Which of the following correctly describes the mechanism by which indirect-acting sympathomimetics like amphetamine increase norepinephrine at the synapse?
- A Direct agonism at alpha and beta adrenoceptors
- B Inhibition of monoamine oxidase at the synaptic cleft
- C Carrier-mediated reverse transport of norepinephrine from vesicles and the cytoplasm ✓
- D Blockade of neuronal reuptake transporter NET only
Correct answer: C. Carrier-mediated reverse transport of norepinephrine from vesicles and the cytoplasm
Explanation
Amphetamine enters the nerve terminal via the norepinephrine transporter (NET), then enters vesicles via VMAT, displacing norepinephrine into the cytoplasm. It also reverses NET direction, pumping norepinephrine out of the neuron into the synapse — a carrier-mediated non-exocytotic release. This mechanism is independent of action potentials and is not blocked by cocaine (which only blocks reuptake without reversing transport).
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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