SAR of anticonvulsants MCQs With Answer

SAR of anticonvulsants MCQs With Answer is an essential revision tool for B. Pharm students studying how molecular features influence anticonvulsant activity. This concise introduction links pharmacophores, substituent effects, lipophilicity, ion channel interactions and metabolic considerations to drug potency, selectivity and adverse effects. Questions focus on common scaffolds—hydantoins, barbiturates, iminostilbenes, succinimides, valproates, benzodiazepines and newer scaffolds—highlighting mechanistic SAR (Na+ block, GABA potentiation, T-type Ca2+ inhibition, SV2A/α2δ binding). Clear MCQs with answers reinforce core concepts needed for exam success and rational drug design understanding. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which functional group in valproic acid primarily contributes to its anticonvulsant activity?

• A branched carboxylic acid
• An aromatic ring
• A hydantoin moiety
• A sulfonamide group

Correct Answer: A branched carboxylic acid

Q2. The hydantoin ring is the core pharmacophore of which classical anticonvulsant?

• Phenobarbital
• Phenytoin
• Carbamazepine
• Ethosuximide

Correct Answer: Phenytoin

Q3. Which structural feature of carbamazepine is most related to its mechanism as a Na+ channel blocker?

• Iminostilbene tricyclic skeleton
• Barbituric acid core
• GABA-mimetic side chain
• Thiophene ring

Correct Answer: Iminostilbene tricyclic skeleton

Q4. Increased lipophilicity in anticonvulsant molecules generally leads to:

• Reduced blood–brain barrier (BBB) penetration
• Increased renal clearance
• Enhanced BBB penetration and CNS potency
• Loss of activity due to decreased protein binding

Correct Answer: Enhanced BBB penetration and CNS potency

Q5. Which substitution on the aromatic ring of phenytoin analogs commonly decreases anticonvulsant potency?

• Small electron-donating groups
• Bulky electron-withdrawing groups at ortho position
• Unsubstituted phenyl rings
• Para-hydroxyl substitution

Correct Answer: Bulky electron-withdrawing groups at ortho position

Q6. Barbiturate anticonvulsants require which core structure for GABA-A receptor potentiation?

• Hydantoin ring
• Barbituric acid (pyrimidine-2,4,6-trione)
• Carboxylic acid chain
• Benzodiazepine diazepine ring

Correct Answer: Barbituric acid (pyrimidine-2,4,6-trione)

Q7. Which anticonvulsant’s SAR indicates that a carboxamide functionality enhances Na+ channel binding and potency?

• Ezogabine
• Lacosamide
• Gabapentin
• Topiramate

Correct Answer: Lacosamide

Q8. Ethosuximide’s activity against absence seizures is primarily due to inhibition of which channel type?

• Voltage-gated sodium channels
• Voltage-gated T-type calcium channels
• GABA uptake transporters
• SV2A vesicular proteins

Correct Answer: Voltage-gated T-type calcium channels

Q9. Which structural change generally reduces metabolism by hepatic CYP enzymes and prolongs half-life?

• Addition of polar hydroxyl groups
• Introduction of steric hindrance near metabolically labile sites
• Replacing aromatic rings with small aliphatic groups
• Increasing the number of hydrogen bond donors

Correct Answer: Introduction of steric hindrance near metabolically labile sites

Q10. Levetiracetam’s anticonvulsant activity is linked to binding which target?

• GABA-A receptor benzodiazepine site
• Voltage-gated sodium channel inactivated state
• SV2A synaptic vesicle protein
• α2δ subunit of calcium channels

Correct Answer: SV2A synaptic vesicle protein

Q11. The presence of an acidic carboxyl group in some anticonvulsants typically results in:

• Increased CNS penetration
• High plasma protein binding and ionization at physiological pH
• Complete resistance to hepatic metabolism
• Direct agonism at GABA-A receptors

Correct Answer: High plasma protein binding and ionization at physiological pH

Q12. Which structural class is associated with potentiation of GABAergic neurotransmission via allosteric modulation?

• Benzodiazepines
• Hydantoins
• Succinamides
• Propionic acids

Correct Answer: Benzodiazepines

Q13. Which substituent on benzodiazepines increases potency and receptor affinity?

• Large polar groups on heterocycle
• Electron-withdrawing substituents at C7 (e.g., nitro, chloro)
• Removal of aromatic rings
• Introduction of a carboxylate group

Correct Answer: Electron-withdrawing substituents at C7 (e.g., nitro, chloro)

Q14. Gabapentin and pregabalin share which SAR feature crucial for α2δ binding?

• A lipophilic aromatic ring
• An amino acid-like structure with a cyclohexyl core
• An α-amino acid or amino acid mimic with appropriate spacing
• A barbiturate nucleus

Correct Answer: An α-amino acid or amino acid mimic with appropriate spacing

Q15. Which structural modification converts carbamazepine into the prodrug oxcarbazepine with altered metabolism?

• Reduction to a dihydro form
• Introduction of a keto group at the 10,11-position
• Replacing the iminostilbene with a hydantoin
• Adding a sulfonamide moiety

Correct Answer: Introduction of a keto group at the 10,11-position

Q16. Topiramate’s sulfamate moiety contributes to which pharmacological action?

• Inhibition of carbonic anhydrase and modulation of GABA/glutamate receptors
• Direct Na+ channel blockade only
• SV2A binding
• Acting as a benzodiazepine agonist

Correct Answer: Inhibition of carbonic anhydrase and modulation of GABA/glutamate receptors

Q17. The antiseizure activity of benzodiazepines is highly dependent on what stereochemical feature?

• Presence of an S-chiral center in the alkyl chain
• Planarity of the tricyclic scaffold
• Correct orientation of the fused diazepine and benzene rings
• Configuration of an aliphatic quaternary carbon

Correct Answer: Correct orientation of the fused diazepine and benzene rings

Q18. Which of the following is a key SAR principle: replacing an aromatic ring with a bioisosteric heterocycle often:

• Completely eliminates activity
• Has no effect on pharmacokinetics
• Can retain activity while altering metabolic profile and polarity
• Always increases toxicity

Correct Answer: Can retain activity while altering metabolic profile and polarity

Q19. A tertiary amine in anticonvulsant molecules commonly influences:

• Ability to form GABA conjugates
• Basicity, distribution, and interaction with acidic binding sites
• Conversion to a hydantoin under physiological conditions
• Direct activation of T-type Ca2+ channels

Correct Answer: Basicity, distribution, and interaction with acidic binding sites

Q20. Which moiety in tiagabine is important for its action as a GABA uptake inhibitor?

• Bicyclic hydantoin core
• Nipecotic acid derivative with lipophilic thiophene substituents
• Carboxylated valproate backbone
• Sulfone-linked benzodiazepine

Correct Answer: Nipecotic acid derivative with lipophilic thiophene substituents

Q21. Sulfonamide-containing anticonvulsants like zonisamide show which SAR-associated property?

• High selectivity for GABA-B receptors
• Inhibition of carbonic anhydrase and T-type Ca2+ channels
• Direct sodium channel agonism
• Complete resistance to renal excretion

Correct Answer: Inhibition of carbonic anhydrase and T-type Ca2+ channels

Q22. Which modification often improves water solubility of lipophilic anticonvulsants for formulation?

• Adding bulky hydrophobic groups
• Converting to a salt form or adding ionizable groups
• Removing polar functional groups
• Increasing aromaticity

Correct Answer: Converting to a salt form or adding ionizable groups

Q23. Which structural feature distinguishes eslicarbazepine acetate from carbamazepine and affects SAR?

• It is a prodrug yielding an S-licarbazepine metabolite with improved tolerability
• Contains a hydantoin ring instead of an iminostilbene core
• Has a barbiturate nucleus
• Possesses a sulfamate group like topiramate

Correct Answer: It is a prodrug yielding an S-licarbazepine metabolite with improved tolerability

Q24. Which SAR observation explains why small polar substituents near a drug’s ionizable center can lower CNS penetration?

• They increase lipophilicity
• They increase molecular size only
• They increase polarity and reduce passive diffusion across the BBB
• They make the molecule more basic

Correct Answer: They increase polarity and reduce passive diffusion across the BBB

Q25. Vigabatrin’s unique mechanism (irreversible GABA transaminase inhibition) is related to which structural feature?

• A bulky aromatic ring
• An unsaturated alkenyl chain that forms a covalent bond
• An amino acid-like structure that mimics GABA and leads to enzyme inactivation
• A hydantoin nucleus

Correct Answer: An amino acid-like structure that mimics GABA and leads to enzyme inactivation

Q26. Which SAR aspect accounts for the photosensitivity and rash seen with some aromatic anticonvulsants?

• Presence of hydantoin ring only
• Metabolic formation of reactive arene oxide intermediates from aromatic rings
• High water solubility
• Low plasma protein binding

Correct Answer: Metabolic formation of reactive arene oxide intermediates from aromatic rings

Q27. Which chemical change often reduces teratogenic risk in anticonvulsant analogs?

• Increasing formation of reactive metabolites
• Removing or modifying metabolically reactive aromatic functionalities
• Adding halogen atoms to aromatic rings
• Converting acids into esters that are rapidly hydrolyzed

Correct Answer: Removing or modifying metabolically reactive aromatic functionalities

Q28. Which feature of lacosamide differentiates its mechanism among Na+ channel blockers?

• It enhances slow inactivation of sodium channels via a small functionalized amino acid scaffold
• It is a barbiturate that increases GABAergic tone
• It binds SV2A like levetiracetam
• It blocks T-type Ca2+ channels exclusively

Correct Answer: It enhances slow inactivation of sodium channels via a small functionalized amino acid scaffold

Q29. SAR studies show that replacing a hydrogen with a fluorine on an aromatic anticonvulsant often:

• Greatly increases metabolic oxidation at that position
• Improves metabolic stability and may increase potency
• Removes affinity for CNS targets
• Converts the drug into a prodrug

Correct Answer: Improves metabolic stability and may increase potency

Q30. Which SAR principle explains why prodrugs like fosphenytoin were developed?

• To reduce aqueous solubility for oral dosing
• To improve parenteral tolerability, solubility or pharmacokinetics by temporary modification
• To permanently deactivate the parent compound
• To increase formation of reactive metabolites

Correct Answer: To improve parenteral tolerability, solubility or pharmacokinetics by temporary modification

Q31. Which molecular property is commonly optimized to reduce P-glycoprotein mediated efflux at the BBB?

• Increase polar surface area greatly
• Increase recognition motifs for P-gp
• Reduce bulky amphipathic regions that are P-gp substrates
• Add multiple positive charges

Correct Answer: Reduce bulky amphipathic regions that are P-gp substrates

Q32. Which feature is important in designing anticonvulsants acting on T-type Ca2+ channels?

• Large hydrophobic polyaromatic scaffolds only
• Small, flexible molecules with specific H-bonding patterns that fit the channel pore
• Incorporation of a barbiturate nucleus
• Presence of a quaternary ammonium

Correct Answer: Small, flexible molecules with specific H-bonding patterns that fit the channel pore

Q33. Which structural element is characteristic of stiripentol’s anticonvulsant SAR and contributes to GABAergic effects?

• Primary amine linked to a heterocycle
• Aromatic di-substitution providing lipophilicity and allosteric GABA potentiation
• Hydantoin ring
• Sulfamate moiety

Correct Answer: Aromatic di-substitution providing lipophilicity and allosteric GABA potentiation

Q34. Which SAR factor often correlates with a higher risk of drug–drug interactions via CYP induction?

• High polarity and rapid renal excretion
• Presence of planar lipophilic aromatic systems metabolized by CYPs
• Complete absence of aromatic rings
• Being a charged peptide-like molecule

Correct Answer: Presence of planar lipophilic aromatic systems metabolized by CYPs

Q35. Which modification in benzodiazepine analogs commonly reduces sedative side effects but retains anticonvulsant action?

• Increasing lipophilicity drastically
• Designing subtype-selective ligands that prefer GABA-A α2/α3 subunits over α1
• Removing all aromatic rings
• Adding a hydantoin ring

Correct Answer: Designing subtype-selective ligands that prefer GABA-A α2/α3 subunits over α1

Q36. Which SAR observation underlies the design of levetiracetam analogs with improved potency?

• Increasing aromatic bulk around the pyrrolidone core
• Optimizing the amide/pyrrolidone substituents to enhance SV2A binding
• Removing the pyrrolidone ring entirely
• Adding a barbiturate-like di-keto structure

Correct Answer: Optimizing the amide/pyrrolidone substituents to enhance SV2A binding

Q37. Which SAR rule helps explain why chiral anticonvulsants may have enantioselective activity?

• Enantiomers have identical protein binding and efficacy
• Different spatial arrangement can alter receptor binding and metabolism, giving different potency/toxicity
• Chirality only affects color, not activity
• All anticonvulsants are achiral, so this is irrelevant

Correct Answer: Different spatial arrangement can alter receptor binding and metabolism, giving different potency/toxicity

Q38. Which structural modification to phenytoin analogs increased water solubility and led to clinical prodrugs?

• Attachment of lipophilic esters
• Formation of phosphate esters (e.g., fosphenytoin)
• Complete removal of aromatic rings
• Conversion into barbiturate derivatives

Correct Answer: Formation of phosphate esters (e.g., fosphenytoin)

Q39. Which SAR feature often reduces cognitive side effects while maintaining anticonvulsant action?

• Non-selective CNS depressant scaffolds
• Targeting specific molecular sites (e.g., SV2A or α2δ) rather than global GABA potentiation
• Increasing overall lipophilicity regardless of target
• Maximizing sedative potency

Correct Answer: Targeting specific molecular sites (e.g., SV2A or α2δ) rather than global GABA potentiation

Q40. Which class’s SAR indicates that modifying carbonyl positions in the ureide-like ring can adjust duration of action?

• Benzodiazepines
• Barbiturates
• Hydantoins
• Gabapentinoids

Correct Answer: Barbiturates

Q41. Which structural property is typically targeted to reduce teratogenic risk while retaining efficacy?

• Increasing formation of epoxide metabolites
• Replacing metabolically reactive aromatic systems with less reactive heterocycles
• Adding multiple halogen atoms indiscriminately
• Promoting extensive CYP induction

Correct Answer: Replacing metabolically reactive aromatic systems with less reactive heterocycles

Q42. Which SAR insight explains why some anticonvulsants cause hyponatremia?

• They all inhibit renal sodium channels directly
• Structural similarity to ADH causes increased water retention
• Certain structures (e.g., carbamazepine/oxcarbazepine) alter renal water/sodium handling via ADH-like effects
• They chelate sodium in plasma

Correct Answer: Certain structures (e.g., carbamazepine/oxcarbazepine) alter renal water/sodium handling via ADH-like effects

Q43. Which structural modification is often used to improve selectivity for CNS targets over peripheral receptors?

• Increase peripheral basicity
• Introduce polar groups that reduce peripheral membrane permeation while retaining BBB penetration via transporter mechanisms
• Maximize the number of aromatic rings
• Remove all ionizable groups

Correct Answer: Introduce polar groups that reduce peripheral membrane permeation while retaining BBB penetration via transporter mechanisms

Q44. Which SAR characteristic of ezogabine (retigabine) is responsible for its unique potassium channel opener activity?

• Hydantoin ring
• Trifluoromethylated aromatic amine scaffolding that stabilizes KCNQ channels
• Carboxylic acid moiety mimicking GABA
• Sulfamate moiety like topiramate

Correct Answer: Trifluoromethylated aromatic amine scaffolding that stabilizes KCNQ channels

Q45. Why are bulky lipophilic substituents near active pharmacophores sometimes detrimental?

• They always increase potency
• They can hinder target binding due to steric clash and reduce solubility
• They eliminate the need for metabolism
• They universally decrease plasma protein binding

Correct Answer: They can hinder target binding due to steric clash and reduce solubility

Q46. Which SAR approach is useful to reduce formation of toxic metabolites?

• Designing sites for rapid formation of reactive epoxides
• Blocking metabolic hotspots with stable bioisosteres such as fluorine
• Increasing aromaticity without modification
• Enhancing CYP induction

Correct Answer: Blocking metabolic hotspots with stable bioisosteres such as fluorine

Q47. Which SAR observation underlies the design of anticonvulsants with dual mechanisms (e.g., Na+ block + GABA potentiation)?

• Combination of distinct pharmacophores in a single molecule to engage multiple targets
• Use of prodrugs that separate mechanisms temporally
• Elimination of polar groups to increase BBB penetration only
• Designing molecules that are only peripherally active

Correct Answer: Combination of distinct pharmacophores in a single molecule to engage multiple targets

Q48. Which feature in drug design reduces hypersensitivity risk associated with aromatic anticonvulsants?

• Maintaining unsubstituted aromatic rings prone to epoxidation
• Introducing heteroatoms or steric shields to prevent formation of reactive arene oxides
• Increasing metabolic activation pathways
• Encouraging formation of protein-reactive metabolites

Correct Answer: Introducing heteroatoms or steric shields to prevent formation of reactive arene oxides

Q49. SAR studies show that increasing a compound’s polar surface area beyond an optimal range usually causes:

• Enhanced passive BBB penetration
• Reduced oral absorption and CNS penetration
• Improved ability to cross cell membranes by diffusion
• No change in pharmacokinetics

Correct Answer: Reduced oral absorption and CNS penetration

Q50. Which SAR principle best guides optimization of potency while minimizing systemic adverse effects?

• Maximize nonspecific lipophilicity and metabolic activation
• Enhance target selectivity via precise pharmacophore tuning and reduce off-target interactions
• Eliminate all polar groups regardless of mechanism
• Make molecules as large and planar as possible

Correct Answer: Enhance target selectivity via precise pharmacophore tuning and reduce off-target interactions

G S Sachin

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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