Screening models for ANS activity – sympatholytics MCQs With Answer

Screening models for ANS activity – sympatholytics MCQs With Answer

This concise introduction explains screening models for autonomic nervous system (ANS) activity focusing on sympatholytics, tailored for B. Pharm students. Key concepts include sympatholytic mechanisms, adrenergic receptors (alpha1, alpha2, beta1, beta2), in vivo models (pithed rat, telemetry, anesthetized and conscious rodents), isolated tissue assays (rabbit aorta, atria, vas deferens, Langendorff heart), receptor binding and functional assays, pharmacodynamics (EC50, pA2, Schild analysis), and common drugs (prazosin, propranolol, phenoxybenzamine, clonidine, yohimbine). Emphasis is on designing, interpreting screening assays, and anticipating translational limitations and safety signals such as orthostatic hypotension and reflex tachycardia. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which experimental model is most appropriate to evaluate direct peripheral sympatholytic effects on blood pressure while eliminating central reflex influences?

• Pithed rat model
• Conscious telemetry rat
• Anesthetized intact cat
• Langendorff isolated heart

Correct Answer: Pithed rat model

Q2. Which isolated tissue preparation is commonly used to study alpha1-mediated vascular contraction and screen alpha1 antagonists?

• Rabbit aorta strip
• Guinea pig ileum
• Isolated rat atrium
• Isolated perfused kidney

Correct Answer: Rabbit aorta strip

Q3. Which agonist is most suitable as a standard to test alpha1 receptor-mediated vasoconstriction in screening assays?

• Phenylephrine
• Isoproterenol
• Atenolol
• Nitroprusside

Correct Answer: Phenylephrine

Q4. Which parameter from dose–response studies quantifies agonist potency as the concentration that produces 50% of maximal response?

• EC50
• Emax
• pA2
• Kd

Correct Answer: EC50

Q5. What does a Schild plot slope of ~1 typically indicate about an antagonist’s mechanism?

• Competitive (reversible) antagonism
• Irreversible non‑competitive antagonism
• Allosteric potentiation
• Inverse agonism

Correct Answer: Competitive (reversible) antagonism

Q6. Which measurement is obtained from receptor binding assays and reflects ligand affinity?

• Ki value
• Emax percentage
• Heart rate reduction
• pA2 value

Correct Answer: Ki value

Q7. Which screening model is best to evaluate cardiac chronotropic and inotropic effects of a candidate beta‑blocker?

• Langendorff isolated heart preparation
• Pithed rat systemic BP recording
• Rabbit aorta strip contraction
• Adrenal medulla perfusion

Correct Answer: Langendorff isolated heart preparation

Q8. Which drug is an irreversible alpha‑adrenoceptor antagonist often used as a reference for non‑competitive blockade?

• Phenoxybenzamine
• Prazosin
• Phentolamine
• Propranolol

Correct Answer: Phenoxybenzamine

Q9. In a functional antagonist assay, a reversible competitive antagonist typically causes which change to the agonist dose–response curve?

• Rightward parallel shift with unchanged Emax
• Decrease in Emax without shift
• Leftward shift with increased Emax
• No change in potency or efficacy

Correct Answer: Rightward parallel shift with unchanged Emax

Q10. Which technique provides continuous, high‑fidelity blood pressure and heart rate data in conscious small animals for chronic sympatholytic screening?

• Telemetry monitoring
• Tail‑cuff plethysmography
• Manual sphygmomanometer
• Electrocardiographic strip only

Correct Answer: Telemetry monitoring

Q11. Clonidine lowers sympathetic outflow primarily by agonism at which receptor subtype in the CNS?

• Alpha2 adrenoceptors
• Beta1 adrenoceptors
• Alpha1 adrenoceptors
• Muscarinic M2 receptors

Correct Answer: Alpha2 adrenoceptors

Q12. Which antagonist would reverse the central sympatholytic effects of clonidine by blocking alpha2 receptors?

• Yohimbine
• Prazosin
• Propranolol
• Phenoxybenzamine

Correct Answer: Yohimbine

Q13. Which radioligand is classically used to study beta‑adrenoceptor binding in vitro?

• [3H]-dihydroalprenolol
• [3H]-prazosin
• [125I]-insulin
• [14C]-glucose

Correct Answer: [3H]-dihydroalprenolol

Q14. Which in vitro tissue is commonly used to study adrenergic-mediated heart rate changes (chronotropy)?

• Isolated rat right atrium
• Rabbit aorta strip
• Guinea pig ileum
• Isolated vascular ring

Correct Answer: Isolated rat right atrium

Q15. A new compound reduces maximal contraction evoked by norepinephrine in rabbit aorta even at high agonist concentrations; this suggests which type of antagonism?

• Non‑competitive or irreversible antagonism
• Competitive reversible antagonism
• Pure agonism
• Allosteric positive modulation

Correct Answer: Non‑competitive or irreversible antagonism

Q16. When screening sympatholytics, which in vivo observation suggests clinically relevant orthostatic hypotension risk?

• Marked drop in systolic BP on standing or tail‑lift in conscious animals
• Mild resting bradycardia without BP change
• Isolated increase in urine output
• Enhanced locomotor activity in open field

Correct Answer: Marked drop in systolic BP on standing or tail‑lift in conscious animals

Q17. The pA2 value of an antagonist is best described as which of the following?

• Negative log of the antagonist equilibrium dissociation constant (measure of potency from Schild analysis)
• Maximum response produced by the antagonist
• Concentration of agonist producing 50% response
• Radioactivity bound in receptor assay

Correct Answer: Negative log of the antagonist equilibrium dissociation constant (measure of potency from Schild analysis)

Q18. Which feature of a beta‑blocker indicates it has intrinsic sympathomimetic activity (ISA)?

• Partial agonist activity at beta receptors producing less resting bradycardia
• Irreversible receptor blockade
• High alpha1 blockade causing vasodilation
• Complete antagonism with no agonist effects

Correct Answer: Partial agonist activity at beta receptors producing less resting bradycardia

Q19. Which control drug is most appropriate as a reference alpha1 antagonist in vascular screening assays?

• Prazosin
• Propranolol
• Clonidine
• Yohimbine

Correct Answer: Prazosin

Q20. In pithed rat experiments, why is the model useful for testing peripheral sympatholytics?

• Central nervous system reflexes are abolished, revealing direct peripheral effects
• Animals remain fully conscious and behaviorally reactive
• Heart is isolated for direct contractility measurement
• It measures renal clearance directly

Correct Answer: Central nervous system reflexes are abolished, revealing direct peripheral effects

Q21. Which experimental caveat must be considered when extrapolating in vitro receptor binding Ki to in vivo efficacy?

• Plasma protein binding and metabolic clearance can alter free drug concentration
• Ki directly predicts clinical side effects without adjustment
• In vitro assays measure heart rate changes accurately
• Binding assays capture blood pressure effects perfectly

Correct Answer: Plasma protein binding and metabolic clearance can alter free drug concentration

Q22. Which outcome indicates a competitive antagonist in Schild analysis when plotting log(dose ratio −1) versus log antagonist concentration?

• Linear plot with slope ≈1
• Exponential curve with slope >2
• Horizontal line indicating no antagonist effect
• Random scatter with no correlation

Correct Answer: Linear plot with slope ≈1

Q23. Which assay is most suitable to detect presynaptic alpha2 modulators that alter norepinephrine release?

• Isolated vas deferens or nerve‑stimulated tissue with neurotransmitter release measurement
• Langendorff heart for coronary flow only
• Rabbit aorta contracted by KCl exclusively
• Urine output in metabolic cages

Correct Answer: Isolated vas deferens or nerve‑stimulated tissue with neurotransmitter release measurement

Q24. Which effect is commonly observed after administration of a nonselective alpha antagonist like phentolamine?

• Reflex tachycardia due to vasodilation
• Profound bronchoconstriction
• Increased myocardial contractility via beta2 activation
• Marked sedation via cholinergic blockade

Correct Answer: Reflex tachycardia due to vasodilation

Q25. For high‑throughput screening of receptor selectivity between alpha1 and alpha2, which modern approach is most practical?

• Recombinant cell lines expressing individual receptor subtypes with automated functional readouts
• Whole‑animal telemetry exclusively
• Manual rabbit aorta strips only
• Adrenal gland histology

Correct Answer: Recombinant cell lines expressing individual receptor subtypes with automated functional readouts

Q26. Which experimental observation would suggest a drug is a beta2‑selective antagonist rather than beta1‑selective?

• Blocks isoproterenol‑induced bronchodilation more than heart rate reduction
• Reduces heart rate significantly but spares bronchial smooth muscle
• Produces profound nasal vasoconstriction
• Enhances catecholamine release from adrenal medulla

Correct Answer: Blocks isoproterenol‑induced bronchodilation more than heart rate reduction

Q27. When screening sympatholytics, why are anesthetized animal hemodynamic data sometimes misleading compared to conscious telemetry?

• Anesthesia alters autonomic tone and can blunt reflex responses
• Anesthesia always increases blood pressure consistently
• Conscious telemetry cannot measure heart rate accurately
• Anesthetized animals show enhanced locomotor artifacts

Correct Answer: Anesthesia alters autonomic tone and can blunt reflex responses

Q28. Which experimental finding indicates a candidate drug has strong peripheral sympatholytic action but poor central penetration?

• Large drop in vascular tone in pithed animals with minimal suppression of CNS‑mediated sympathetic behaviors
• Marked sedation with no peripheral BP change
• Reduction in central norepinephrine turnover with no peripheral BP effect
• High brain/plasma ratio with unchanged peripheral responses

Correct Answer: Large drop in vascular tone in pithed animals with minimal suppression of CNS‑mediated sympathetic behaviors

Q29. Which safety assay is important early in sympatholytic screening to detect potential bronchospasm risk from beta blockade?

• Bronchial smooth muscle relaxation/contraction assay (e.g., tracheal rings)
• Renal clearance measurement
• Coagulation time test
• Hepatocyte proliferation assay

Correct Answer: Bronchial smooth muscle relaxation/contraction assay (e.g., tracheal rings)

Q30. Which combination of assays gives the most comprehensive early profiling of a novel sympatholytic candidate?

• Receptor binding (Ki), isolated tissue functional assays (rabbit aorta, atria), pithed rat BP, and conscious telemetry
• Only in vitro microsomal stability assay
• Urine chemistry and hair microscopy
• Single high dose acute toxicity without pharmacology

Correct Answer: Receptor binding (Ki), isolated tissue functional assays (rabbit aorta, atria), pithed rat BP, and conscious telemetry

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