoreceptor on serotonergic neurons → ↓ 5-HT release

• Causes hyperpolarization and inhibition of firing

• Regulates anxiety, mood, and stress; Example drugs (from slides): Buspirone – partial agonist (anxiolytic)"

Receptor subtype: 5-HT₁B / 5-HT₁D

"Receptor type: Metabotropic (inhibitory); Main functions / physiological effects: - Vasoconstriction of cranial arteries

• Inhibits neurogenic inflammation

• Relieves migraine pain; Example drugs (from slides): Sumatriptan – agonist used for migraine"

Receptor subtype: 5-HT₂A

"Receptor type: Metabotropic (excitatory); Main functions / physiological effects: - Stimulates cortical neurons

• Involved in perception, hallucinations, and psychosis

• Regulates mood and sleep; Example drugs (from slides): LSD – agonists (hallucinogenic)

Ketanserin, Clozapine, Risperidone – antagonists; used in schizophrenia"

Receptor subtype: 5-HT₃

"Receptor type: Ionotropic (excitatory, ligand-gated cation channel); Main functions / physiological effects: - Mediates nausea and vomiting reflex (via vagus nerve)

• Involved in gut motility and visceral pain; Example drugs (from slides): Ondansetron (Zofran), – antagonist; treat chemotherapy-induced nausea"

Receptor subtype: 5-HT₆

Receptor type: Metabotropic (excitatory); Main functions / physiological effects: - Involved in learning and memory - Antagonists can enhance memory consolidation; Example drugs (from slides): 5-HT₆ antagonists – under development for Alzheimer’s disease, schizophrenia, cognitive deficits

Receptor subtype: 5-HT₇

Receptor type: Metabotropic (excitatory); Main functions / physiological effects: - Regulates circadian rhythms, thermoregulation, and mood; Example drugs (from slides): Investigational 5-HT₇ antagonists for depression and sleep disorders

Drug: Buspirone (BuSpar)

Receptor Target / Mechanism: Partial agonist at 5-HT₁A receptors (especially somatodendritic autoreceptors); Clinical Use: Anxiolytic (generalized anxiety disorder); non-sedating alternative to benzodiazepines