Screening models for ANS activity – sympathomimetics are essential for B.Pharm students to evaluate drug effects on the autonomic nervous system. This introduction covers key screening approaches: isolated tissue preparations (rabbit aorta, rat vas deferens, guinea-pig trachea), in vivo blood pressure and heart rate assays, electrical field stimulation (EFS), and biochemical tests to distinguish direct versus indirect sympathomimetics. Emphasis is on receptor selectivity (α-adrenergic, β-adrenergic), use of antagonists (phentolamine, propranolol), uptake inhibitors, dose–response curves, and pharmacological parameters (EC50, pA2). Mastery of these models helps interpret agonist/antagonist actions and design reliable bioassays. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which isolated tissue is most commonly used to assess α1-adrenergic vasoconstrictor activity in screening sympathomimetics?
- Guinea-pig ileum
- Rat vas deferens
- Rabbit aorta
- Langendorff-perfused heart
Correct Answer: Rabbit aorta
Q2. Which model is particularly useful to evaluate β2-adrenergic bronchodilator activity?
- Guinea-pig tracheal smooth muscle
- Rabbit aorta strip
- Rat vas deferens
- Frog rectus abdominis
Correct Answer: Guinea-pig tracheal smooth muscle
Q3. Electrical field stimulation (EFS) in isolated tissue preparations is used to:
- Directly activate postsynaptic receptors without neurotransmitter release
- Induce nerve terminal release of endogenous neurotransmitters
- Measure passive diffusion of drugs across membranes
- Quantify receptor density by radioligand binding
Correct Answer: Induce nerve terminal release of endogenous neurotransmitters
Q4. Which agent is used to distinguish α-adrenergic from β-adrenergic mediated responses in functional assays?
- Atropine
- Phentolamine
- Hexamethonium
- Reserpine
Correct Answer: Phentolamine
Q5. A drug that increases heart rate and contractility primarily via β1-adrenoceptors is best screened using:
- Isolated rabbit aorta
- Langendorff-perfused heart or isolated atria
- Guinea-pig ileum contraction assay
- Rat vas deferens EFS
Correct Answer: Langendorff-perfused heart or isolated atria
Q6. How does reserpine pretreatment help distinguish direct from indirect sympathomimetics?
- It increases receptor sensitivity to direct agonists
- It depletes vesicular NE, reducing effects of indirect releasers
- It blocks postsynaptic receptors selectively
- It inhibits monoamine oxidase (MAO) activity
Correct Answer: It depletes vesicular NE, reducing effects of indirect releasers
Q7. Tyramine produces pressor responses by which primary mechanism?
- Direct activation of β2 receptors
- Competitive antagonism at α receptors
- Displacing NE from storage vesicles (indirect release)
- Inhibiting catecholamine synthesis
Correct Answer: Displacing NE from storage vesicles (indirect release)
Q8. In a dose–response curve, EC50 represents:
- The maximum effect achievable by a drug
- The dose required to produce 50% of maximum response
- The concentration of antagonist that halves receptor number
- The time to reach half-maximal effect
Correct Answer: The dose required to produce 50% of maximum response
Q9. Which antagonist would you use to confirm β-adrenergic mediation of an observed relaxation in tracheal smooth muscle?
- Prazosin
- Phentolamine
- Propranolol
- Atropine
Correct Answer: Propranolol
Q10. The rat vas deferens preparation is commonly used to study:
- Cardiac β1 responses only
- Adrenergic neurotransmission and both α and purinergic components
- Cholinergic smooth muscle contraction exclusively
- Endothelial-dependent vasodilation mechanisms
Correct Answer: Adrenergic neurotransmission and both α and purinergic components
Q11. Which experimental treatment would reduce the effect of a releasing agent like tyramine?
- Inhibition of monoamine oxidase (MAO)
- Blockade of neuronal uptake by desipramine
- Pretreatment with reserpine
- Administration of propranolol
Correct Answer: Pretreatment with reserpine
Q12. A competitive antagonist produces which characteristic in a Schild plot?
- A Schild slope of approximately 1 and parallel rightward shift of agonist curves
- An irreversible downward shift of maximal response
- A non-parallel depression of the agonist curve with slope >1
- No change in agonist potency but reduced efficacy
Correct Answer: A Schild slope of approximately 1 and parallel rightward shift of agonist curves
Q13. Which assay can rapidly indicate whether a sympathomimetic is direct-acting at receptors?
- Response remaining after reserpine treatment
- Loss of effect after MAO inhibition
- Enhanced effect when neuronal uptake is blocked
- Reduced response following atropine
Correct Answer: Response remaining after reserpine treatment
Q14. In vitro blockade of the neuronal sodium channel with tetrodotoxin (TTX) during EFS will:
- Increase neurotransmitter release
- Prevent nerve-evoked contractions by blocking action potentials
- Selectively block postsynaptic α receptors
- Enhance indirect sympathomimetic effects
Correct Answer: Prevent nerve-evoked contractions by blocking action potentials
Q15. Which measurement differentiates potency from efficacy in sympathomimetic screening?
- Potency = maximal response; Efficacy = EC50
- Potency = EC50 (or pEC50); Efficacy = maximal response (Emax)
- Both potency and efficacy are identical measures
- Potency = pA2; Efficacy = Schild slope
Correct Answer: Potency = EC50 (or pEC50); Efficacy = maximal response (Emax)
Q16. Which experimental manipulation helps identify involvement of neuronal uptake (Uptake1) in sympathomimetic action?
- Use of atropine to block muscarinic receptors
- Use of desipramine or cocaine to inhibit norepinephrine uptake
- Pretreatment with prazosin to block α1 receptors
- Removal of endothelium from aortic rings
Correct Answer: Use of desipramine or cocaine to inhibit norepinephrine uptake
Q17. A drug that produces vasoconstriction and is blocked by prazosin is likely acting at which receptor subtype?
- β2-adrenoceptor
- α1-adrenoceptor
- β1-adrenoceptor
- α2-adrenoceptor
Correct Answer: α1-adrenoceptor
Q18. Which in vivo assay is commonly used to measure systemic sympathomimetic pressor activity?
- Anesthetized rat or rabbit blood pressure recording (pressor response)
- Isolated guinea-pig ileum contraction assay
- Perfused isolated kidney secretion test
- In vitro radioligand binding to β receptors
Correct Answer: Anesthetized rat or rabbit blood pressure recording (pressor response)
Q19. During screening, a compound increases contractile response in rat vas deferens but is abolished after propranolol. This suggests:
- Action mainly via β-adrenoceptors
- Action mainly via α-adrenoceptors
- Non-adrenergic, cholinergic action
- Action due to direct muscle toxicity
Correct Answer: Action mainly via β-adrenoceptors
Q20. Radioligand binding assays complement functional screening by providing information on:
- Catecholamine release from nerves
- Receptor affinity and number (Bmax and Kd)
- In vivo blood pressure changes
- Rate of neurotransmitter reuptake
Correct Answer: Receptor affinity and number (Bmax and Kd)
Q21. A molecule that is a partial agonist at β receptors will show which characteristic in dose–response assays?
- Produce full Emax equal to a full agonist
- Produce lower maximal effect than a full agonist despite occupying receptors
- Act as an irreversible antagonist
- Only produce effects in presence of an antagonist
Correct Answer: Produce lower maximal effect than a full agonist despite occupying receptors
Q22. Exposure of isolated tissues to monoamine oxidase (MAO) inhibitors will most likely:
- Enhance effects of indirect sympathomimetics that require intracellular metabolism
- Completely block direct α-agonist responses
- Decrease receptor affinity for agonists
- Prevent EFS-evoked neurotransmitter release
Correct Answer: Enhance effects of indirect sympathomimetics that require intracellular metabolism
Q23. Which agent would you use to selectively block presynaptic α2 receptors to examine autoreceptor involvement?
- Yohimbine
- Prazosin
- Propranolol
- Atropine
Correct Answer: Yohimbine
Q24. In a bioassay, a rightward parallel shift of the agonist curve without change in Emax after antagonist addition indicates:
- Non-competitive antagonism
- Competitive (surmountable) antagonism
- Irreversible receptor blockade
- Agonist degradation over time
Correct Answer: Competitive (surmountable) antagonism
Q25. Which tissue preparation is useful to detect both adrenergic contraction and purinergic components, often separated pharmacologically?
- Langendorff heart
- Rat vas deferens
- Rabbit aorta endothelium-intact ring
- Guinea-pig ileum longitudinal muscle
Correct Answer: Rat vas deferens
Q26. A test compound shows reduced effect when neuronal uptake is blocked by cocaine. This observation suggests the compound is likely:
- A direct receptor agonist
- An indirect sympathomimetic requiring uptake into nerve terminals
- A β2-selective agonist acting directly on smooth muscle
- An irreversible antagonist
Correct Answer: An indirect sympathomimetic requiring uptake into nerve terminals
Q27. Which parameter estimates antagonist potency from functional assays and is defined as the negative log of the antagonist concentration producing a twofold shift in agonist EC50?
- pEC50
- pA2
- IC50
- Kd
Correct Answer: pA2
Q28. To pharmacologically isolate β-adrenergic effects in vascular preparations, which combination is commonly used?
- Atropine + hexamethonium
- Propranolol + phentolamine
- Phentolamine to block α receptors and then test β-mediated relaxation
- Yohimbine + prazosin
Correct Answer: Phentolamine to block α receptors and then test β-mediated relaxation
Q29. Which outcome indicates a sympathomimetic is a direct β-agonist during in vitro screening?
- Effect abolished by reserpine
- Effect persists after reserpine and is blocked by propranolol
- Effect increased by uptake inhibitors
- Effect reduced by MAO inhibitors
Correct Answer: Effect persists after reserpine and is blocked by propranolol
Q30. When designing screening protocols for ANS sympathomimetic activity, which strategy improves mechanistic interpretation?
- Use a single tissue and avoid antagonist challenges
- Combine multiple tissues, receptor-selective antagonists, uptake/MAO manipulations, and EFS to differentiate direct vs indirect actions
- Rely solely on in vivo blood pressure changes without in vitro follow-up
- Avoid reserpine or uptake inhibitors because they complicate results
Correct Answer: Combine multiple tissues, receptor-selective antagonists, uptake/MAO manipulations, and EFS to differentiate direct vs indirect actions
