Which of the following best explains why indirect sympathomimetics like amphetamine lose efficacy with repeated dosing (tachyphylaxis)?

• A Depletion of releasable norepinephrine from vesicular stores ✓
• B Downregulation of postsynaptic beta receptors
• C Competitive inhibition of monoamine oxidase
• D Upregulation of catechol-O-methyltransferase activity

Explanation

Indirect sympathomimetics act by releasing norepinephrine from the nerve terminal vesicles rather than directly activating receptors. With repeated administration, the readily releasable pool of vesicular norepinephrine is depleted faster than it can be resynthesized, leading to progressively diminishing responses — a phenomenon called tachyphylaxis. Direct agonists, by contrast, do not deplete vesicular stores and show less tachyphylaxis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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