プラリドキシム pralidoxime, 2-pyridine aldoxime methiodide

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the 16th letter of the Roman alphabet (同)p

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personal assistant個人秘書 / public address [system]
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phosphorusの化学記号

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/14 17:07:32」(JST)

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Pralidoxime (2-pyridine aldoxime methyl chloride,) or 2-PAM, usually as the chloride or methiodide salts, belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase. It is used to combat poisoning by organophosphates^[1] or acetylcholinesterase inhibitors (nerve agents) in conjunction with atropine and diazepam.

Chemical synthesis

Pralidoxime, 2-pyridinaldoxime methylchloride, is synthesized by reacting picolinaldehyde (2-formyl pyridine) with hydroxylamine, giving pyridine-2-aldoxime, which is further reacted with methyl iodide, giving the desired pralidoxime.^[2]^[3]^[4]^[5]

Mechanism of action

Pralidoxime is typically used in cases of organophosphate poisoning. The acetylcholinesterase enzyme has two parts to it. An acetylcholine molecule, bound at both ends to both sites of the enzyme, is cleaved in two to form acetic acid and choline. In organophosphate poisoning, an organophosphate binds to just one end of the acetylcholinesterase enzyme (the esteric site), blocking its activity. Pralidoxime is able to attach to the other half (the unblocked, anionic site) of the acetylcholinesterase enzyme. It then binds to the organophosphate, the organophosphate changes conformation, and loses its binding to the acetylcholinesterase enzyme. The conjoined poison / antidote then unbinds from the site, and thus regenerates the enzyme, which is now able to function again.

After some time though, some inhibitors can develop a permanent bond with cholinesterase, known as aging, where oximes such as pralidoxime cannot reverse the bond. Pralidoxime is often used with atropine (a muscarinic antagonist) to help reduce the parasympathetic effects of organophosphate poisoning. Pralidoxime is only effective in organophosphate toxicity (i.e. it does not have an effect if the acetylcholinesterase enzyme is carbamylated, as occurs with neostigmine or physostigmine).

Pralidoxime has an important role in reversing paralysis of the respiratory muscles but due to its poor blood–brain barrier penetration, it has little effect on centrally-mediated respiratory depression. This is why atropine, which has excellent blood–brain barrier penetration, is concomitantly administered with pralidoxime during the treatment of organophosphate poisoning. While the efficacy of atropine has been well-established, clinical experience with pralidoxime has led to widespread doubt about its efficacy in treatment of organophosphorus poisoning.^[6]

Dosage

Adults: 30 mg/kg (typically 1-2 g), administered by intravenous therapy over 15–30 minutes or intramuscular injection or subcutaneous injection, repeated 60 minutes later. It can also be given as a 500 mg/h continuous IV infusion.
Children: 20–50 mg/kg followed by a maintenance infusion at 5–10 mg/kg/h.

Intravenous infusions can lead to respiratory or cardiac arrest if given too quickly.^[7]

Interactions

When atropine and pralidoxime are used together, the signs of atropinization (flushing, mydriasis, tachycardia, dryness of the mouth and nose) may occur earlier than might be expected when atropine is used alone. This is especially true if the total dose of atropine has been large and the administration of pralidoxime has been delayed.

The following precautions should be kept in mind in the treatment of anticholinesterase poisoning, although they do not bear directly on the use of pralidoxime: since barbiturates are potentiated by the anticholinesterases, they should be used cautiously in the treatment of convulsions; morphine, theophylline, aminophylline, succinylcholine, reserpine, and phenothiazine-type tranquilizers should be avoided in patients with organophosphate poisoning.

Contraindications

There are no known absolute contraindications for the use of pralidoxime. Relative contraindications include known hypersensitivity to the drug and other situations in which the risk of its use clearly outweighs possible benefit.

References

^ Jokanović M, Prostran M (2009). "Pyridinium oximes as cholinesterase reactivators. Structure-activity relationship and efficacy in the treatment of poisoning with organophosphorus compounds". Curr. Med. Chem. 16 (17): 2177–88. doi:10.2174/092986709788612729. PMID 19519385.
^ D. Nachmansonn, S. Ginsburg, U.S. Patent 2,816,113 (1957)
^ L.P. Black, U.S. Patent 3,123,613 (1964)
^ D.E. Easterday, A.A. Kondritzer, U.S. Patent 3,140,289 (1964)
^ W.B. McDowell, U.S. Patent 3,155,674 (1964)
^ [2]Banerjee I, Tripathi S K, Roy A S. Efficacy of pralidoxime in organophosphorus poisoning: Revisiting the controversy in Indian setting. J Postgrad Med 2014;60:27-30
^ Baxter Healthcare Corporation 2006, Protopam Prescribing Information

External links

Drugs.com

UpToDate Contents

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English Journal

Evaluation of the performance of the OneTouch Select® Plus blood glucose test system against ISO 15197:2013.

Setford S1, Smith A1, McColl D1, Grady M1, Koria K1, Cameron H1.
Expert review of medical devices.Expert Rev Med Devices.2015 Oct 21:1-11. [Epub ahead of print]
OBJECTIVES: Assess laboratory and in-clinic performance of the OneTouch Select® Plus test system against ISO 15197:2013 standard for measurement of blood glucose.METHODS: System performance assessed in laboratory against key patient, environmental and pharmacologic factors. User performance was ass
PMID 26488139

Neuroprotection Against Diisopropylfluorophosphate in Acute Hippocampal Slices.

Ferchmin PA1,2, Pérez D3, Cuadrado BL3, Carrasco M3, Martins AH4, Eterović VA3.
Neurochemical research.Neurochem Res.2015 Oct 5. [Epub ahead of print]
Diisopropylfluorophosphate (DFP) is an irreversible inhibitor of acetylcholine esterase and a surrogate of the organophosphorus (OP) nerve agent sarin. The neurotoxicity of DFP was assessed as a reduction of population spike (PS) area elicited by synaptic stimulation in acute hippocampal slices. Two
PMID 26438150

Monooxime Bispyridinium Reactivators Bearing Xylene Linker - Synthesis and In Vitro Evaluation on Model of Organophosphate-Inhibited Acetylcholinesterase.

Musilek K, Hambalek J, Holas O, Dohnal V, Kuca K1.
Medicinal chemistry (Shariqah (United Arab Emirates)).Med Chem.2015 Oct 2. [Epub ahead of print]
Nine novel mono-oxime reactivators bearing xylene linker were synthesized in effort to improve previously prepared xylene bisoximes and monocarbamoyl-monooximes. The novel compounds were tested in vitro on the model of tabun-, paraoxon-, methylparaoxon- and DFP-inhibited human erythrocyte AChE. Thei
PMID 26427931

Japanese Journal

Multi-Gigabit Pre-Emphasis Design and Analysis for Serial Link(Electronic Circuits)

LIN Chih-Hsien,TSAI Chang-Hsiao,CHEN Chih-Ning,JOU Shyh-Jye
IEICE transactions on electronics E88-C(10), 2009-2019, 2005-10-01
… In this paper, a multi-Gbps pre-emphasis design methodology and circuits for a 4/2 Pulse Amplitude Modulation (PAM) transmitter of high-speed data serial link over cable are proposed. … In order to gain higher data rates without increasing of symbol rate, we use 4 PAM in our system. … The measurement results of 10/5 Gbps (4/2 PAM) are carried out over 5 meter (m) long cable and is in agreement with our analysis and simulation results. …
NAID 110003215097

Relationship between structures and biological activities of mycoplasmal diacylated lipopeptides and their recognition by Toll-like receptors 2 and 6

Okusawa Tsugumi,Fujita Mari,Nakamura Jun-ichiro,Into Takeshi,Yasuda Motoaki,Yoshimura Atsutoshi,Hara Yoshitaka,Hasebe Akira,Golenbock Douglas T.,Morita Manabu,Kuroki Yoshio,Ogawa Tomohiko,Shibata Ken-ichiro
Infection and immunity 72(3), 1657-1665, 2004-03-00
… The lipopeptide FSL-1 [S-(2,3-bispalmitoyloxypropyl)-Cys-Gly-Asp-Pro-Lys-His-Pro-Lys-Ser-Phe,Pam2CGDPKHPKSF] synthesized on the basis of the N-terminal structure of a Mycoplasmasalivarium lipoprotein capable of activating normal human gingival fibroblasts to induce the cellsurface expression of ICAM-1 revealed the activity to induce production of monocytechemoattractant protein-1, IL-6 and IL-8. …
NAID 120002451624

2-PAM/4-PAM backplane transceiver cell

ZERBE J. L.
IEEE J. Solid-State Circuits, 2003
NAID 80016363430

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★リンクテーブル★

リンク元	「プラリドキシム」
関連記事	「PAM」「PA」「P」

「プラリドキシム」

Pralidoxime
Systematic (IUPAC) name
	2-[(hydroxyimino)methyl]-1-methylpyridin-1-ium
Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
Pregnancy; category	C;
Legal status	℞ (Prescription only);
Identifiers
CAS Number	6735-59-7
ATC code	V03AB04
PubChem	CID: 6789253
IUPHAR/BPS	4652
DrugBank	DB00733
ChemSpider	5193737
UNII	P7MU9UTP52
KEGG	C07400
ChEBI	CHEBI:8354
ChEMBL	CHEMBL1420
Synonyms	1-methylpyridine-6-carbaldehyde oxime
Chemical data
Formula	C7H9N2O+
Molecular mass	137.159 g/mol
	SMILES O=[NH+]C=C1\C=C/C=C\N1C ;
	InChI InChI=1S/C7H8N2O/c1-9-5-3-2-4-7(9)6-8-10/h2-6H,1H3/p+1 ; Key:JBKPUQTUERUYQE-UHFFFAOYSA-O ;
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