Introduction: Screening models for CNS activity and general anaesthetics are essential in preclinical pharmacology for B. Pharm students. These models include in vitro assays (receptor binding, patch-clamp, brain slice electrophysiology) and in vivo tests (loss of righting reflex, MAC determination, EEG, behavioral assays). Understanding screening strategies helps evaluate anesthetic potency, mechanism of action (GABAA, NMDA), dose-response, ADME, toxicity, and therapeutic index. Modern approaches use high-throughput cellular screens, zebrafish larvae, and translational biomarkers such as burst suppression and bispectral index. Mastery of these models sharpens interpretation of safety pharmacology and drug development decisions. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which in vitro technique directly measures ion channel currents to assess anesthetic effects?
- Radioligand binding assay
- Patch-clamp electrophysiology
- Western blotting
- ELISA
Correct Answer: Patch-clamp electrophysiology
Q2. The minimum alveolar concentration (MAC) is best described as:
- The plasma concentration producing sedation in 50% of subjects
- The concentration in brain required for 50% receptor occupancy
- The alveolar concentration preventing movement to surgical stimulus in 50% of subjects
- The dose that causes toxicity in 50% of subjects
Correct Answer: The alveolar concentration preventing movement to surgical stimulus in 50% of subjects
Q3. Loss of righting reflex (LORR) in rodents is used to assess:
- Analgesic potency
- Anesthetic hypnotic effect
- Anti-inflammatory activity
- Cardiotoxicity
Correct Answer: Anesthetic hypnotic effect
Q4. The Meyer-Overton correlation links anesthetic potency to:
- Binding affinity to GABAA receptors
- Lipid solubility (oil/gas partition coefficient)
- Rate of hepatic metabolism
- Plasma protein binding
Correct Answer: Lipid solubility (oil/gas partition coefficient)
Q5. Which animal model is commonly used for high-throughput screening of CNS-active compounds including anesthetics?
- Non-human primates
- Zebrafish larvae
- Pigs
- Dogs
Correct Answer: Zebrafish larvae
Q6. Two-electrode voltage clamp in Xenopus oocytes is mainly used to study:
- Whole-animal behavioral responses
- Single receptor or ion channel function
- Systemic pharmacokinetics
- Inflammatory biomarkers
Correct Answer: Single receptor or ion channel function
Q7. Burst suppression on EEG during deep anesthesia indicates:
- Light sedation only
- Very deep cortical depression and high anesthetic dose
- Enhanced arousal
- Primary seizure activity
Correct Answer: Very deep cortical depression and high anesthetic dose
Q8. Which receptor is a primary target for many intravenous general anesthetics enhancing inhibitory neurotransmission?
- NMDA receptor
- GABAA receptor
- μ-opioid receptor
- Serotonin 5-HT3 receptor
Correct Answer: GABAA receptor
Q9. The hot plate and tail-flick tests mainly evaluate which pharmacological property?
- Anxiolytic activity
- Anesthetic hypnotic action
- Anticholinergic effects
Correct Answer: Analgesic activity
Q10. In brain slice electrophysiology, which advantage supports screening anesthetic effects?
- Intact whole-organ pharmacokinetics
- Controlled synaptic circuitry with preserved network activity
- Non-mammalian physiology only
- High-throughput in vivo behavior
Correct Answer: Controlled synaptic circuitry with preserved network activity
Q11. A high therapeutic index in anesthetic screening indicates:
- Narrow margin between effective and toxic doses
- Wide safety margin between effective and toxic doses
- High potency but high toxicity
- Unpredictable dose-response
Correct Answer: Wide safety margin between effective and toxic doses
Q12. Which endpoint is commonly used to determine anesthetic potency in small animal models?
- EC50 of receptor binding in vitro
- MAC or ED50 for loss of movement
- IC50 for enzyme inhibition
- Maximum tolerated dose
Correct Answer: MAC or ED50 for loss of movement
Q13. Synergistic reduction of MAC when combining two drugs implies:
- Antagonism between agents
- Enhanced combined anesthetic effect requiring lower doses
- No interaction
- Increased toxicity without efficacy change
Correct Answer: Enhanced combined anesthetic effect requiring lower doses
Q14. In vitro radioligand binding screens primarily measure:
- Functional ion flux through channels
- Direct occupancy/affinity of ligands for receptors
- Behavioral endpoints in animals
- Electroencephalographic patterns
Correct Answer: Direct occupancy/affinity of ligands for receptors
Q15. Which assay helps evaluate anesthetic-induced neurotoxicity in developing brains?
- Adult MAC determination
- Neuronal apoptosis assays in organotypic cultures
- Radioligand displacement in liver microsomes
- Skin sensitization tests
Correct Answer: Neuronal apoptosis assays in organotypic cultures
Q16. Bispectral index (BIS) monitoring is used clinically to:
- Assess hepatic clearance
- Quantify depth of anesthesia from EEG signals
- Measure arterial blood gases
- Evaluate renal excretion
Correct Answer: Quantify depth of anesthesia from EEG signals
Q17. Which property of volatile anesthetics most strongly influences onset and recovery times in vivo?
- Metabolic clearance rate only
- Blood/gas partition coefficient
- Protein binding in muscle
- Plasma pH
Correct Answer: Blood/gas partition coefficient
Q18. Which model is best for initial assessment of GABAA modulation by a new compound?
- Whole-animal MAC testing
- Recombinant receptor electrophysiology (patch-clamp)
- Clinical trials
- Behavioral anxiety tests
Correct Answer: Recombinant receptor electrophysiology (patch-clamp)
Q19. Anesthetic-induced immobility during a noxious stimulus in animals is primarily mediated at the level of:
- Spinal cord motor circuits
- Peripheral nerves only
- Thalamic sensory relay exclusively
- Higher cortical cognition only
Correct Answer: Spinal cord motor circuits
Q20. Which in vivo behavioral test assesses motor coordination and can reveal anesthetic motor impairment?
- Rotarod test
- Forced swim test
- Elevated plus maze
- Open field exploration
Correct Answer: Rotarod test
Q21. Organotypic hippocampal slice cultures are useful because they:
- Lack synaptic connectivity
- Preserve native architecture and allow chronic exposure studies
- Require whole-animal anesthesia
- Are identical to in vivo pharmacokinetics
Correct Answer: Preserve native architecture and allow chronic exposure studies
Q22. A screening cascade for anesthetic development typically proceeds in which order?
- Clinical trials → animal MAC → in vitro receptor assays
- High-throughput in vitro assays → targeted electrophysiology → in vivo efficacy and safety
- Human EEG studies → zebrafish → receptor cloning
- Marketing studies → in vivo testing → in vitro confirmation
Correct Answer: High-throughput in vitro assays → targeted electrophysiology → in vivo efficacy and safety
Q23. Which observation would suggest an anesthetic acts primarily via NMDA receptor inhibition?
- Potentiation of GABAergic currents only
- Blockade of NMDA-evoked currents in patch-clamp studies
- Increase in MAC due to opioid coadministration
- Selective enhancement of glycine receptors exclusively
Correct Answer: Blockade of NMDA-evoked currents in patch-clamp studies
Q24. In pharmacological screening, EC50 refers to:
- The concentration causing 50% of maximal effect
- The dose causing death in 50% of animals
- The binding affinity equal to 50 nM
- The maximum effect achievable
Correct Answer: The concentration causing 50% of maximal effect
Q25. Which factor complicates direct translation of rodent anesthetic data to humans?
- Identical MAC values across species
- Species differences in receptor subunit expression and pharmacokinetics
- In vitro assays being more predictive than in vivo
- Human EEG being identical to rodent EEG
Correct Answer: Species differences in receptor subunit expression and pharmacokinetics
Q26. A MAC-sparing agent reduces required volatile anesthetic dose primarily by:
- Increasing hepatic metabolism of the anesthetic
- Enhancing sedative or analgesic pathways to reduce potency requirement
- Blocking anesthetic uptake in lungs
- Inducing tachycardia
Correct Answer: Enhancing sedative or analgesic pathways to reduce potency requirement
Q27. Which in vitro model allows study of network oscillations relevant to EEG without whole animal use?
- Hepatocyte cultures
- Organotypic cortical or hippocampal slices with field recordings
- Isolated peripheral nerve preparations
- Differentiated adipocytes
Correct Answer: Organotypic cortical or hippocampal slices with field recordings
Q28. Enantiomeric differences in anesthetic action are important because:
- Both enantiomers always have identical potency
- Different enantiomers may have different potency, receptor selectivity, or safety profiles
- Only racemic mixtures are legal to use
- Enantiomers never interact with ion channels
Correct Answer: Different enantiomers may have different potency, receptor selectivity, or safety profiles
Q29. Which screening endpoint most directly evaluates CNS depressant effect rather than analgesia?
- Tail-flick latency
- Loss of righting reflex (LORR)
- Von Frey mechanical threshold
- Hot plate withdrawal
Correct Answer: Loss of righting reflex (LORR)
Q30. For early safety pharmacology of anesthetics, which system is prioritized for assessment?
- Dermatologic irritation only
- Cardiovascular and respiratory systems
- Hair growth promotion
- Gastrointestinal flora alterations exclusively
Correct Answer: Cardiovascular and respiratory systems
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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