**Core Concept**
The weaning-off effect in long-term levodopa therapy refers to the diminished response to levodopa due to dopamine receptor downregulation and loss of dopaminergic neuron function. This leads to motor fluctuations and "wearing-off" phenomena. To restore motor function, a COMT inhibitor is required to prolong levodopa’s duration of action and enhance its bioavailability.

**Why the Correct Answer is Right**
Tolcapone is a central catechol-O-methyltransferase (COMT) inhibitor that prevents the degradation of levodopa in the brain. By inhibiting COMT, tolcapone increases the half-life and bioavailability of levodopa, thereby enhancing its effect and reducing motor fluctuations. It is particularly effective in patients with long-term levodopa use and is approved for use in advanced Parkinson’s disease with motor fluctuations.

**Why Each Wrong Option is Incorrect**
Option B: Amantadine is a dopamine agonist and antiviral agent; it has limited efficacy in reversing weaning-off and is not a COMT inhibitor.
Option C: Rasagiline is a monoamine oxidase-B (MAO-B) inhibitor, which may slow dopamine breakdown but is not effective in reversing weaning-off due to its slow onset and limited impact on levodopa metabolism.
Option D: Benzhexol is a dopamine agonist used in early Parkinson’s, not for reversing weaning-off in long-term levodopa users.

**Clinical Pearl / High-Yield Fact**
In patients on long-term carbidopa-levodopa therapy, adding a COMT inhibitor like tolcapone or entacapone is first-line for managing motor fluctuations. Avoid using dopamine agonists in this setting as they may worsen dyskinesias.

✓ Correct Answer: A. Tolcapone