4-Aminopyridine

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4-Aminopyridine

IUPAC name	pyridin-4-amine
Other names	4-pyridinamine, 4-Pyridylamine, Fampridine
Identifiers
CAS number	[504-24-5]
PubChem	1727
MeSH	4-Aminopyridine
SMILES	C1=CN=CC=C1N
Properties
Molecular formula	C₅H₆N₂
Molar mass	94.1146
Appearance	colourless solid
Melting point	155-158 °C
Boiling point	273 °C
Solubility in water	polar organic solvents
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references

4-Aminopyridine is an organic compound with the formula H₂NC₅H₄N. The molecule is one of the three isomeric amines of pyridine. It is used primarily as a research tool and is helpful in characterizing subtypes of potassium channel.

1 Production
2 Pharmaceutical applications
3 Multiple Sclerosis
4 Overdose
5 See also
6 References
7 External links

[edit] Production

4-Aminopyridine is prepared by the decarbonylation of pyridine-4-carboxyamide.^[1]

[edit] Pharmaceutical applications

It has been used clinically in Lambert-Eaton myasthenic syndrome and multiple sclerosis because by blocking potassium channels it prolongs action potentials thereby increasing transmitter release at the neuromuscular junction and elsewhere.^[2] The drug Pinacidil is a derivative of 4-aminopyridine that is also used as a potassium channel opener.

The drug, known as Neurelan, has been shown to reverse tetrodotoxin toxicity in animal experiments.^[3]

It is also marketed as Fampridine by Acorda for the treatment of multiple sclerosis, for which it is now in Phase II clinical trials.

4-Aminopyridine is marketed as an avicide under the trade name Avitrol. In this treatment it causes convulsions and rarely death, depending on dosage.

[edit] Multiple Sclerosis

4-Aminopyridine (4-AP) is a drug shown to improve visual function and motor skills and relieve fatigue in patients with Multiple Sclerosis (MS). 4-AP is most effective in patients with the chronic progressive form of MS, in patients who are temperature sensitive, and in patients who have had MS for longer than three years. Common side effects include dizziness, nervousness and nausea, and the incidence of adverse effects was shown to be less than 5% in all studies.

4-AP works as a potassium channel blocker. Electrophysiologic studies of demyelinated axons show that abnormal potassium currents decrease action potential duration and amplitude and contribute to conduction failure. Potassium channel blockade prolongs the depolarization phase of the action potential, increasing conductivity along the demyelinated axon.

MS patients treated with 4-AP exhibited a response rate of 29.5% to 80%. A long-term study (32 months) indicated that 80-90% of patients who initially responded to 4-AP exhibited long-term benefits. Although improving symptoms, 4-AP does not inhibit progression of MS.

Spinal cord injury patients have also seen improvement with 4-AP therapy. These improvements include sensory, motor and pulmonary function, with a decrease in spasticity and pain.^[4].

[edit] Overdose

Conditions associated with overdose have included parasthesias and seizures.^[5], and atrial fibrillation.^[6]

[edit] See also

[edit] References

^ Shinkichi Shimizu, Nanao Watanabe, Toshiaki Kataoka, Takayuki Shoji, Nobuyuki Abe, Sinji Morishita, Hisao Ichimura "Pyridine and Pyridine Derivatives" in "Ullmann's Encyclopedia of Industrial Chemistry" 2007; John Wiley & Sons: New York.
^ Judge S, Bever C (2006). "Potassium channel blockers in multiple sclerosis: neuronal Kv channels and effects of symptomatic treatment". Pharmacol. Ther. 111 (1): 224–59. doi:10.1016/j.pharmthera.2005.10.006. PMID 16472864.
^ Octopus Envenomations at eMedicine.com
^ Van Diemen HA, Polman CH, Koetsier JC, Van Loenen AC, Nauta JJ, Bertelsmann FW (1993). "4-Aminopyridine in patients with multiple sclerosis: dosage and serum level related to efficacy and safety". Clinical Neuropharmacology 16 (3): 195–204. PMID 8504436.
^ Pickett T, Enns R (1996). "Atypical presentation of 4-aminopyridine overdose". Annals of emergency medicine 27 (3): 382–5. doi:10.1016/S0196-0644(96)70277-9. PMID 8599505.
^ Johnson N, Morgan M (2006). "An unusual case of 4-aminopyridine toxicity". The Journal of emergency medicine 30 (2): 175–7. doi:10.1016/j.jemermed.2005.04.020. PMID 16567254.