Which of the following explains why indirect-acting sympathomimetics like amphetamine lose their efficacy with repeated dosing (tachyphylaxis)?
- A Downregulation of adrenergic receptors
- B Induction of monoamine oxidase enzyme
- C Progressive depletion of neuronal norepinephrine stores ✓
- D Increased reuptake transporter expression
Correct answer: C. Progressive depletion of neuronal norepinephrine stores
Explanation
Indirect sympathomimetics act by entering the nerve terminal via the norepinephrine transporter (NET) and displacing stored catecholamines from vesicles. With repeated dosing, the releasable pool of norepinephrine becomes progressively depleted, so each subsequent dose releases less transmitter, resulting in tachyphylaxis. This mechanism is distinct from receptor downregulation, which occurs with direct agonists during prolonged exposure.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.