Introduction: Serotonin (5-HT) is a key neurotransmitter involved in mood, gastrointestinal motility, nausea, vascular tone and platelet function. Understanding 5-HT receptor subtypes (5-HT1, 5-HT2, 5-HT3, 5-HT4), synthesis, metabolism and pharmacokinetics is essential for B.Pharm students studying pharmacology. 5-HT antagonists—such as ondansetron, granisetron, ketanserin, cyproheptadine and alosetron—are clinically important for antiemetic, antipsychotic adjunct, antimigraine and IBS therapies. This concise review emphasizes mechanisms of action, therapeutic uses, adverse effects, receptor coupling and drug interactions to deepen conceptual understanding and aid exam preparation. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which enzyme is the rate-limiting step in serotonin biosynthesis?
- Tryptophan hydroxylase (TPH)
- Aromatic L-amino acid decarboxylase (AAD)
- Monoamine oxidase A (MAO-A)
- Serotonin N-acetyltransferase
Correct Answer: Tryptophan hydroxylase (TPH)
Q2. The primary metabolic product measured in urine to assess peripheral serotonin turnover is:
- 5-Hydroxyindoleacetic acid (5-HIAA)
- 5-Hydroxytryptamine (5-HT)
- 5-Hydroxytryptophan (5-HTP)
- Melatonin
Correct Answer: 5-Hydroxyindoleacetic acid (5-HIAA)
Q3. Which 5-HT receptor subtype is a ligand-gated ion channel?
- 5-HT3
- 5-HT1A
- 5-HT2A
- 5-HT4
Correct Answer: 5-HT3
Q4. Activation of 5-HT2A receptors primarily signals via which pathway?
- Gq protein → phospholipase C → IP3/DAG
- Gi protein → decrease cAMP
- Gs protein → increase cAMP
- Ion channel opening for Na+ influx
Correct Answer: Gq protein → phospholipase C → IP3/DAG
Q5. Ondansetron exerts its antiemetic effect mainly by blocking which receptor?
- 5-HT3 receptor
- 5-HT2 receptor
- 5-HT1B receptor
- 5-HT4 receptor
Correct Answer: 5-HT3 receptor
Q6. Which clinical use is most characteristic of alosetron, a 5-HT3 antagonist?
- Diarrhea-predominant irritable bowel syndrome (IBS-D)
- Migraine abortive therapy
- Major depressive disorder
- Parkinson’s disease motor symptoms
Correct Answer: Diarrhea-predominant irritable bowel syndrome (IBS-D)
Q7. Which adverse effect is commonly associated with 5-HT3 antagonists like ondansetron?
- Constipation and headache
- Hyperprolactinemia
- Orthostatic hypotension
- Extrapyramidal symptoms
Correct Answer: Constipation and headache
Q8. Ketanserin and ritanserin are antagonists at which serotonin receptor subtype and are used clinically to:
- Block 5-HT2 receptors and lower blood pressure/vasospasm
- Block 5-HT3 receptors and treat nausea
- Block 5-HT1 receptors and abort migraine
- Block 5-HT4 receptors and enhance motility
Correct Answer: Block 5-HT2 receptors and lower blood pressure/vasospasm
Q9. Cyproheptadine has mixed pharmacology; its antagonism at serotonin receptors contributes to which therapeutic effect?
- Appetite stimulation and relief of serotonin syndrome symptoms
- Antidepressant action via SERT inhibition
- Direct antiemetic effect via 5-HT3 blockade
- Prokinetic action in gastroparesis
Correct Answer: Appetite stimulation and relief of serotonin syndrome symptoms
Q10. Which receptor subtype mediates presynaptic autoinhibition of serotonin release in many brain regions?
- 5-HT1A (autoreceptor)
- 5-HT2C
- 5-HT3
- 5-HT4
Correct Answer: 5-HT1A (autoreceptor)
Q11. A drug that is a 5-HT4 agonist would most likely produce which effect in the GI tract?
- Increased acetylcholine release and enhanced motility
- Decreased secretions and slowed transit
- Direct antagonism of 5-HT3-mediated nausea
- Vasoconstriction of mesenteric vessels
Correct Answer: Increased acetylcholine release and enhanced motility
Q12. Which statement about 5-HT1 receptor agonists (triptans) is true regarding interactions with serotonergic drugs?
- Concomitant use with SSRIs/SNRIs may increase risk of serotonin syndrome
- They potentiate the effect of 5-HT3 antagonists and reduce emesis
- They are safely combined with MAO inhibitors without concern
- They block platelet aggregation when used with aspirin
Correct Answer: Concomitant use with SSRIs/SNRIs may increase risk of serotonin syndrome
Q13. Which pharmacokinetic property is most relevant when considering ondansetron dosing in hepatic impairment?
- Hepatic metabolism by CYP enzymes reduces clearance
- Renal excretion as unchanged drug is predominant
- High plasma protein binding prevents hepatic effects
- Extensive enterohepatic recycling prolongs half-life
Correct Answer: Hepatic metabolism by CYP enzymes reduces clearance
Q14. Methysergide, a 5-HT2 antagonist used historically for migraine prophylaxis, is associated with which serious adverse effect?
- Retroperitoneal and pleural fibrosis
- Severe neutropenia
- Hepatic necrosis
- QT shortening
Correct Answer: Retroperitoneal and pleural fibrosis
Q15. Which receptor subtype is most directly implicated in nausea and vomiting induced by chemotherapy?
- 5-HT3 receptors on vagal afferents and area postrema
- 5-HT1A receptors in the dorsal raphe
- 5-HT2A receptors in the cortex
- 5-HT4 receptors in enteric neurons
Correct Answer: 5-HT3 receptors on vagal afferents and area postrema
Q16. Alosetron’s use is restricted because its major safety concern is:
- Ischemic colitis and severe constipation
- Hepatotoxicity leading to liver failure
- Severe hypertension and stroke
- Life-threatening arrhythmias due to QT shortening
Correct Answer: Ischemic colitis and severe constipation
Q17. Which of the following best defines a receptor antagonist in the context of 5-HT pharmacology?
- A ligand that binds the receptor and prevents endogenous 5-HT from activating it
- A ligand that binds and activates the receptor producing a partial response
- A molecule that increases 5-HT synthesis in presynaptic neurons
- A transporter inhibitor that increases extracellular 5-HT
Correct Answer: A ligand that binds the receptor and prevents endogenous 5-HT from activating it
Q18. Which technique is commonly used to measure serotonin levels or its metabolite 5-HIAA in biological samples during pharmacology studies?
- High-performance liquid chromatography (HPLC)
- Western blotting for receptor proteins
- Polymerase chain reaction (PCR)
- Magnetic resonance imaging (MRI)
Correct Answer: High-performance liquid chromatography (HPLC)
Q19. A novel drug shows competitive antagonism at 5-HT2A receptors in vitro. Which pharmacological property would best confirm competitive antagonism?
- Rightward shift of agonist dose–response curve with no change in maximal response
- Decrease in agonist potency with a reduction in maximal response
- Irreversible blockade that cannot be overcome by increasing agonist
- Allosteric modulation producing a biphasic response
Correct Answer: Rightward shift of agonist dose–response curve with no change in maximal response
Q20. Which statement about 5-HT transport (SERT) inhibitors is most accurate concerning serotonin antagonists?
- SERT inhibitors increase synaptic 5-HT and may potentiate effects of 5-HT agonists, but are not antagonists
- SERT inhibitors act as direct 5-HT receptor antagonists at high doses
- SERT inhibitors are used clinically as 5-HT3 antagonists for emesis
- SERT inhibitors degrade serotonin via MAO activation
Correct Answer: SERT inhibitors increase synaptic 5-HT and may potentiate effects of 5-HT agonists, but are not antagonists
Q21. Which adverse effect profile is characteristic of 5-HT2 antagonists like cyproheptadine and pizotifen?
- Sedation, weight gain and anticholinergic effects
- Severe extrapyramidal symptoms and akathisia
- Profound diuresis and electrolyte loss
- Excessive sweating and insomnia
Correct Answer: Sedation, weight gain and anticholinergic effects
Q22. A 5-HT3 antagonist would block which ionic conductance underlying its antiemetic action?
- Non-selective cation (Na+/K+) channel opening in vagal afferents
- Voltage-gated calcium channel current in CNS neurons
- Ligand-gated chloride influx causing hyperpolarization
- Potassium channel opening leading to hyperpolarization
Correct Answer: Non-selective cation (Na+/K+) channel opening in vagal afferents
Q23. Which 5-HT receptor subtype antagonism is primarily investigated for treatment of antipsychotic-induced weight gain?
- 5-HT2C antagonism
- 5-HT1A antagonism
- 5-HT3 antagonism
- 5-HT4 antagonism
Correct Answer: 5-HT2C antagonism
Q24. In designing a selective 5-HT2A antagonist, which off-target effect should be minimized because it can cause orthostatic hypotension?
- Alpha-1 adrenergic receptor blockade
- Beta-2 adrenergic receptor blockade
- Muscarinic M2 receptor antagonism
- Dopamine D2 receptor blockade
Correct Answer: Alpha-1 adrenergic receptor blockade
Q25. Which laboratory finding would you expect in carcinoid syndrome due to excess peripheral serotonin production?
- Elevated urinary 5-HIAA
- Low plasma histamine levels
- Decreased platelet aggregation due to low serotonin
- Marked hypokalemia from renal loss
Correct Answer: Elevated urinary 5-HIAA
Q26. Which statement about 5-HT3 antagonists’ cardiac safety is important for clinical practice?
- Certain agents can prolong QT interval and require caution with other QT-prolonging drugs
- They universally protect against arrhythmias by shortening QT
- They cause bradycardia by direct vagal stimulation in all patients
- They increase myocardial contractility and are contraindicated in heart failure
Correct Answer: Certain agents can prolong QT interval and require caution with other QT-prolonging drugs
Q27. A partial agonist at a 5-HT receptor would be expected to:
- Produce submaximal receptor activation and can antagonize full agonist effects
- Completely block receptor activation regardless of agonist concentration
- Increase receptor expression on the cell membrane
- Irreversibly inactivate the receptor via covalent binding
Correct Answer: Produce submaximal receptor activation and can antagonize full agonist effects
Q28. Which drug mechanism best explains how 5-HT2 antagonists can reduce migraine frequency?
- Inhibition of vasoconstrictive and pro-inflammatory 5-HT2-mediated cerebrovascular responses
- Direct blockade of trigeminal nerve conduction by sodium channel inhibition
- Promotion of platelet aggregation to stabilize vascular tone
- Enhancement of central serotonin reuptake to reduce pain signaling
Correct Answer: Inhibition of vasoconstrictive and pro-inflammatory 5-HT2-mediated cerebrovascular responses
Q29. Which factor most influences the central nervous system penetration of a 5-HT antagonist?
- Lipophilicity and ability to cross the blood–brain barrier
- Renal clearance as unchanged drug
- Binding to plasma albumin only in peripheral tissues
- Number of hydroxyl groups affecting taste
Correct Answer: Lipophilicity and ability to cross the blood–brain barrier
Q30. For a B.Pharm student, which concept best explains why combining a 5-HT3 antagonist with dexamethasone improves antiemetic efficacy in chemotherapy?
- Different mechanisms target separate emetic pathways: vagal 5-HT3-mediated and inflammatory/central mechanisms
- Both drugs block the same receptor to double the blockade effect
- Dexamethasone directly antagonizes 5-HT3 receptors enhancing efficacy
- Combination reduces hepatic metabolism of the antagonist increasing plasma levels
Correct Answer: Different mechanisms target separate emetic pathways: vagal 5-HT3-mediated and inflammatory/central mechanisms
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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