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?

Serotonin neurons Signup and view all the answers

How do amphetamines primarily affect neurotransmitter release?

By causing neurotransmitters to leak out of synaptic vesicles Signup and view all the answers

What receptors does prucalopride primarily bind to?

5-HT4 receptor with high affinity Signup and view all the answers

Which side effect is NOT typically associated with TCAs?

Sexual dysfunction Signup and view all the answers

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

Reuptake by serotonin transporter Signup and view all the answers

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

MAO B Signup and view all the answers

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

Induction of serotonin efflux Signup and view all the answers

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

It acts as the rate-limiting enzyme in serotonin synthesis. Signup and view all the answers

What characterizes atypical depression?

Hypersomnia and hyperphagia Signup and view all the answers

Which of the following neurotransmitters is synthesized directly from tryptophan?

Serotonin Signup and view all the answers

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

Hypertensive crises Signup and view all the answers

What substance is produced when 5-HTP undergoes decarboxylation?

Serotonin Signup and view all the answers

SSRIs are favored in treating depression due to their:

Better tolerability and fewer side effects Signup and view all the answers

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

Reuptake or degradation by MAO Signup and view all the answers

Which serotonin receptor subtypes are involved in regulating serotonin release?

5-HT1A, 5-HT1B, and 5-HT1D Signup and view all the answers

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

MAO A shows higher affinity than MAO B Signup and view all the answers

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

Midline raphe nuclei in the brain stem Signup and view all the answers

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

Meclobemide Signup and view all the answers

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

To store serotonin in synaptic vesicles Signup and view all the answers

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

Tricyclic Antidepressants Signup and view all the answers

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

TPH2 Signup and view all the answers

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

Ionotropic receptors Signup and view all the answers

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

LSD Signup and view all the answers

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

Treatment for schizophrenia Signup and view all the answers

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

Hallucinatory effects Signup and view all the answers

What neurotransmitter reuptake does bupropion primarily inhibit?

Dopamine Signup and view all the answers

Which type of antidepressants specifically target serotonin reuptake?

Selective serotonin reuptake inhibitors (SSRIs) Signup and view all the answers

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

Neurotransmitter reuptake Signup and view all the answers

Which mechanism is believed to cause sensory disruptions from hallucinogens?

Dense serotonin innervation of the cerebral cortex Signup and view all the answers

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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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.