Ring analogues of phenothiazines MCQs With Answer

Ring analogues of phenothiazines MCQs With Answer — This concise introduction helps B.Pharm students master ring analogues of phenothiazines through focused, exam‑oriented practice. Learn core concepts: the phenothiazine tricyclic scaffold, heteroatom substitutions, thioxanthene and other ring analogues, and how ring changes alter pharmacodynamics, pharmacokinetics and adverse effect profiles. Emphasis is on structure‑activity relationships (SAR), common synthetic modifications at C‑2 and N‑10, representative drugs (chlorpromazine, fluphenazine, thioridazine, prochlorperazine), and clinical implications like EPS, anticholinergic effects and metabolism by CYP enzymes. Ideal for revision in medicinal chemistry and pharmacology modules. ‘Now let’s test your knowledge with 50 MCQs on this topic.’

Q1. What is the defining structural feature of the phenothiazine core?

• A tricyclic ring system containing sulfur and nitrogen in the central ring
• A benzodiazepine fused ring with two nitrogen atoms
• A monocyclic aromatic ring with a sulfone group
• A steroidal tetracyclic nucleus with a sulfur atom

Correct Answer: A tricyclic ring system containing sulfur and nitrogen in the central ring

Q2. Which position on the phenothiazine nucleus is commonly substituted to increase antipsychotic potency?

• Position 1 (outer benzene ring)
• Position 2 (adjacent to the sulfur)
• Position 7 (para to nitrogen)
• Position 12 (terminal methyl)

Correct Answer: Position 2 (adjacent to the sulfur)

Q3. Replacement of the tertiary nitrogen side chain at N‑10 with different amine groups primarily affects which property?

• Color of the drug formulation
• Antipsychotic potency and side‑effect profile
• Ability to form salts for injection only
• Binding to albumin exclusively

Correct Answer: Antipsychotic potency and side‑effect profile

Q4. Which side‑chain type at N‑10 is typically associated with higher potency and increased extrapyramidal side effects?

• Aliphatic amines
• Piperazine derivatives
• Piperidine derivatives
• Primary amines

Correct Answer: Piperazine derivatives

Q5. Thioxanthenes are considered ring analogues of phenothiazines because they:

• Share a similar tricyclic scaffold with sulfur but differ at the bridgehead conformation
• Contain an extra oxygen in the central ring making them benzoxazines
• Have a steroidal backbone unrelated to phenothiazines
• Are simple alkylamines with no aromatic rings

Correct Answer: Share a similar tricyclic scaffold with sulfur but differ at the bridgehead conformation

Q6. Which phenothiazine analogue is widely used as an antiemetic rather than a primary antipsychotic?

• Chlorpromazine
• Prochlorperazine
• Fluphenazine
• Perphenazine

Correct Answer: Prochlorperazine

Q7. In SAR of phenothiazines, a chlorine substituent at position 2 generally:

• Reduces dopamine receptor affinity
• Increases lipophilicity and dopamine antagonism
• Makes the compound selective for serotonin receptors only
• Prevents hepatic metabolism entirely

Correct Answer: Increases lipophilicity and dopamine antagonism

Q8. A piperidine side chain on phenothiazines is most associated with which clinical features?

• High EPS, low anticholinergic effects
• Low potency, significant anticholinergic and hypotensive effects
• Exclusive antiemetic action with no CNS effects
• Selective serotonin reuptake inhibition

Correct Answer: Low potency, significant anticholinergic and hypotensive effects

Q9. Metabolic N‑dealkylation of phenothiazines primarily occurs in which organ?

• Kidney
• Liver (hepatic CYP450 enzymes)
• Lungs
• Pancreas

Correct Answer: Liver (hepatic CYP450 enzymes)

Q10. Which adverse effect is most characteristic of long‑term dopamine D2 blockade by phenothiazines?

• Renal tubular acidosis
• Tardive dyskinesia
• Optic neuritis
• Polycythemia vera

Correct Answer: Tardive dyskinesia

Q11. Which of the following is a typical example of a piperazine‑class phenothiazine?

• Chlorpromazine
• Thioridazine
• Fluphenazine
• Prothipendyl

Correct Answer: Fluphenazine

Q12. Structure‑activity relationship (SAR) indicates optimal side‑chain length between the tricyclic nucleus and terminal amine for antipsychotic activity is typically:

• 1 carbon atom
• 3 carbon atoms
• 6 carbon atoms
• 10 carbon atoms

Correct Answer: 3 carbon atoms

Q13. Which ring analogue change often reduces antipsychotic activity but may alter selectivity to other receptors?

• Substituting chlorine at C‑2
• Replacing sulfur with oxygen in the central ring
• Shortening the side chain by one carbon
• Introducing a methyl on the terminal amine

Correct Answer: Replacing sulfur with oxygen in the central ring

Q14. Phenothiazines primarily exert antipsychotic effects by blocking which receptor type?

• Beta‑adrenergic receptors
• Dopamine D2 receptors
• GABA‑A receptors
• NMDA receptors

Correct Answer: Dopamine D2 receptors

Q15. Which phenothiazine is notorious for causing cardiac arrhythmias at high doses due to QT prolongation?

• Fluphenazine
• Thioridazine
• Perphenazine
• Levomepromazine

Correct Answer: Thioridazine

Q16. Photosensitivity is a dermatologic adverse effect commonly seen with which modification in phenothiazines?

• Highly hydrophilic substituents
• Aryl halogenation such as 2‑chloro substitution
• Removal of the central sulfur atom
• Attachment of bulky polar side chains

Correct Answer: Aryl halogenation such as 2‑chloro substitution

Q17. Which biochemical process commonly converts phenothiazines into more polar metabolites for excretion?

• Glycosylation
• Sulfation and glucuronidation
• Peptide bond formation
• Direct renal filtration without metabolism

Correct Answer: Sulfation and glucuronidation

Q18. Among ring analogues, benzothiazepines differ from phenothiazines mainly by:

• Possessing a seven‑membered central ring instead of a six‑membered ring
• Having no heteroatoms at all
• Being non‑aromatic acyclic molecules
• Containing a steroid nucleus

Correct Answer: Possessing a seven‑membered central ring instead of a six‑membered ring

Q19. Which testable pharmacokinetic parameter is commonly increased by adding lipophilic substituents to the phenothiazine ring?

• Renal clearance
• Volume of distribution
• Protein synthesis rate
• Intestinal excretion

Correct Answer: Volume of distribution

Q20. A ring analogue that increases basicity of the terminal amine would most likely affect which pharmacokinetic property?

• Decrease in oral absorption regardless of pH
• Altered pKa leading to changes in ionization and tissue distribution
• Complete resistance to hepatic metabolism
• Conversion to a prodrug in the stomach

Correct Answer: Altered pKa leading to changes in ionization and tissue distribution

Q21. Which of the following phenothiazine derivatives is commonly used as a sedative and antiemetic rather than a strong antipsychotic?

• Chlorpromazine
• Promazine
• Fluphenazine
• Perphenazine

Correct Answer: Promazine

Q22. The presence of electron‑withdrawing groups on the phenothiazine ring tends to:

• Decrease receptor binding affinity uniformly
• Modulate potency and may increase D2 affinity depending on position
• Make the compound inactive in all assays
• Prevent crossing of the blood‑brain barrier entirely

Correct Answer: Modulate potency and may increase D2 affinity depending on position

Q23. Which laboratory enzyme system is most involved in the oxidative metabolism of phenothiazines?

• Monoamine oxidase (MAO)
• Cytochrome P450 (CYP450)
• Amylase
• Glutamate dehydrogenase

Correct Answer: Cytochrome P450 (CYP450)

Q24. Which clinical property is improved by converting a phenothiazine into a sulfoxide metabolite?

• Increased antipsychotic potency by tenfold
• Enhanced water solubility for renal elimination
• Permanent binding to plasma proteins
• Complete reversal of side effects

Correct Answer: Enhanced water solubility for renal elimination

Q25. Which of the following is NOT typically altered by ring analogue modification of phenothiazines?

• Receptor selectivity
• Therapeutic indication always switching to antibiotics
• Pharmacokinetic profile
• Side‑effect spectrum

Correct Answer: Therapeutic indication always switching to antibiotics

Q26. In drug design, replacing the central sulfur in phenothiazines with selenium would most likely:

• Have identical properties with no change
• Alter electronic and steric properties, affecting activity and metabolism
• Convert the molecule into a peptide
• Make it a carbohydrate derivative

Correct Answer: Alter electronic and steric properties, affecting activity and metabolism

Q27. Which side effect is more likely with low‑potency phenothiazines compared to high‑potency ones?

• Severe extrapyramidal symptoms
• Prominent anticholinergic and sedative effects
• Selective serotonin syndrome only
• Immediate nephrotoxicity

Correct Answer: Prominent anticholinergic and sedative effects

Q28. Which synthetic modification is most often used to produce depot (long‑acting) formulations of phenothiazine analogues?

• Attachment of a bulky hydrophilic PEG chain
• Formation of ester prodrugs with long fatty acids
• Removal of all ionizable groups
• Covalent linking to glucose molecules

Correct Answer: Formation of ester prodrugs with long fatty acids

Q29. Which of the following best describes the therapeutic classification of most phenothiazine ring analogues?

• Antihypertensives
• Typical antipsychotics and antiemetics
• Broad‑spectrum antibiotics
• Antidiabetic agents

Correct Answer: Typical antipsychotics and antiemetics

Q30. A student studying ring analogues notes that increased lipophilicity often increases CNS penetration. Which physicochemical property most directly correlates with lipophilicity?

• pKa
• Partition coefficient (log P)
• Molecular weight only
• Optical rotation

Correct Answer: Partition coefficient (log P)

Q31. Which adverse effect is commonly associated with phenothiazine use due to alpha‑adrenergic blockade?

• Hypertension
• Orthostatic hypotension
• Hyperthermia only
• Increased platelet aggregation

Correct Answer: Orthostatic hypotension

Q32. Which drug interaction risk is important when combining phenothiazines with other CNS depressants?

• Reduced risk of sedation
• Enhanced CNS depression and respiratory suppression
• No interaction expected clinically
• Immediate antagonism of antipsychotic action

Correct Answer: Enhanced CNS depression and respiratory suppression

Q33. Which laboratory monitoring may be indicated for patients on high doses of some phenothiazines with cardiotoxic potential?

• Serial ECGs for QT interval monitoring
• Daily complete thyroid panels
• Continuous liver ultrasound
• Monthly bone density scans

Correct Answer: Serial ECGs for QT interval monitoring

Q34. Which structural change often yields antiemetic activity while retaining dopaminergic blockade in peripheral chemoreceptor trigger zones?

• Complete removal of aromatic rings
• Specific N‑10 side‑chain modifications as in prochlorperazine
• Adding a large polar sugar moiety
• Converting to a peptide ester

Correct Answer: Specific N‑10 side‑chain modifications as in prochlorperazine

Q35. Which technique is most useful to characterize ring analogue structural modifications at the molecular level?

• Infrared spectroscopy (IR) and NMR
• Basic pH titration only
• Simple colorimetric paper test
• Counting crystals under a microscope

Correct Answer: Infrared spectroscopy (IR) and NMR

Q36. In medicinal chemistry, why are ring analogues created for a drug class like phenothiazines?

• To change color for branding purposes only
• To optimize potency, selectivity, safety and pharmacokinetics
• To make molecules edible as nutrients
• To eliminate all biological activity intentionally

Correct Answer: To optimize potency, selectivity, safety and pharmacokinetics

Q37. Which phenothiazine derivative is associated with a higher incidence of anticholinergic effects and is structurally a piperidine derivative?

• Fluphenazine
• Thioridazine
• Haloperidol
• Risperidone

Correct Answer: Thioridazine

Q38. Which clinical application exploits the dopamine‑blocking action of some phenothiazine analogues outside psychiatry?

• Antiviral therapy
• Antiemetic treatment for nausea and vomiting
• Insulin sensitization in diabetes
• Bone healing acceleration

Correct Answer: Antiemetic treatment for nausea and vomiting

Q39. Which adverse endocrine effect can result from dopamine D2 blockade by phenothiazine analogues?

• Hyperthyroidism
• Hyperprolactinemia leading to galactorrhea and amenorrhea
• Decreased cortisol only
• Rapid increase in growth hormone exclusively

Correct Answer: Hyperprolactinemia leading to galactorrhea and amenorrhea

Q40. When designing a new phenothiazine analogue to reduce EPS, a medicinal chemist might:

• Increase D2 affinity indiscriminately
• Alter ring or side chain to reduce central D2 blockade or increase 5‑HT2 blockade
• Remove all aromaticity
• Increase irreversible binding to dopamine receptors

Correct Answer: Alter ring or side chain to reduce central D2 blockade or increase 5‑HT2 blockade

Q41. Which clinical sign indicates acute extrapyramidal reaction from phenothiazines?

• Bradycardia with no motor symptoms
• Acute dystonia such as oculogyric crisis or neck spasm
• Gradual weight loss over months
• Increased visual acuity

Correct Answer: Acute dystonia such as oculogyric crisis or neck spasm

Q42. A B.Pharm student learning ring analogues should know that steric hindrance near the pharmacophore can:

• Have no effect on receptor binding
• Reduce receptor interaction and alter selectivity
• Always improve oral bioavailability
• Convert the drug into an enzyme

Correct Answer: Reduce receptor interaction and alter selectivity

Q43. Which formulation strategy can improve adherence by reducing dosing frequency for phenothiazine analogues?

• Increasing the frequency of immediate‑release tablets
• Developing depot intramuscular ester formulations
• Removing active drug and using placebo
• Administration via inhalation only

Correct Answer: Developing depot intramuscular ester formulations

Q44. Which property of phenothiazines contributes to anticholinergic side effects?

• Affinity for muscarinic acetylcholine receptors
• Strong agonism at GABA receptors
• Inhibition of acetylcholinesterase exclusively
• Selective blockade of angiotensin receptors

Correct Answer: Affinity for muscarinic acetylcholine receptors

Q45. A ring analogue showing decreased hepatic metabolism might lead to which clinical consequence?

• Shorter duration of action
• Prolonged half‑life and potential accumulation/toxicity
• Complete removal from bloodstream immediately
• Loss of oral activity only

Correct Answer: Prolonged half‑life and potential accumulation/toxicity

Q46. Which experimental model is commonly used in preclinical studies to assess antipsychotic potential of phenothiazine analogues?

• Forced swim test only
• Apomorphine or amphetamine‑induced behavioural assays in rodents
• Glucose tolerance testing in rabbits
• Plant seed germination assays

Correct Answer: Apomorphine or amphetamine‑induced behavioural assays in rodents

Q47. Which adverse hematologic reaction is a rare but serious risk with some phenothiazines?

• Aplastic anemia or agranulocytosis
• Immediate thrombosis in all patients
• Excessive erythropoiesis always
• Platelet doubling syndrome

Correct Answer: Aplastic anemia or agranulocytosis

Q48. In pharmaceutical analysis of ring analogues, which parameter helps confirm purity and identity of the synthesized analogue?

• Melting point, NMR and mass spectrometry data
• Only the smell of the compound
• Color change on exposure to sunlight only
• Simple pH measurement of a dilute solution

Correct Answer: Melting point, NMR and mass spectrometry data

Q49. Which statement about prodrug approaches for phenothiazine analogues is true?

• Prodrugs are always less effective clinically
• Prodrugs can improve solubility, absorption or depot formation and are activated in vivo
• Prodrugs are identical in chemical structure to active drugs
• Prodrugs eliminate all adverse effects permanently

Correct Answer: Prodrugs can improve solubility, absorption or depot formation and are activated in vivo

Q50. For exam preparation, why is it important for B.Pharm students to study ring analogues of phenothiazines in depth?

• Because they are exclusively used as antibiotics in pharmacy practice
• Because understanding structural modifications links medicinal chemistry to clinical pharmacology, safety, and formulation strategies
• Because they are irrelevant to modern pharmacy education
• Because copying structures is the only skill required

Correct Answer: Because understanding structural modifications links medicinal chemistry to clinical pharmacology, safety, and formulation strategies

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