Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/10/25 16:37:12」(JST)

wiki en

3,4-Diaminopyridine (or 3,4-DAP) is an organic compound with the formula C₅H₃N(NH₂)₂. It is formally derived from pyridine by substitution of the 3 and 4 positions with an amino group.

With the International Nonproprietary Name amifampridine, it is used as a drug, predominantly in the treatment of a number of rare muscle diseases. In Europe, the phosphate salt of amifampridine has been licenced as Firdapse (BioMarin Pharmaceutical) in 2010 as an orphan drug.^[3]

Uses[edit]

Although not approved for pharmaceutical use in the United States, 3,4-diaminopyridine is available under compassionate use regulations for the treatment of Lambert-Eaton myasthenic syndrome (LEMS). In Lambert-Eaton syndrome, acetylcholine release is inhibited as antibodies meant to target characteristic cancers target Ca²⁺ channels on the prejunctional membrane instead. 3,4-Diaminopyridine works by blocking potassium channel efflux in nerve terminals so that action potential duration is increased. Ca²⁺ channels can then be open for a longer time and allow greater acetylcholine release to stimulate muscle at the end plate. A 2005 systematic review from the Cochrane Collaboration found some data favouring its use in LEMS.^[4]

It is also used to treat many of the congenital myasthenic syndromes, particularly those with defects in choline acetyltransferase, downstream kinase 7, and those where any kind of defect causes "fast channel" behaviour of the acetylcholine receptor.^[5]

3,4-Diaminopyridine has also been proposed for the treatment of multiple sclerosis, but a 2002 systematic review found that there was little unbiased data to support its use in MS.^[6]

Cost[edit]

The licensing of 3,4-diaminopyridine in 2010 led to a sharp increase in price for the drug. In some cases, this has led to hospitals using an unlicenced form rather than the licensed agent, as the price difference proved prohibitive. BioMarin has been criticised for licencing the drug on the basis of previously conducted research, and yet charging exorbitantly for it.^[7] A group of UK neurologists and pediatricians have petitioned to prime minister David Cameron in an open letter to review the situation.^[8] The company has responded that it submitted the licensing request at the suggestion of the French government, and points out that the increased cost of a licensed drug also means that it is monitored by regulatory authorities (e.g. for uncommon side-effects), a process that was previously not present.^[9] In 2010, company scientists published evidence that amifampridine should be the first-line treatment for LEMS.^[10]

References[edit]

^ AAEM Quality Assurance Committee. American Association of Electrodiagnostic Medicine. (2001). "Practice parameter for repetitive nerve stimulation and single fiber EMG evaluation of adults with suspected myasthena gravis or Lambert-Eaton myasthenic syndrome: summary statement". Muscle Nerve 24 (9): 1236–1238. doi:10.1002/mus.1139. PMID 11494280.
^ Lundh H, Nilsson O, Rosen I, Johansson S. (1993). "Practical aspects of 3,4-diaminopyridine treatment of the Lambert-Eaton myasthenic syndrome". Acta Neurol Scand 88 (2): 136–140. doi:10.1111/j.1600-0404.1993.tb04205.x. PMID 8213058.
^ "Firdapse". European Medicines Agency. Retrieved 2010-09-28.
^ Maddison, P.; Newsom-Davis, J. (2003). "Treatment for Lambert-Eaton myasthenic syndrome". Cochrane Database of Systematic Reviews (CD003279). doi:10.1002/14651858.CD003279. edit
^ Argov, Z. (2009). "Management of myasthenic conditions: nonimmune issues". Current Opinion in Neurology 22: 493. doi:10.1097/WCO.0b013e32832f15fa. edit
^ Solari, A.; Uitdehaag, B. M.; Giuliani, G.; Pucci, E.; Taus, C.; Solari, A. (2002). Aminopyridines for symptomatic treatment in multiple sclerosis. In Solari, Alessandra. "Cochrane Database of Systematic Reviews". Cochrane database of systematic reviews (Online) (4): CD001330. doi:10.1002/14651858.CD001330. PMID 11687106. edit
^ Daniel Martin (2010-09-27). "Hospitals are forced to use unlicensed medicines to save millions". Daily Mail. Archived from the original on 28 September 2010. Retrieved 2010-09-28.
^ Nicholl DJ, Hilton-Jones D, Palace J et al. (2010). "Open letter to prime minister David Cameron and health secretary Andrew Lansley". BMJ 341: c6466. doi:10.1136/bmj.c6466. PMID 21081599.
^ Hawkes N, Cohen D (2010). "What makes an orphan drug?". BMJ 341: c6459. doi:10.1136/bmj.c6459. PMID 21081607.
^ Quartel A, Turbeville S, Lounsbury D (June 2010). "Current therapy for Lambert-Eaton myasthenic syndrome: development of 3,4-diaminopyridine phosphate salt as first-line symptomatic treatment". Curr Med Res Opin 26 (6): 1363–75. doi:10.1185/03007991003745209. PMID 20377318.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. Lambert-Eaton筋無力症候群の治療 treatment of lambert eaton myasthenic syndrome
2. 末梢神経と筋肉に影響を与える腫瘍随伴性症候群 paraneoplastic syndromes affecting peripheral nerve and muscle
3. 神経系の腫瘍随伴性症候群の概要 overview of paraneoplastic syndromes of the nervous system

English Journal

Role of calcium-activated potassium channels in the genesis of 3,4-diaminopyridine-induced periodic contractions in isolated canine coronary artery smooth muscles.

Uchida Y, Maezawa Y, Maezawa Y, Uchida Y, Nakamura F.SourceJapan Foundation for Cardiovascular Research, 2-30-17, Funabashi, Japan, 274-0063. uchiy@ta2.so-net.ne.jp.
The Journal of pharmacology and experimental therapeutics.J Pharmacol Exp Ther.2011 Sep;338(3):974-83. Epub 2011 Jun 16.
We found that 3,4-diaminopyridine (3,4-DAP), a voltage-gated potassium channel (K(V)) inhibitor, elicits pH-sensitive periodic contractions (PCs) of coronary smooth muscles. Underlying mechanisms of PCs, however, remained to be elucidated. The present study was performed to examine the roles of ion
PMID 21680887

Aminopyridines correct early dysfunction and delay neurodegeneration in a mouse model of spinocerebellar ataxia type 1.

Hourez R, Servais L, Orduz D, Gall D, Millard I, de Kerchove d'Exaerde A, Cheron G, Orr HT, Pandolfo M, Schiffmann SN.SourceLaboratory of Neurophysiology and Laboratory of Experimental Neurology, Universite Libre de Bruxelles, 1070 Brussels, Belgium, Laboratory of Electrophysiology, Universite de Mons-Hainaut, 7000 Mons, Belgium, and Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota 55455.
The Journal of neuroscience : the official journal of the Society for Neuroscience.J Neurosci.2011 Aug 17;31(33):11795-807.
The contribution of neuronal dysfunction to neurodegeneration is studied in a mouse model of spinocerebellar ataxia type 1 (SCA1) displaying impaired motor performance ahead of loss or atrophy of cerebellar Purkinje cells. Presymptomatic SCA1 mice show a reduction in the firing rate of Purkinje cell
PMID 21849540

Japanese Journal

P2-220 Lambert-Eaton筋無力症候群治療薬3,4-diaminopyridine服用患者における体内動態と薬効に関する検討(一般演題ポスター発表,薬物動態・TDM・投与設計,臨床から学び臨床へと還元する医療薬学)

石田奈津子,松下良,近藤裕也,小林恵里奈,村上和正,石田千穂,駒井清暢
日本医療薬学会年会講演要旨集 20, 426, 2010-10-25
NAID 110008109219

肺扁平上皮癌に合併した抗P/Q型 voltage-gated calcium channel 抗体陽性の Lambert-Eaton 症候群の1例

片田栄一,中村友彦,渡邊宏久,松川則之,小鹿幸生,祖父江元
臨床神経学 50(1), 17-19, 2010-01-01
NAID 10026291328

Related Pictures

★リンクテーブル★

リンク元	「3,4-ジアミノピリジン」

「3,4-ジアミノピリジン」

3,4-Diaminopyridine
Systematic (IUPAC) name
	3,4-Diaminopyridine
Clinical data
Pregnancy cat.	?
Legal status	Phase III
Routes	Oral
Pharmacokinetic data
Bioavailability	30%,
Identifiers
CAS number	54-96-6
ATC code	N07XX05
PubChem	CID 5918
ChemSpider	5705
UNII	RU4S6E2G0J
ChEMBL	CHEMBL354077
Chemical data
Formula	C5H7N3
Mol. mass	109.13
	SMILES c1cncc(c1N)N;
	InChI InChI=1S/C5H7N3/c6-4-1-2-8-3-5(4)7/h1-3H,7H2,(H2,6,8) ; Key:OYTKINVCDFNREN-UHFFFAOYSA-N ;
(what is this?) (verify);

　　[★]

英: 3,4-diaminopyridine, 3,4-DAP

K+チャネル阻害薬;ランバート・イートン筋無力症治療

[1] AAEM Quality Assurance Committee. American Association of Electrodiagnostic Medicine. (2001). "Practice parameter for repetitive nerve stimulation and single fiber EMG evaluation of adults with suspected myasthena gravis or Lambert-Eaton myasthenic syndrome: summary statement". Muscle Nerve 24 (9): 1236–1238. doi:10.1002/mus.1139. PMID 11494280.

[2] Lundh H, Nilsson O, Rosen I, Johansson S. (1993). "Practical aspects of 3,4-diaminopyridine treatment of the Lambert-Eaton myasthenic syndrome". Acta Neurol Scand 88 (2): 136–140. doi:10.1111/j.1600-0404.1993.tb04205.x. PMID 8213058.

[3] "Firdapse". European Medicines Agency. Retrieved 2010-09-28.

[4] Maddison, P.; Newsom-Davis, J. (2003). "Treatment for Lambert-Eaton myasthenic syndrome". Cochrane Database of Systematic Reviews (CD003279). doi:10.1002/14651858.CD003279. edit

[5] Argov, Z. (2009). "Management of myasthenic conditions: nonimmune issues". Current Opinion in Neurology 22: 493. doi:10.1097/WCO.0b013e32832f15fa. edit

[6] Solari, A.; Uitdehaag, B. M.; Giuliani, G.; Pucci, E.; Taus, C.; Solari, A. (2002). Aminopyridines for symptomatic treatment in multiple sclerosis. In Solari, Alessandra. "Cochrane Database of Systematic Reviews". Cochrane database of systematic reviews (Online) (4): CD001330. doi:10.1002/14651858.CD001330. PMID 11687106. edit

[7] Daniel Martin (2010-09-27). "Hospitals are forced to use unlicensed medicines to save millions". Daily Mail. Archived from the original on 28 September 2010. Retrieved 2010-09-28.

[Nichol-8] Nicholl DJ, Hilton-Jones D, Palace J et al. (2010). "Open letter to prime minister David Cameron and health secretary Andrew Lansley". BMJ 341: c6466. doi:10.1136/bmj.c6466. PMID 21081599.

[9] Hawkes N, Cohen D (2010). "What makes an orphan drug?". BMJ 341: c6459. doi:10.1136/bmj.c6459. PMID 21081607.

[10] Quartel A, Turbeville S, Lounsbury D (June 2010). "Current therapy for Lambert-Eaton myasthenic syndrome: development of 3,4-diaminopyridine phosphate salt as first-line symptomatic treatment". Curr Med Res Opin 26 (6): 1363–75. doi:10.1185/03007991003745209. PMID 20377318.

匿名

検索

案内

案内

3,4-diaminopyridine