A pharmacologist studies a drug that activates presynaptic alpha-2 adrenoceptors at sympathetic nerve terminals in the heart. The expected net effect of this drug would be:

• A Increased norepinephrine release leading to tachycardia
• B Stimulation of beta-1 receptors in the SA node
• C Blockade of muscarinic M2 receptors in the atria
• D Decreased norepinephrine release leading to reduced heart rate ✓

Explanation

Presynaptic alpha-2 receptors act as autoreceptors that inhibit further norepinephrine release when activated — a negative feedback mechanism. Stimulating these receptors reduces norepinephrine in the synaptic cleft, thereby lowering heart rate and inotropy. This is the basis for drugs like clonidine causing bradycardia through this central and peripheral mechanism.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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