Neurotransmitters and MAOIs Quiz
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Questions and Answers

Which of the following neurotransmitters are considered catecholamines?

  • Serotonin
  • Epinephrine (correct)
  • Dopamine (correct)
  • GABA

What is the initial step in the biosynthetic pathway of catecholamines?

  • Production of dopamine from L-dopa
  • Conversion of tyrosine to norepinephrine
  • Conversion of L-phenylalanine to L-tyrosine (correct)
  • Formation of epinephrine from dopamine

What severe condition can be triggered by consuming aged cheese while on MAOIs?

  • Heartworm infection
  • Diabetes
  • Hypertensive crises (correct)
  • Anemia

What symptoms are typically experienced 1-2 hours after consuming tyramine-rich foods while on MAOIs?

<p>Severe headaches and palpitations (B)</p> Signup and view all the answers

What role does the enzyme tyrosine hydroxylase play in dopamine synthesis?

<p>Converts tyrosine into L-dopa (C)</p> Signup and view all the answers

Which of the following complications is NOT associated with hypertensive crises induced by MAOIs?

<p>Diabetic ketoacidosis (B)</p> Signup and view all the answers

Where are the dopaminergic nuclei primarily located in the brain?

<p>Substantia nigra and ventral tegmental area (C)</p> Signup and view all the answers

The 'cheese effect' primarily refers to the reaction caused by which substance in cheese?

<p>Tyramine (A)</p> Signup and view all the answers

What can result from D2 receptor inhibition in the striatum?

<p>Symptoms resembling Parkinson's disease (D)</p> Signup and view all the answers

Which medication has a lower tendency to produce side effects associated with D2 receptor inhibition?

<p>Clozapine (B)</p> Signup and view all the answers

How is noradrenaline synthesized from dopamine?

<p>By adding a hydroxyl group (D)</p> Signup and view all the answers

What role does noradrenaline play in the body?

<p>Regulating attention and impulsivity (C)</p> Signup and view all the answers

Where are the majority of noradrenaline neurons located?

<p>Locus coeruleus (B)</p> Signup and view all the answers

What process converts noradrenaline into adrenaline?

<p>Addition of a methyl group (B)</p> Signup and view all the answers

Which enzyme catalyzes the reaction that transforms dopamine into noradrenaline?

<p>Dopamine β-hydroxylase (DBH) (A)</p> Signup and view all the answers

What are the mechanisms for terminating the actions of dopamine, noradrenaline, and adrenaline?

<p>Reuptake and enzymatic degradation (B)</p> Signup and view all the answers

What leads to tolerance and dependence in opiate users?

<p>Adaptations in LC neurons (A)</p> Signup and view all the answers

What role does COMT play in neurotransmitter regulation?

<p>It breaks down dopamine and catecholamines. (A)</p> Signup and view all the answers

What risk is associated with consuming tyramine while on monoamine oxidase inhibitors (MAOIs)?

<p>Hypertensive crisis (A)</p> Signup and view all the answers

What consequence did MPTP contamination in meperidine have on individuals?

<p>It led to Parkinsonian symptoms. (B)</p> Signup and view all the answers

What does tyramine stimulate the release of, contributing to a hypertensive crisis?

<p>Norepinephrine and adrenaline (D)</p> Signup and view all the answers

How do DA receptors affect adenylyl cyclase activity?

<p>D1-like receptors stimulate its activity, while D2-like receptors inhibit it. (B)</p> Signup and view all the answers

Which food types are high in tyramine and should be avoided by those on MAOIs?

<p>Aged cheeses and cured meats (A)</p> Signup and view all the answers

What is the primary effect of selective MAO-B inhibitor selegiline?

<p>Helps mitigate oxidative stress in Parkinson's disease. (A)</p> Signup and view all the answers

Which symptoms are indicative of a hypertensive crisis?

<p>Headache and stiff neck (C)</p> Signup and view all the answers

What type of effect do D1-like receptors typically have?

<p>Excitatory effects stimulating adenylyl cyclase. (B)</p> Signup and view all the answers

Which treatments are commonly used for ADHD?

<p>Methylphenidate and amphetamines. (B)</p> Signup and view all the answers

Which aspect of dopamine's role is still not fully understood?

<p>How it contributes to psychotic symptoms. (D)</p> Signup and view all the answers

What is the mechanism by which antipsychotic drugs reduce symptoms of psychosis?

<p>By blocking D2 receptors in subcortical structures. (B)</p> Signup and view all the answers

What is the first step in the production of noradrenaline?

<p>Tyrosine is converted to Dopa. (D)</p> Signup and view all the answers

Which enzyme catalyzes the conversion of dopamine to noradrenaline?

<p>Dopamine-β-hydroxylase (DBH) (A)</p> Signup and view all the answers

How is the action of noradrenaline terminated in the presynaptic neuron?

<p>Through reuptake by the norepinephrine transporter (NAT) (C)</p> Signup and view all the answers

What enzyme is NOT involved in the breakdown of noradrenaline?

<p>Dopamine-β-hydroxylase (DBH) (D)</p> Signup and view all the answers

Which type of adrenoreceptor is generally inhibitory?

<p>α2 auto receptor (B)</p> Signup and view all the answers

Which enzyme metabolizes all catecholamines, including noradrenaline and adrenaline?

<p>Monoamine Oxidase (D)</p> Signup and view all the answers

What role do COMT inhibitors play in catecholamine action?

<p>They increase levels of catecholamines in synapses. (A)</p> Signup and view all the answers

Which of the following statements about adrenoreceptors is correct?

<p>Adrenoreceptors are all metabotropic. (C)</p> Signup and view all the answers

What is the primary function of auto receptors in the nervous system?

<p>Inhibit activity (B)</p> Signup and view all the answers

How do α-adrenergic receptors affect noradrenergic cell bodies upon activation?

<p>Decrease firing rate (B)</p> Signup and view all the answers

What effect does the locus coeruleus have on memory during situations of strong negative emotions?

<p>Enhances memory for danger-related stimuli (A)</p> Signup and view all the answers

What consequences arise from the activation of presynaptic α-ARs in the synaptic terminal?

<p>Inhibition of further NA synthesis (D)</p> Signup and view all the answers

Which system does the adrenergic function primarily target?

<p>Autonomic nervous system (D)</p> Signup and view all the answers

Which of the following is a potential application of β-adrenergic receptor antagonists?

<p>Reducing intensity of traumatic memories in PTSD (A)</p> Signup and view all the answers

Which of the following drugs is known to increase synaptic noradrenaline and is used to treat ADHD?

<p>Desipramine (A)</p> Signup and view all the answers

In what scenarios does increased firing of the locus coeruleus potentially lead to heightened anxiety?

<p>In response to perceived threats (D)</p> Signup and view all the answers

Flashcards

What are catecholamines?

A group of amine neurotransmitters synthesized from the amino acid tyrosine. They include dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline).

What is the 'cheese effect'?

The link between tyramine in foods and the potential for hypertensive crises in people taking monoamine oxidase inhibitors (MAOIs).

What is tyramine?

An amino acid found in aged cheese and other foods, which can trigger hypertensive crises in people on MAOIs.

What are monoamine oxidase inhibitors (MAOIs)?

A class of drugs that inhibit the activity of the enzyme monoamine oxidase, which breaks down neurotransmitters like dopamine, norepinephrine, and serotonin.

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What is the first step in catecholamine synthesis?

The conversion of L-phenylalanine to L-tyrosine, which is the first step in the synthesis of all catecholamines.

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What structural feature do catecholamines share?

Catecholamines, including dopamine (DA), norepinephrine (NA), and epinephrine (A), all share a catechol nucleus and an amine group.

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What is the first catecholamine synthesized?

The production of dopamine, which is the starting point for the synthesis of all other catecholamines.

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Where are dopaminergic nuclei located?

The substantia nigra and the ventral tegmental area (VTA) of the midbrain.

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What is COMT?

An enzyme that breaks down dopamine and other catecholamines alongside MAO.

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What are MAOIs?

A class of drugs used to treat Parkinson's disease by inhibiting the breakdown of dopamine.

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What is MPTP and its significance in Parkinson's disease?

A neurotoxin that causes Parkinson's disease by being converted to its toxic form, MPP+, particularly by the enzyme MAO-B.

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What is dopamine and its dual role in the brain?

A neurotransmitter that can have both excitatory and inhibitory effects depending on the receptor it binds to.

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What are D1-like receptors and their effects?

A type of dopamine receptor that stimulates adenylyl cyclase, leading to increased cAMP production and generally excitatory effects.

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What are D2-like receptors and their effects?

A type of dopamine receptor that inhibits adenylyl cyclase, reducing cAMP levels and generally inhibitory effects.

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How do antipsychotic drugs work in treating psychosis?

Drugs that block dopamine receptors in subcortical structures of the limbic forebrain to reduce psychotic symptoms like delusions and hallucinations.

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What is the dopamine transporter (DAT) and its function?

A dopamine transporter that removes dopamine from the synapse by reuptaking it back into the presynaptic neuron.

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What are the side effects of D2 receptor inhibition in the striatum?

Dopamine D2 receptor inhibition in the striatum can lead to side effects that resemble Parkinson's disease, often managed with anticholinergic medications.

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Why does clozapine have fewer Parkinson's-like side effects?

Clozapine exhibits a lower tendency to induce Parkinson's-like side effects due to its unique receptor binding profile, including a weaker affinity for D2 receptors, antagonism of 5HT2A receptors, and antagonism of muscarinic cholinergic receptors.

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How are dopamine agonists used in Parkinson's disease?

In Parkinson's disease, dopamine agonists like bromocriptine are used to alleviate symptoms by compensating for dopamine deficiency.

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What kind of agonists are being explored for Parkinson's treatment?

D3-preferring agonists, such as pramipexole and ropinirole, hold promise as effective treatments for Parkinson's disease.

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How is noradrenaline synthesized?

Noradrenaline is synthesized from dopamine by the addition of a hydroxyl group, catalyzed by the enzyme dopamine β-hydroxylase (DBH).

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How are the effects of noradrenaline terminated?

The termination of noradrenaline's actions involves reuptake via transporters and enzymatic degradation by MAO (Monoamine Oxidase) and COMT (Catechol-O-Methyltransferase).

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What are the main functions of noradrenaline?

Noradrenaline plays a crucial role in regulating attention and impulsivity, and is central to autonomic functions, including heart rate, blood pressure, and stress responses.

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Where are the majority of noradrenaline neurons located and how extensive are their connections?

The cell bodies of approximately 50% of noradrenaline neurons reside in the locus coeruleus, with each neuron making around 250,000 synapses, showcasing their extensive network connectivity.

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What are psychostimulants?

Drugs that increase dopamine and norepinephrine levels in the brain by acting on the dopamine (DAT) and serotonin transporters (SERT).

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What is monoamine oxidase (MAO)?

An enzyme responsible for breaking down monoamines, including tyramine, in the body. MAOIs inhibit this enzyme, leading to an increase in tyramine levels.

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Catecholamine Synthesis: Step 1

Tyrosine is converted to Dopa, then to dopamine. Dopamine is loaded into synaptic vesicles by VMAT.

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Catecholamine Synthesis: Step 2

Dopamine is transformed into noradrenaline inside the synaptic vesicles using the enzyme DBH.

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Catecholamine Synthesis: Step 3

Noradrenaline is released from vesicles and then converted into adrenaline by the enzyme PNMT.

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Catecholamine Synthesis: Step 4

Adrenaline produced in step 3 is then packaged back into synaptic vesicles via VMAT.

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Termination of NA and Adrenaline: Reuptake

The reuptake process removes both noradrenaline and adrenaline back into the presynaptic terminal.

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Termination of NA and Adrenaline: Enzymatic Breakdown

Enzymes MAO and COMT break down both noradrenaline and adrenaline.

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COMT Inhibitors

COMT Inhibitors (e.g., entacapone) prolong the effects of dopamine and norepinephrine by blocking their breakdown.

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Adrenergic Receptors

Adrenergic receptors are categorized into groups: β1, β2, β3, and α1 (postsynaptic) and α2 (presynaptic).

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What are auto receptors?

Receptors that are located on the presynaptic neuron, meaning they are located on the neuron releasing the neurotransmitter. They can modulate the release of the neurotransmitter itself, creating a negative feedback loop.

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What are alpha-adrenergic receptors (α-ARs)?

Alpha-adrenergic receptors are a type of receptor that is activated by the neurotransmitter norepinephrine (NA). They are found on both pre- and postsynaptic neurons, and their activation can lead to a variety of effects, including vasoconstriction, bronchodilation, and increased heart rate.

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What is the locus coeruleus (LC)?

The locus coeruleus (LC) is a brain region that is responsible for producing norepinephrine (NA), a neurotransmitter that is involved in arousal, attention, and stress responses.

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What is noradrenaline (NA)?

Norepinephrine is a neurotransmitter involved in many physiological processes, including alertness, arousal, and stress response. It is released by the locus coeruleus in the brain.

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What are beta-adrenergic receptor antagonists?

Beta-adrenergic receptor antagonists are a class of drugs that block the action of beta-adrenergic receptors. They are used in the treatment of high blood pressure (hypertension), angina, and other conditions.

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What is the amygdala?

The amygdala is a brain region that is involved in processing emotions, especially fear and anxiety. It also plays a role in memory formation, particularly for emotionally charged events.

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What is the norepinephrine transporter (NAT)?

Norepinephrine transporter (NAT) is a protein that is responsible for removing norepinephrine from the synaptic cleft, which is the space between neurons where communication occurs.

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What is post-traumatic stress disorder (PTSD)?

Post-traumatic stress disorder (PTSD) is a mental health condition that can develop after a traumatic event. Symptoms can include flashbacks, nightmares, avoidance of reminders of the event, and emotional numbness.

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Study Notes

Catecholamines

  • Catecholamines are amine neurotransmitters made from tyrosine.
  • They include dopamine, norepinephrine, and epinephrine.

Case Study: "Cheese Effect"

  • A British pharmacist observed wife's headaches after eating cheese while taking MAOIs.
  • Aged cheese contains high tyramine levels, triggering hypertensive crises in MAOI users.
  • This was reported in 1962 (Dally & Taylor).
  • Cheese (cooked or raw) caused blood pressure spikes from 160/90 to 220/115 mmHg.

Symptoms and Complications

  • Symptoms include severe headaches, heart pounding, and palpitations.
  • Time between eating and symptoms: 1-2 hours.
  • Potential complications include subarachnoid hemorrhage, hemiplegia, intracranial hemorrhage, cardiac arrhythmias, cardiac failure, pulmonary edema, and death.

Catecholamine Synthesis from Tyrosine

  • Catecholamines are synthesized from L-phenylalanine, which is converted to L-tyrosine.
  • Catecholamines contain a catechol group and an amine group.
  • Dopamine synthesis is a two-step process:
    • Tyrosine is actively transported into the brain.
    • Tyrosine hydroxylase converts tyrosine to L-dopa.
    • Dopa decarboxylase converts L-dopa to dopamine.

Dopaminergic Nuclei Location

  • Dopamine neurons are located in the substantia nigra and ventral tegmental area (VTA).
  • Substantia nigra neurons form the nigrostriatal pathway, crucial for motor control.
  • VTA neurons form the mesocorticolimbic pathway, involved in reward, reinforcement, and behavior.
  • Parkinson's disease is associated with loss of dopamine neurons in the substantia nigra.

Tyrosine Hydroxylase (TH)

  • TH is the rate-limiting enzyme in catecholamine synthesis.
  • Tyrosine transport across the blood-brain barrier is active transport.

Regulation of Tyrosine Hydroxylase (TH) Activity

  • TH activity increases with catecholamine release.
  • Stimuli such as chronic stress, caffeine, nicotine, or morphine upregulate TH.
  • Stimuli such as antidepressants downregulate TH.
  • L-dopa for Parkinson's disease treatment: Increased dopamine synthesis achieved by peripheral L-dopa administration, bypassing TH step.

Dopamine Termination

  • Dopamine is reuptaken into the terminal via the Dopamine Transporter (DAT).

Enzymatic Degradation

  • Dopamine is broken down by Monoamine Oxidase (MAO) and Catechol-O-Methyltransferase (COMT).
  • MAO exists in intracellular and extracellular forms, and exists as two isoforms MAO-A and MAO-B.
  • MAO-A is found in dopamine and norepinephrine neurons.
  • MAO-B is present in serotonin neurons.

MAO Inhibitors (MAOIs)

  • MAOIs are used to treat Parkinson's disease.
  • MPTP by-product of illicit drug synthesis causes PD.
  • Selegiline (deprenyl) is a selective MAO-B inhibitor.

Dopamine Receptors

  • Dopamine receptors (D1-D5) have both inhibitory and excitatory effects, depending on the receptor subtype.
  • D1-like receptors (D1 and D5) typically stimulate adenylyl cyclase (AC) activity.
  • D2-like receptors (D2, D3, and D4) typically inhibit adenylyl cyclase (AC) activity.

Dopamine Receptors in Diseases

  • Dopamine plays a role in cognitive control of behavior and working memory.
  • Psychostimulants increase dopamine levels by blocking the dopamine transporter (DAT).
  • Antipsychotic drugs block D2 receptors to reduce delusions and hallucinations associated with psychosis.
  • Parkinson's disease is managed with D2 agonists such as bromocriptine.

Noradrenaline from Dopamine

  • Noradrenaline is synthesized from dopamine by adding a hydroxyl group, catalyzed by dopamine β-hydroxylase (DBH), to dopamine.

Noradrenaline Location and Function

  • Noradrenaline neurons are in the locus coeruleus.
  • Noradrenaline plays a key role in attention and impulsivity; central to autonomic functions (heart rate, blood pressure).

Noradrenaline Termination

  • Noradrenaline is terminated by reuptake via transporters and enzymatic degradation (MAO and COMT).

Adrenaline from Noradrenaline

  • Adrenaline is synthesized from noradrenaline by the addition of a methyl group, catalyzed by phenylethanolamine N-methyltransferase (PNMT).

Adrenaline Mechanisms and Termination

  • Adrenaline mechanisms and termination are similar to dopamine and noradrenaline.

Auto Receptors

  • Autoreceptors on noradrenergic cells inhibit activity when stimulated.
  • This creates a negative feedback loop regulating signalling and reducing firing rates.

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Catecholamines PDF

Description

Test your knowledge on neurotransmitters, especially catecholamines, and their biosynthesis pathways. Understand the implications of monoamine oxidase inhibitors (MAOIs) and related conditions like the 'cheese effect'. This quiz covers key concepts in neurochemistry and pharmacology relevant to mental health and medication safety.

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