In Horner's syndrome, the hydroxyamphetamine (paredrine) test distinguishes central/preganglionic from postganglionic lesions. The pharmacological basis is:

• A Hydroxyamphetamine stimulates alpha-1 receptors directly, bypassing the need for intact nerve terminals
• B Hydroxyamphetamine acts indirectly by releasing stored norepinephrine from intact third-order (postganglionic) neuron terminals; absent pupil dilation indicates third-order neuron damage ✓
• C It inhibits monoamine oxidase, allowing accumulated norepinephrine to stimulate the dilator in all types of Horner's
• D It blocks acetylcholinesterase, facilitating sphincter relaxation and mimicking sympathetic dominance

Explanation

Hydroxyamphetamine (1% paredrine) releases pre-stored norepinephrine from intact postganglionic (third-order) neuron terminals. If the third-order neuron is intact (i.e., central or preganglionic/second-order Horner's), the Horner pupil will dilate (often to equal size as the normal pupil) because viable terminals release NE. If the third-order neuron is damaged (postganglionic Horner's), there are no functional terminals to release NE, so the Horner pupil fails to dilate — confirming a postganglionic lesion. This distinction is clinically important: postganglionic Horner's (from C8-T1 Pancoast tumor, carotid dissection) has a different differential diagnosis from central Horner's.

Reference: Khurana Comprehensive Ophthalmology, 7th ed.

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Written and medically reviewed by the StethoPrep medical team.