Which pharmacological agent will NOT cause dilation in a patient with pre-ganglionic Horner's syndrome?

• A. 1% Apraclonidine
• B. Cocaine
• C. 1% Hydroxyamphetamine
• D. Phenylephrine

Answer: (B)

In preganglionic Horner's syndrome, the signal from the brain to the superior cervical ganglion is interrupted, so the postganglionic neurons to the iris dilator are chronically low in norepinephrine. Pharmacologic tests exploit how the iris dilator responds to different agents depending on the integrity of the postganglionic pathway.

Cocaine relies on blocking norepinephrine reuptake at the nerve ending, which requires adequate NE in the synapse to produce dilation. Because there is little norepinephrine available when the preganglionic input is disrupted, cocaine will not cause the affected pupil to dilate.

Apraclonidine works via denervation supersensitivity of the dilator muscle’s alpha-1 receptors in Horner’s; even with reduced NE release, the postganglionic eye becomes more responsive, so the pupil dilates.

Hydroxyamphetamine causes release of stored norepinephrine from intact postganglionic terminals. In a preganglionic lesion, the postganglionic neurons are still present and capable of releasing NE, leading to dilation of the affected pupil.

Phenylephrine is a direct alpha-1 agonist. The denervated eye becomes hypersensitive to such stimulation, so the pupil dilates more readily.

So the agent that will NOT cause dilation in preganglionic Horner's is cocaine.