Screening models for CNS activity – antiepileptics MCQs With Answer

Screening models for CNS activity are essential in the discovery and optimization of antiepileptic drugs. B. Pharm students should understand in vivo seizure assays (MES, PTZ, kindling, audiogenic), in vitro systems (brain slice electrophysiology, cultured neurons), and complementary tools (zebrafish larvae, in silico models) that assess pharmacodynamics, pharmacokinetics, blood–brain barrier penetration, and safety pharmacology. Knowledge of predictive, construct, and face validity, dose–response metrics (ED50, TD50, therapeutic index), EEG biomarkers, and receptor/channel targets (GABA, sodium, calcium, glutamate) helps translate preclinical findings to clinical candidates. This introduction highlights experimental design, endpoint selection, and limitations relevant to antiepileptic screening. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which in vivo model is most predictive for screening drugs that prevent generalized tonic–clonic seizures by blocking voltage-gated sodium channels?

• PTZ-induced seizure test
• Maximal electroshock (MES) seizure test
• Kindling model
• Zebrafish locomotor assay

Correct Answer: Maximal electroshock (MES) seizure test

Q2. The PTZ seizure model is primarily used to identify compounds effective against which seizure type?

• Focal seizures with secondary generalization
• Absence and myoclonic seizures
• Status epilepticus
• Febrile seizures

Correct Answer: Absence and myoclonic seizures

Q3. Which characteristic describes the kindling model relevant to antiepileptic screening?

• Acute chemical induction of generalized seizures
• Progressive development of permanent hyperexcitability after repeated subthreshold stimulation
• High-throughput screening in larval zebrafish
• Direct measurement of GABA release in vitro

Correct Answer: Progressive development of permanent hyperexcitability after repeated subthreshold stimulation

Q4. In vitro brain slice electrophysiology is most useful during screening for which property of antiepileptic candidates?

• Assessment of systemic toxicity
• Evaluation of direct effects on neuronal excitability and synaptic transmission
• Blood–brain barrier permeability
• Renal clearance prediction

Correct Answer: Evaluation of direct effects on neuronal excitability and synaptic transmission

Q5. Which metric quantifies the dose at which 50% of animals show anticonvulsant effect in a screening assay?

• TD50
• ED50
• LD50
• IC50

Correct Answer: ED50

Q6. Therapeutic index (TI) in antiepileptic screening is defined as which ratio?

• ED50 / TD50
• TD50 / ED50
• LD50 / ED50
• IC50 / ED50

Correct Answer: TD50 / ED50

Q7. Which screening model is commonly used to study absence seizures and T-type calcium channel blockers?

• MES test in rats
• PTZ-induced seizure model
• Genetic models like GAERS (Genetic Absence Epilepsy Rats from Strasbourg)
• Pilocarpine status epilepticus model

Correct Answer: Genetic models like GAERS (Genetic Absence Epilepsy Rats from Strasbourg)

Q8. In zebrafish larval assays for anticonvulsant screening, which advantage is most relevant?

• Identical pharmacokinetics to humans
• High-throughput capacity with small compound volumes
• Ability to measure long-term cognitive outcomes
• Direct measurement of intracranial pressure

Correct Answer: High-throughput capacity with small compound volumes

Q9. Which of the following is a limitation of the MES model?

• It primarily detects drugs effective in absence seizures
• It cannot detect drugs that act on sodium channels
• It may miss agents effective only against focal seizures or absence epilepsy
• It is exclusively an in vitro assay

Correct Answer: It may miss agents effective only against focal seizures or absence epilepsy

Q10. Which receptor target is prominently assessed when screening antiseizure drugs that enhance inhibitory neurotransmission?

• NMDA receptor
• GABA-A receptor
• AMPA receptor
• mGluR5 receptor

Correct Answer: GABA-A receptor

Q11. EEG endpoints in preclinical seizure models most commonly measure which parameter?

• Renal electrical conductance
• Spike-and-wave discharges and seizure duration
• Hepatic enzyme activity
• Skin conductance

Correct Answer: Spike-and-wave discharges and seizure duration

Q12. Which chemical induces status epilepticus in rodents and is used to model temporal lobe epilepsy?

• Pentylenetetrazol (PTZ)
• Kainic acid
• Maximal electroshock
• Ethanol

Correct Answer: Kainic acid

Q13. Pilocarpine-induced status epilepticus is primarily used to model which clinical condition?

• Absence epilepsy
• Temporal lobe epilepsy and chronic spontaneous seizures
• Febrile seizures in neonates
• Alcohol withdrawal seizures

Correct Answer: Temporal lobe epilepsy and chronic spontaneous seizures

Q14. Which assay helps predict blood–brain barrier penetration during early screening?

• Rotarod motor coordination test
• Parallel artificial membrane permeability assay (PAMPA-BBB) or in vitro endothelial models
• Morris water maze
• In vivo liver microsome stability

Correct Answer: Parallel artificial membrane permeability assay (PAMPA-BBB) or in vitro endothelial models

Q15. Which safety pharmacology test is routinely performed to detect sedative or motor-impairing side effects of antiepileptic candidates?

• Tail-flick analgesia test
• Rotarod performance test
• Forced swim test
• Open field anxiety assay

Correct Answer: Rotarod performance test

Q16. A compound shows anticonvulsant effect in MES but not in PTZ. This suggests the compound likely acts on which target?

• T-type calcium channels
• GABAergic enhancement
• Voltage-gated sodium channels
• Glutamate NMDA receptor antagonism

Correct Answer: Voltage-gated sodium channels

Q17. Which in silico approach is commonly used in early screening to prioritize antiepileptic candidates?

• Homology modeling of liver enzymes only
• Molecular docking to target channels/receptors and ADMET prediction
• EEG waveform simulation
• Behavioral phenotype prediction from rodent data

Correct Answer: Molecular docking to target channels/receptors and ADMET prediction

Q18. During screening, a high clearance and low brain/plasma ratio indicate what problem for a CNS candidate?

• Excellent BBB penetration and sustained CNS exposure
• Poor brain exposure and rapid systemic elimination
• Selective accumulation in brain tissue
• High oral bioavailability

Correct Answer: Poor brain exposure and rapid systemic elimination

Q19. Which transporter is frequently evaluated because it can limit CNS penetration of antiepileptic drugs?

• Organic anion transporter 1 (OAT1)
• Glucose transporter 1 (GLUT1)
• P-glycoprotein (P-gp, ABCB1)
• Serotonin transporter (SERT)

Correct Answer: P-glycoprotein (P-gp, ABCB1)

Q20. Which electrophysiological measure in hippocampal slices indicates increased network excitability useful for screening?

• Reduced paired-pulse facilitation
• Increased spontaneous epileptiform bursts or population spikes
• Decreased input resistance uniformly
• Enhanced inhibitory postsynaptic currents only

Correct Answer: Increased spontaneous epileptiform bursts or population spikes

Q21. Which antiepileptic drug mechanism would be best detected in a PTZ model?

• Sodium channel blockade
• GABAergic potentiation
• Sodium–potassium ATPase inhibition
• Dopamine receptor antagonism

Correct Answer: GABAergic potentiation

Q22. In a screening cascade, which step should follow a promising in vitro electrophysiology hit?

• Direct Phase III clinical trials
• In vivo efficacy testing in at least one seizure model and ADME profiling
• Discontinuation due to high throughput origin
• Only in silico prediction refinement

Correct Answer: In vivo efficacy testing in at least one seizure model and ADME profiling

Q23. Which statement best describes face validity in seizure models?

• The model reproduces key phenomenological features of human epilepsy
• The model uses identical genetic mutations as humans
• The model is cheap and high-throughput
• The model focuses exclusively on pharmacokinetics

Correct Answer: The model reproduces key phenomenological features of human epilepsy

Q24. When interpreting ED50 and TD50 values, what does a narrow therapeutic index imply?

• The drug is very safe at therapeutic doses
• Therapeutic and toxic doses are close, raising safety concerns
• The drug has no pharmacodynamic effects
• The drug is ineffective in animal models

Correct Answer: Therapeutic and toxic doses are close, raising safety concerns

Q25. Which animal species is most commonly used for classic MES and PTZ screening assays?

• Nonhuman primates
• Rats and mice
• Guinea pigs only
• Dogs

Correct Answer: Rats and mice

Q26. Which of the following is an advantage of using genetic rodent models for epilepsy screening?

• They provide unlimited throughput like cell assays
• They model specific genetic causes and chronic seizure phenotypes
• They completely replace the need for human trials
• They guarantee identical drug responses as humans

Correct Answer: They model specific genetic causes and chronic seizure phenotypes

Q27. In high-content screening, what primary readout from cultured neurons might indicate anticonvulsant activity?

• Increased spontaneous calcium oscillation frequency
• Decreased synchronized neuronal bursting or reduced calcium transient amplitude
• Complete loss of neuronal viability
• Increased expression of liver enzymes

Correct Answer: Decreased synchronized neuronal bursting or reduced calcium transient amplitude

Q28. Which pharmacokinetic parameter is most critical to ensure adequate brain exposure during efficacy testing?

• High plasma protein binding only
• Brain-to-plasma concentration ratio and unbound brain concentration
• Rapid renal clearance
• High volume of distribution only in peripheral tissues

Correct Answer: Brain-to-plasma concentration ratio and unbound brain concentration

Q29. Which of the following best describes predictive validity of a preclinical seizure model?

• Ability to reproduce molecular pathology only
• Ability to predict clinical efficacy of treatments in humans
• Ability to be run at low cost
• Ability to measure PK parameters only

Correct Answer: Ability to predict clinical efficacy of treatments in humans

Q30. Which experimental endpoint would indicate neuroprotection after status epilepticus in chronic models?

• Increased neuronal loss in hippocampal CA1 and CA3 regions
• Reduced spontaneous recurrent seizure frequency and preserved hippocampal neurons
• Worsened cognitive deficits on maze tests
• Elevated proinflammatory cytokines only

Correct Answer: Reduced spontaneous recurrent seizure frequency and preserved hippocampal neurons

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.

Mail- Sachin@pharmacyfreak.com