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4-aminopyridine (4-AP)

Timothy C. Hain, MD

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4-aminopyridine is a new medication that may be useful in treating dizziness associated with cerebellar disorders. It is related to 3,4 Diaminopyridine (3-4 DAP) which acts to a greater extent on outside the brain than 4-AP. 4-AP is preferred to 3-4 DAP for central nervous system conditions, presumably because it gets into the brain to a greater extent (Kalla et al, 2011)

Availability

4-AP is a prescription medication. There are several ways of getting 4-AP. If you have multiple sclerosis, or if you are very wealthy, you can get 4-AP under the brand name of "Ampyra". Ampyra is a 10 mg time-release preparation of 4-AP. If you do not have MS, as there is no other FDA approved indication, your insurance company will likely not cover Ampyra, leaving you to pay out of your pocket (and it is very expensive).

Otherwise, you can usually obtain 4-AP, for relatively ordinary prices, even in a time release format, from a compounding pharmacy. This is because the chemical 4-AP is not expensive.

Rationale for use of 4-AP:

4-AP is a potassium channel blocker that works both on nerves and the central nervous system (Leigh, 2003) . 4-AP affects cerebellar metabolism (Bense, 2006). Some authors suggest that it increases the excitability of the cerebellar Purkinje cells (Glasauer et al, 2005).

Reports of the effect of 4-AP on central disorders

Cerebellar disorders.

4-AP has been reported to improve patients with EA-2 (Lohle et al, 2008; Spacey, 1993; ; Strupp 2007; Strupp 2011)

4-AP has also been reported to improve oculomotor and vestibular function in ataxia telangiectasia (Shaikh et al, 2013), including periodic alternating nystagmus (PAN).

There are also other miscellaneous reports of improvement in various cases.

downbeating nystagmus

There have been several studies that report it to be effective for downbeating nystagmus and improves postural stability in persons with downbeating nystagmus (Claassen et al, 2013a,b; Helmchen et al, 2004; Sander et al, 2011; Sprenger et al, 2005, 2006).

4-AP has also been reported in the German literature to improve upbeating nystagmus. (Glasauer et al, 2005). This effect was suggested to be related to improved visual tracking. As the effect was only present in the light, it was suggested that the mechanism was light dependent.

gaze-evoked nystagmus.

Kalla et al (2007) suggested that 4-AP reduces ocular drift leading to nystagmus and that it was a "promising" treatment option for gaze evoked nystagmus.

Positional nystagmus.

Kremmyda (2013) suggested that 4-AP suppressed positional nystagmus associated with a cerebellar vermis lesion.

4-AP does not work in:

Essential tremor (Lorenz et al, 2006).

Side Effects

4-AP can cause dizziness and confusion and stomach upset. It can rarely cause seizures.

It is nearly completely eliminated unchanged in the urine, and thus it has little opportunity to result in drug interactions. In patients with impaired kidney function, levels are higher and it lasts longer (Cornblath et al, 2012).

An overdose of 4-AP ws reported by Schwam (2011). A man developed sudden onset of abdominal pain, vertigo, anxiety, profuse diaphoresis, hypersalivation, hypertension, bradycardia, agitation, and choreoathetosis, followed by status epilepticus. Due to a compounding pharmacy error, he was given pills that contained approximately 10 times the dose indicated on the label.

Suggestions

4-AP is an "emerging" treatment for cerebellar nystagmus and ataxia. We think it is prudent to use relatively low doses -- such as those reported in the literature (10 to 20 mg twice/day), and also to monitor the effects on the eyes and posture. We think a video-recording of downbeating nystagmus (before and after) combined with a posturography study would be a good method of proving that a drug is useful (or not).

Summary:

4-AP has recently been reported to be helpful in treating cerebellar disorders. It is likely that it works by stimulating the cerebellum.

References:

Copyright August 3, 2016 , Timothy C. Hain, M.D. All rights reserved. Last saved on August 3, 2016