Serotonin Overview and Syndrome
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Questions and Answers

What is a primary advantage of newer antidepressants compared to TCAs?

  • Newer antidepressants affect neurotransmitter release more significantly
  • Newer antidepressants cause more sedation
  • Newer antidepressants have fewer side effects and are generally better tolerated (correct)
  • Newer antidepressants block more receptor types

Which of the following side effects is commonly associated with TCAs due to receptor blockade?

  • Weight loss
  • Nausea
  • Increased appetite
  • Postural hypotension (correct)

Which neurotransmitter's reuptake does cocaine inhibit?

  • Only serotonin
  • Only norepinephrine
  • Norepinephrine, dopamine, and serotonin (correct)
  • Dopamine and serotonin only

MDMA is known to cause lesions in which type of neurons?

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

How do amphetamines primarily affect neurotransmitter release?

<p>By causing neurotransmitters to leak out of synaptic vesicles (D)</p> Signup and view all the answers

What receptors does prucalopride primarily bind to?

<p>5-HT4 receptor with high affinity (C)</p> Signup and view all the answers

Which side effect is NOT typically associated with TCAs?

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

What is the primary mechanism for clearing serotonin from the synaptic cleft?

<p>Reuptake by serotonin transporter (A)</p> Signup and view all the answers

Which form of monoamine oxidase (MAO) is found primarily in serotonin neurons?

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

What is a known effect of MDMA due to its interaction with serotonin systems?

<p>Induction of serotonin efflux (D)</p> Signup and view all the answers

What role does tryptophan hydroxylase (TPH) play in serotonin production?

<p>It acts as the rate-limiting enzyme in serotonin synthesis. (D)</p> Signup and view all the answers

What characterizes atypical depression?

<p>Hypersomnia and hyperphagia (C)</p> Signup and view all the answers

Which of the following neurotransmitters is synthesized directly from tryptophan?

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

What is a potential risk associated with high doses of Selegiline?

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

What substance is produced when 5-HTP undergoes decarboxylation?

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

SSRIs are favored in treating depression due to their:

<p>Better tolerability and fewer side effects (A)</p> Signup and view all the answers

Which of the following mechanisms is primarily responsible for the removal of serotonin from the synapse?

<p>Reuptake or degradation by MAO (D)</p> Signup and view all the answers

Which serotonin receptor subtypes are involved in regulating serotonin release?

<p>5-HT1A, 5-HT1B, and 5-HT1D (B)</p> Signup and view all the answers

How does MAO A affinity for norepinephrine compare to MAO B affinity?

<p>MAO A shows higher affinity than MAO B (C)</p> Signup and view all the answers

Which of the following best describes the location of serotonergic nuclei in the brain?

<p>Midline raphe nuclei in the brain stem (B)</p> Signup and view all the answers

Which of the following is a reversible inhibitor of MAO A?

<p>Meclobemide (C)</p> Signup and view all the answers

What is the main function of the vesicular monoamine transporter (VMAT) in serotonergic neurons?

<p>To store serotonin in synaptic vesicles (D)</p> Signup and view all the answers

Which of the following drugs primarily targets serotonin and norepinephrine in the treatment of depression?

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

Which gene is primarily expressed in the brain and responsible for tryptophan hydroxylase activity?

<p>TPH2 (D)</p> Signup and view all the answers

What type of receptors are 5-HT3 receptors classified as?

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

Which hallucinogen acts as a partial agonist at 5HT2A receptors?

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

What was one of the initial uses for LSD before it became a recreational drug?

<p>Treatment for schizophrenia (B)</p> Signup and view all the answers

Selective 5HT2A receptor antagonists have been shown to block which effects in animal models?

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

What neurotransmitter reuptake does bupropion primarily inhibit?

<p>Dopamine (C)</p> Signup and view all the answers

Which type of antidepressants specifically target serotonin reuptake?

<p>Selective serotonin reuptake inhibitors (SSRIs) (B)</p> Signup and view all the answers

What is the role of the transmembrane proteins DAT, NAT, and SERT?

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

Which mechanism is believed to cause sensory disruptions from hallucinogens?

<p>Dense serotonin innervation of the cerebral cortex (D)</p> Signup and view all the answers

Flashcards

What is serotonin?

Serotonin (5-HT) is a neurotransmitter that plays a significant role in various physiological and psychological functions, including mood regulation, sleep, appetite, and learning. It is synthesized from the amino acid tryptophan.

How is serotonin cleared from the synapse?

Serotonin, like other monoamine neurotransmitters, is cleared from the synapse through two primary mechanisms: reuptake and degradation.

What is the precursor for serotonin synthesis?

Tryptophan is an essential amino acid, meaning it must be obtained from the diet. It is a precursor for the synthesis of serotonin.

What is the rate-limiting enzyme in serotonin synthesis?

TPH (tryptophan hydroxylase) is the rate-limiting enzyme in serotonin synthesis. This means its activity determines the overall rate of serotonin production.

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What are the two isoforms of TPH and their locations?

TPH1 is primarily expressed in peripheral tissues, while TPH2 is found mainly in the brain. This suggests different roles for serotonin in different parts of the body.

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Where are serotonergic cell bodies located?

The raphe nuclei are a group of nuclei located in the brainstem that are responsible for synthesizing and releasing serotonin.

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What is the role of caudal raphe nuclei in serotonin function?

Caudal raphe nuclei project to the spinal cord, contributing to the modulation of pain signals. This highlights a role for serotonin in pain processing.

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What is the role of rostral raphe nuclei in serotonin function?

Rostral raphe nuclei project to various brain regions, suggesting a broad influence of serotonin on brain function.

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Serotonin Reuptake

The process of serotonin (5HT) being taken back into the presynaptic neuron after being released into the synapse.

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Serotonin Transporter (SERT)

A protein located on the presynaptic neuron that is responsible for transporting serotonin back into the neuron.

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Monoamine Oxidase (MAO)

An enzyme that degrades serotonin (5HT) in the synapse, ultimately preventing its further action.

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MAO A

One of the main isoforms of MAO, found in dopaminergic and noradrenergic neurons.

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MAO B

The other major isoform of MAO, primarily found in serotonin neurons. Less effective at breaking down serotonin compared to MAO A.

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MAO Inhibitors (MAOI)

Drugs that inhibit the activity of MAO, causing an increase in the levels of serotonin and other neurotransmitters in the brain.

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Nonselective MAOIs

A type of MAOI that inhibits both MAO A and MAO B.

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RIMAs (Reversible Inhibitors of MAO A)

Types of MAOIs that preferentially inhibit MAO A, allowing for less dietary restrictions.

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What are ionotropic receptors?

A type of receptor that allows for direct ion flow across the membrane when activated. They play a crucial role in rapid cellular signaling by directly altering the membrane potential.

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What is a partial agonist?

A drug that binds to a receptor and partially activates it, producing a weaker response compared to a full agonist.

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What are hallucinogens?

A class of drugs that act as partial agonists at 5HT2A receptors, leading to changes in perception and consciousness. They are often referred to as psychedelic drugs.

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What is LSD (d-lysergic acid diethylamide)?

A member of the hallucinogen family that acts as a partial agonist at 5HT2A receptors, causing sensory distortions, visual illusions, hallucinations, and emotional shifts.

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What are neurotransmitter reuptake transporters?

Transmembrane proteins responsible for the reuptake of neurotransmitters from the synapse into the presynaptic terminal. They play a critical role in terminating neurotransmission.

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What are selective serotonin reuptake inhibitors (SSRIs)?

A class of medications that inhibit the reuptake of the neurotransmitter serotonin, thereby increasing its concentration in the synapse and enhancing its signaling.

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What are serotonin-noradrenaline reuptake inhibitors (SNRIs)?

A class of antidepressant medications that inhibit the reuptake of both serotonin and norepinephrine, leading to increased levels of both neurotransmitters in the synapse.

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What are tricyclic antidepressants (TCAs)?

A class of antidepressant medications that inhibit the reuptake of both serotonin and norepinephrine, but with varying selectivity. Some TCAs may also block other receptors, contributing to their side effects.

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What side effects are associated with TCAs?

Tricyclic antidepressants block α1 adrenergic receptors, H1 histamine receptors, and muscarinic cholinergic receptors, leading to side effects like postural hypotension, sedation, and anticholinergic symptoms.

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How do newer antidepressants differ from TCAs in terms of side effects?

Newer antidepressants, like SSRIs, SNRIs, and NRIs, have fewer side effects than TCAs and are generally better tolerated.

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How does cocaine affect neurotransmitter levels?

Cocaine blocks the reuptake of dopamine, norepinephrine, and serotonin, increasing their levels in the synapse.

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How do amphetamines influence neurotransmitter levels?

Amphetamines enter nerve terminals, disrupt vesicle function, and cause a reverse transport of neurotransmitters, leading to increased synaptic levels. They work on dopamine, norepinephrine, and serotonin.

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What are the effects of MDMA (ecstasy)?

MDMA (ecstasy) is an amphetamine derivative with stimulant and psychedelic effects. It increases serotonin levels but can cause serotonin neuron damage.

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What is the main target of prucalopride?

Prucalopride selectively binds to the 5-HT4 receptor with high affinity, demonstrating specificity for this receptor.

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What causes postural hypotension?

Postural hypotension is a side effect caused by blocking α1 adrenergic receptors, leading to a drop in blood pressure when changing positions.

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What are anticholinergic effects, and what causes them?

Anticholinergic effects, like dry mouth, constipation, urinary retention, and blurred vision, result from blocking muscarinic cholinergic receptors.

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Study Notes

Serotonin (5-HT)

  • Serotonin and catecholamines have related functions, pathways, and are targeted by drugs like psychostimulants, tricyclic antidepressants, and monoamine oxidase inhibitors.
  • Serotonin is synthesized from tryptophan, an amino acid obtained from the diet.
  • Tryptophan is hydroxylated then decarboxylated to form serotonin.
  • Serotonin is removed from the synapse via reuptake or degradation by MAO.
  • Serotonergic nuclei are in the midline of the brainstem, with projections to the spinal cord and various brain regions influencing pain signals.

Serotonin Syndrome

  • Characterized by increased anxiety, insomnia, shaking, tachycardia, body aches, fatigue, and hyperreflexia.
  • Often associated with medication changes (e.g., discontinuation, increasing dosage) involving serotonin and other neurotransmitters.
  • Symptoms usually resolve within a week of discontinuing the implicated drug.

Serotonin Synthesis and Metabolism

  • Key enzymes in serotonin synthesis include Tryptophan hydroxylase (TPH), which is the rate-limiting step, and aromatic L-amino acid decarboxylase (AADC).
  • Serotonin is stored in vesicles and released into the synapse. It's reabsorbed by the serotonin transporter (SERT) or broken down by monoamine oxidase (MAO).

Serotonin Receptors

  • Various serotonin receptor subtypes exist, classified as presynaptic (regulating serotonin release) or postsynaptic (mediating downstream signals) and ionotropic or metabotropic.
  • 5-HT1A, 5-HT1B, and 5-HT1D are presynaptic; 5-HT1E, 5-HT1F, and 5-HT2A-5-HT2C are postsynaptic.
  • 5-HT3 receptors are ionotropic, directly influencing ion flow.

Hallucinogens and Serotonin

  • Hallucinogens like LSD act as partial agonists at 5-HT2A receptors, causing perceptual changes.
  • Other hallucinogens (DMT, psilocybin, mescaline, and DOM) also have similar mechanisms of action.

Drugs Affecting Serotonin Transmission

  • MAOIs, like iproniazid, were initially used for tuberculosis but found to alleviate depression.
  • SSRIs (selective serotonin reuptake inhibitors) are commonly used antidepressants; they selectively inhibit the SERT.
  • TCAs (tricyclic antidepressants) affect both serotonin and norepinephrine reuptake.
  • SNRIs (serotonin-norepinephrine reuptake inhibitors) affect both serotonin and norepinephrine reuptake.
  • Drugs like cocaine and amphetamines affect neurotransmitter reuptake systems, including serotonin.

Other Key Information

  • Tryptophan hydroxylase (TPH) exists in two isoforms (TPH1 and TPH2).
  • Monoamine oxidase (MAO) exists as two isoforms (MAO-A and MAO-B). MAO-A and MAO-B are involved in the breakdown of monoamines like serotonin and dopamine.
  • Different drugs have different actions. Some drugs inhibit MAO and other inhibitors can enhance or block the reuptake of serotonin.

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Serotonin (5HT) PDF

Description

Dive into the intricacies of serotonin, its synthesis from tryptophan, and its crucial role in the brain. Explore the characteristics and implications of serotonin syndrome, which arises from medication changes affecting serotonin levels. This quiz will test your understanding of serotonin's functions, synthesis, and related disorders.

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