Preclinical screening models for autonomic nervous system drugs MCQs With Answer

Introduction: This quiz collection focuses on preclinical screening models used to evaluate drugs acting on the autonomic nervous system — both sympathetic and parasympathetic. It is designed for M.Pharm students preparing for advanced pharmacology and toxicology examinations and lab work. Questions cover isolated tissue preparations, in vivo animal models, electrical field stimulation, receptor subtype assays, bioassays for agonists/antagonists, Schild analysis, and common pitfalls in interpretation. The aim is to deepen conceptual understanding of experimental design, endpoint selection, species differences, and data analysis methods used to characterize autonomic drugs before clinical development. Thoughtful practice here strengthens skills needed for research and regulatory pharmacology.

Q1. Which isolated tissue preparation is classically used to evaluate muscarinic agonists and antagonists due to its robust cholinergic contractions?

• Isolated guinea pig ileum
• Rat vas deferens
• Rabbit aorta
• Mouse diaphragm

Correct Answer: Isolated guinea pig ileum

Q2. The pithed rat model is especially useful for studying which aspect of autonomic pharmacology?

• Central nervous system-mediated reflexes
• Direct peripheral cardiovascular responses without central reflex influence
• Gastrointestinal motility involving enteric reflexes
• Behavioral responses to anxiolytics

Correct Answer: Direct peripheral cardiovascular responses without central reflex influence

Q3. In an isolated rat vas deferens preparation, which receptor subtype mediates the twitch response primarily when stimulated by norepinephrine released by nerve stimulation?

• Beta-1 adrenergic receptors
• Alpha-1 adrenergic receptors
• Alpha-2 adrenergic receptors
• Muscarinic M2 receptors

Correct Answer: Alpha-1 adrenergic receptors

Q4. Electrical field stimulation (EFS) in isolated tissue baths is used mainly to:

• Directly activate smooth muscle receptors with chemical agonists
• Evoke neurotransmitter release from intrinsic nerves to study neurogenic responses
• Measure metabolic clearance of drugs by tissues
• Assess mitochondrial toxicity of compounds

Correct Answer: Evoke neurotransmitter release from intrinsic nerves to study neurogenic responses

Q5. Which model is most appropriate to assess beta-adrenergic chronotropic effects of a test compound?

• Isolated guinea pig ileum
• Isolated rabbit atria
• Rat ileum longitudinal strip
• Mouse urinary bladder strip

Correct Answer: Isolated rabbit atria

Q6. A compound shifts the concentration-response curve for acetylcholine to the right in a parallel manner without reducing the maximal response in isolated tissue. This pharmacological profile suggests the compound is likely a:

• Non-competitive antagonist
• Irreversible antagonist
• Competitive (surmountable) antagonist
• Allosteric agonist

Correct Answer: Competitive (surmountable) antagonist

Q7. The pA2 value obtained from Schild analysis provides information about which property of an antagonist?

• Intrinsic efficacy
• Affinity for the receptor
• Rate of metabolism
• Toxicity index

Correct Answer: Affinity for the receptor

Q8. Which in vivo test is commonly used to evaluate ganglionic blocking agents by measuring changes in resting blood pressure and orthostatic reflexes?

• Tail-flick test
• Mean arterial pressure measurement in conscious rats
• Forced swim test
• Hot-plate test

Correct Answer: Mean arterial pressure measurement in conscious rats

Q9. For assessing presynaptic alpha-2 adrenergic agonist activity that inhibits neurotransmitter release, which preparation is commonly used?

• Isolated guinea pig ileum with nicotinic blockade
• Rat hippocampal synaptosomes measuring norepinephrine release
• Mouse heart electromechanical coupling
• Isolated rabbit aortic ring constriction by phenylephrine

Correct Answer: Rat hippocampal synaptosomes measuring norepinephrine release

Q10. Which limitation is most important when extrapolating isolated tissue results to whole-animal autonomic responses?

• Reduced control over drug concentration in the bath
• Loss of integrated reflex and hormonal influences present in vivo
• Inability to measure receptor occupancy
• Lack of oxygenation of tissues

Correct Answer: Loss of integrated reflex and hormonal influences present in vivo

Q11. The isolated tracheal ring from guinea pig is frequently used to study which receptor-mediated responses?

• Muscarinic contraction and beta-adrenoceptor-mediated relaxation
• Alpha-1 mediated relaxation only
• NMDA receptor-mediated excitation
• Opioid receptor-mediated inhibition

Correct Answer: Muscarinic contraction and beta-adrenoceptor-mediated relaxation

Q12. Which assay is most suitable to quantify acetylcholinesterase inhibition by a test compound in a preclinical screen?

• Electrical field stimulation of vas deferens
• Ellman colorimetric assay on brain homogenate
• Measurement of mean arterial pressure in conscious dogs
• Glucose uptake in isolated muscle

Correct Answer: Ellman colorimetric assay on brain homogenate

Q13. When testing a new sympathomimetic agent, which experimental approach best distinguishes direct receptor activation from indirect (releasing) action?

• Perform assays only in vivo to see systemic effects
• Compare responses in tissues pretreated with a neuronal blocker like reserpine or tetrodotoxin
• Measure urine output after drug administration
• Use only receptor binding assays without functional tests

Correct Answer: Compare responses in tissues pretreated with a neuronal blocker like reserpine or tetrodotoxin

Q14. In autonomic pharmacology bioassays, why is it important to use cumulative concentration–response curves rather than single-dose measurements when possible?

• To avoid pharmacokinetic variability across animals
• To determine the full concentration–response relationship and calculate EC50 values
• To reduce tissue viability
• To mask antagonist effects

Correct Answer: To determine the full concentration–response relationship and calculate EC50 values

Q15. Which model is preferred to evaluate vagomimetic or vagolytic effects on gastrointestinal motility?

• Isolated guinea pig ileum with intact enteric innervation
• Isolated rat aorta strip
• In vitro cardiac Purkinje fibers
• Mouse isolated urinary bladder

Correct Answer: Isolated guinea pig ileum with intact enteric innervation

Q16. A novel antagonist produces a non-parallel rightward shift and depresses the maximal response in a concentration–response curve. This behavior most likely indicates:

• Competitive antagonism
• Non-competitive or irreversible antagonism
• Pure agonist activity
• Neutral allosteric modulation

Correct Answer: Non-competitive or irreversible antagonism

Q17. Which endpoint is commonly measured in isolated tissue assays to assess autonomic drug potency and efficacy?

• Change in contractile force or tension
• Blood glucose concentration
• Core body temperature
• Renal clearance rate

Correct Answer: Change in contractile force or tension

Q18. During receptor subtype identification for a new adrenergic drug, radioligand binding studies complement functional assays primarily by providing:

• Information on receptor distribution and affinity independent of efficacy
• Direct measurement of neurotransmitter release
• Data on in vivo reflex compensation
• Measurements of intracellular signaling kinetics in live animals

Correct Answer: Information on receptor distribution and affinity independent of efficacy

Q19. Which experimental precaution is critical when interpreting data from anesthetized animal cardiovascular studies of autonomic drugs?

• Anesthesia does not affect autonomic tone
• Choose an anesthetic that minimally interferes with autonomic receptors and reflexes
• Only use high doses of test compounds to overcome anesthesia effects
• Ignore baseline variability because it is negligible

Correct Answer: Choose an anesthetic that minimally interferes with autonomic receptors and reflexes

Q20. Which statement best describes why multiple species and preparations are used in preclinical autonomic screening?

• To increase experimental complexity without adding predictive value
• To capture species differences in receptor pharmacology, metabolism, and reflex integration that impact translational prediction
• Because regulatory agencies require at least five species for screening
• To ensure every preparation gives the same potency estimate

Correct Answer: To capture species differences in receptor pharmacology, metabolism, and reflex integration that impact translational prediction

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