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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/01 10:52:16」(JST)

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Suramin is an antiparasitic drug developed by Oskar Dressel and Richard Kothe of Bayer, Germany in 1916, and is still sold by Bayer under the brand name Germanin. The formula of suramin was kept secret by Bayer for commercial reasons, however, it was elucidated and published in 1924 by Ernest Fourneau and his team of the Pasteur Institute.^[1]^:378-379^[2]

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.^[3]

Medical uses

Protozoa

It is used for treatment of human sleeping sickness caused by trypanosomes.^[4]

Helminthiasis

It has been used in the treatment of onchocerciasis.^[5]

Adverse reactions

The most frequent adverse reactions are nausea and vomiting. About 90% of patients will get an urticarial rash that disappears in a few days without needing to stop treatment. There is a greater than 50% chance of adrenal cortical damage, but only a smaller proportion will require lifelong corticosteroid replacement. It is common for patients to get a tingling or crawling sensation of the skin with suramin. Suramin will cause clouding of the urine which is harmless: patients should be warned of this to avoid them becoming alarmed.

Kidney damage and exfoliative dermatitis occur less commonly.

Suramin has been applied clinically to HIV/AIDS patients resulting in a significant number of fatal occurrences and as a result the application of this molecule was abandoned for this condition.^[6]

Chemistry

The molecular formula of suramin is C₅₁H₄₀N₆O₂₃S₆. It is a symmetric molecule in the center of which lies a urea (NH–CO–NH) functional group. Suramin contains eight benzene rings, four of which are fused in pairs (naphthalene), four amide groups (in addition to the urea) and six sulfonic acid groups. When given as drug, it is usually as the sodium sulfonate, with six sodium ions on the sulfonate groups rather than hydrogens.

Research

Suramin was studied as a possible treatment for prostate cancer in a clinical trial.^[7]

It has been studied in a mouse model of autism^[8]^[9]^[10]

Suramin is also used in research as a broad-spectrum antagonist of P2 receptors^[11]^[12] and agonist of Ryanodine receptors.^[13]

Its effect on telomerase has been investigated.^[14]

It may have some activity against RNA viruses.^[15]

In addition to antagonism of P2 receptors, Suramin inhibits the activation of heterotrimeric G proteins in a variety of other GPCRs with varying potency. It prevents the association of heteromeric G proteins and therefore the receptors guanine exchange functionality (GEF). With this blockade the GDP will not release from the Gα subunit so it can not be replaced by a GTP and become activated. This has the effect of blocking downstream G protein mediated signaling of various GPCR proteins including rhodopsin, the A1 adenosine receptor, and the D2 dopamine receptor.^[16]

References

^ Walter Sneader. Drug Discovery: A History. John Wiley & Sons, 2005 ISBN 9780471899792
^ Fourneau, E.; Th; Vallée, J. (1924). "Sur une nouvelle série de médicaments trypanocides". C. R. Séances Acad. Sci. 178: 675.
^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
^ Darsaud A, Chevrier C, Bourdon L, Dumas M, Buguet A, Bouteille B (January 2004). "Megazol combined with suramin improves a new diagnosis index of the early meningo-encephalitic phase of experimental African trypanosomiasis". Trop. Med. Int. Health 9 (1): 83–91. doi:10.1046/j.1365-3156.2003.01154.x. PMID 14728611.
^ Anderson J, Fuglsang H (July 1978). "Further studies on the treatment of ocular onchocerciasis with diethylcarbamazine and suramin". Br J Ophthalmol 62 (7): 450–7. doi:10.1136/bjo.62.7.450. PMC 1043255. PMID 678497.
^ "Lack of response to suramin in patients with AIDS and AIDS-related complex." 82. Mar 1987. pp. 615–20. PMID 3548350.
^ Ahles TA, Herndon JE, Small EJ, et al. (November 2004). "Quality of life impact of three different doses of suramin in patients with metastatic hormone-refractory prostate carcinoma: results of Intergroup O159/Cancer and Leukemia Group B 9480". Cancer 101 (10): 2202–8. doi:10.1002/cncr.20655. PMID 15484217.
^ http://medicalxpress.com/news/2013-03-drug-treatment-autism-symptoms-mouse.html
^ http://news.sciencemag.org/biology/2014/06/century-old-drug-reverses-signs-autism-mice
^ http://www.nature.com/tp/journal/v4/n6/full/tp201433a.html
^ Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Knight GE, Fumagalli M, Gachet C, Jacobson KA, Weisman GA. (September 2006). "International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy". Pharmacol Rev. 58 (3): 281–341. doi:10.1124/pr.58.3.3. PMC 3471216. PMID 16968944.
^ Khakh BS, Burnstock G, Kennedy C, King BF, North RA, Séguéla P, Voigt M, Humphrey PP. (March 2001). "International union of pharmacology. XXIV. Current status of the nomenclature and properties of P2X receptors and their subunits". Pharmacol Rev. 53 (1): 107–118. PMID 11171941.
^ Wolner I, Kassack MU, Ullmann H, Karel A, Hohenegger M (October 2005). "Use-dependent inhibition of the skeletal muscle ryanodine receptor by the suramin analogue NF676". Br. J. Pharmacol. 146 (4): 525–33. doi:10.1038/sj.bjp.0706359. PMC 1751178. PMID 16056233.
^ Erguven M, Akev N, Ozdemir A, Karabulut E, Bilir A (August 2008). "The inhibitory effect of suramin on telomerase activity and spheroid growth of C6 glioma cells". Med. Sci. Monit. 14 (8): BR165–73. PMID 18667993.
^ Mastrangelo E, Pezzullo M, Tarantino D, Petazzi R, Germani F, Kramer D, Robel I, Rohayem J, Bolognesi M, Milani M (2012) Structure-based inhibition of norovirus RNA-dependent RNA-polymerases. J Mol Biol
^ Beindl W, Mitterauer T, Hohenegger M, Ijzerman AP, Nanoff C, Freissmuth M. (August 1996). "Inhibition of receptor/G protein coupling by suramin analogues". ol. Pharmacology. 50 (2): 415–23. PMID 8700151.

External links

Suramin bound to proteins in the PDB
Drug information
Suramin, drug information by JBC Online
Suramin in treating patients with recurrent bladder cancer
National Cancer Institute

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. アフリカ・トリパノソーマ症の臨床症状、診断、および治療 clinical manifestations diagnosis and treatment of african trypanosomiasis
2. 抗原虫治療 antiprotozoal therapies
3. 男性における原発性性腺機能低下の原因 causes of primary hypogonadism in males
4. 原発性副腎不全（アジソン病）の原因 causes of primary adrenal insufficiency addisons disease
5. シャルコーマリートゥース病などの一次性の遺伝性運動感覚性ニューロパチー hereditary primary motor sensory neuropathies including charcot marie tooth disease

English Journal

Aerobic exercise training increases nitrergic innervation function and decreases sympathetic innervation function in mesenteric artery from rats fed a high-fat diet.

Sastre E1, Caracuel L, Balfagón G, Blanco-Rivero J.
Journal of hypertension.J Hypertens.2015 Sep;33(9):1819-30. doi: 10.1097/HJH.0000000000000627.
INTRODUCTION: We investigated whether high-fat diet (HFD)-induced obesity was associated with modifications in mesenteric innervation function, the mechanisms involved, and the possible effects of aerobic exercise training on these changes.MATERIALS AND METHODS: Male Wistar rats were divided into th
PMID 26103124

Potentiation of temozolomide antitumor effect by purine receptor ligands able to restrain the in vitro growth of human glioblastoma stem cells.

D'Alimonte I1, Nargi E, Zuccarini M, Lanuti P, Di Iorio P, Giuliani P, Ricci-Vitiani L, Pallini R, Caciagli F, Ciccarelli R.
Purinergic signalling.Purinergic Signal.2015 Sep;11(3):331-346. Epub 2015 May 15.
Glioblastoma multiforme (GBM), the most common and aggressive brain tumor in humans, comprises a population of stem-like cells (GSCs) that are currently investigated as potential target for GBM therapy. Here, we used GSCs isolated from three different GBM surgical specimens to examine the antitumor
PMID 25976165

Suppressing RNA silencing with small molecules and the viral suppressor of RNA silencing protein p19.

Danielson DC1, Filip R2, Powdrill MH2, O'Hara S3, Pezacki JP4.
Biochemical and biophysical research communications.Biochem Biophys Res Commun.2015 Aug 7;463(4):1135-40. doi: 10.1016/j.bbrc.2015.06.071. Epub 2015 Jun 14.
RNA silencing is a gene regulatory and host defense mechanism whereby small RNA molecules are engaged by Argonaute (AGO) proteins, which facilitate gene knockdown of complementary mRNA targets. Small molecule inhibitors of AGO represent a convenient method for reversing this effect and have applicat
PMID 26079891

Japanese Journal

Transforming Growth Factor β1 Alters Calcium Mobilizing Properties and Endogenous ATP Release in A549 Cells: Possible Implications for Cell Migration

Miki Kenji,Tanaka Hiromitsu,Nagai Yoko,Kimura Chiwaka,Oike Masahiro
Journal of Pharmacological Sciences advpub(0), 1007220420, 2010
… ATPγS-induced migration of TGFβ1-treated A549 cells was reversed by the P2 antagonist suramin. …
NAID 130000301216

Modulation of the activity of two pacemakers by transmural nerve stimulation in circular smooth muscle preparations isolated from the rat proximal colon

KATO Takashi,NAKAMURA Eri,IMAEDA Kenro,SUZUKI Hikaru
Journal of smooth muscle research = 日本平滑筋学会機関誌 45(6), 249-268, 2009-12-01
… The former were not antagonized by apamin, guanethidine or suramin, while the latter were antagonized by capsaicin, suggesting an innervation by non-adrenergic non-cholinergic non-nitrergic (NANCNN) inhibitory and peptidergic excitatory nerves, respectively. …
NAID 10025993957

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★リンクテーブル★

リンク元	「駆虫薬」「スラミン」
拡張検索	「suramin sodium」

「駆虫薬」

Suramin
Systematic (IUPAC) name
	8,8'-{Carbonylbis[imino-3,1-phenylenecarbonylimino(4-methyl-3,1-phenylene)carbonylimino]}di(1,3,5-naphthalenetrisulfonic acid)
Clinical data
Trade names	Antrypol, 309 F or 309 Fourneau, Bayer 205, Moranyl, Naganin, Naganine
Legal status	not approved by the US FDA;
Routes of; administration	injection
Identifiers
CAS Number	145-63-1
ATC code	P01CX02 QP51AE02
PubChem	CID: 5361
IUPHAR/BPS	1728
DrugBank	DB04786
ChemSpider	5168
UNII	6032D45BEM
KEGG	C07974
ChEBI	CHEBI:45906
ChEMBL	CHEMBL265502
Chemical data
Formula	C51H40N6O23S6
Molecular mass	1297.29
	SMILES O=C(Nc1cc(ccc1C)C(=O)Nc3c2c(cc(cc2c(cc3)S(=O)(=O)O)S(=O)(=O)O)S(=O)(=O)O)c8cccc(NC(=O)Nc7cc(C(=O)Nc6cc(C(=O)Nc5c4c(cc(cc4c(cc5)S(=O)(=O)O)S(=O)(=O)O)S(=O)(=O)O)ccc6C)ccc7)c8 ;
	InChI InChI=1S/C51H40N6O23S6/c1-25-9-11-29(49(60)54-37-13-15-41(83(69,70)71)35-21-33(81(63,64)65)23-43(45(35)37)85(75,76)77)19-39(25)56-47(58)27-5-3-7-31(17-27)52-51(62)53-32-8-4-6-28(18-32)48(59)57-40-20-30(12-10-26(40)2)50(61)55-38-14-16-42(84(72,73)74)36-22-34(82(66,67)68)24-44(46(36)38)86(78,79)80/h3-24H,1-2H3,(H,54,60)(H,55,61)(H,56,58)(H,57,59)(H2,52,53,62)(H,63,64,65)(H,66,67,68)(H,69,70,71)(H,72,73,74)(H,75,76,77)(H,78,79,80) ; Key:FIAFUQMPZJWCLV-UHFFFAOYSA-N ;
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　　[★]

英: anthelmintic, anthelmintics
ラ: anthelmintica
関

http://en.wikipedia.org/wiki/Anthelmintic

antiplatyhelmintic agents	Antitrematodals (schistosomicides)	binds tubulin	benzimidazole (Triclabendazole#)
		acetylcholinesterase inhibitor	phosphonic acid (metrifonate)
		Other/unknown	quinoline (praziquantel#, oxamniquine#) · phenol (bithionol) · thiazole ([[niridazole]) · arylsulfonate (stibophen)
	anticestodals (taeniacides)	binds tubulin	benzimidazole (albendazole#)
	anticestodals (taeniacides)	Other/unknown	salicylanilide (niclosamide)# · aminoacridine (quinacrine) · butyrophenone (desaspidin) · chlorophenol (dichlorophen)
antinematodal agents (macrofilaricides)		binds tubulin	benzimidazole (mebendazole#, thiabendazole, albendazole#, fenbendazole, ciclobendazole, flubendazole)
		chloride channel	macrolide (ivermectin#)
		NMDA	tetrahydropyrimidine (pyrantel#, pyrantel pamoate, oxantel)
		Other/unknown	piperazine (piperazine · diethylcarbamazine#) · thiazole (levamisole#) · quinolinium (pyrvinium) · benzylammonium (bephenium) · naphthalenesulfonate (suramin#) · tribendimidine

「スラミン」

　　[★]

英: suramin
化: スラミンナトリウム

「suramin sodium」

　　[★]

スラミンナトリウム

関: suramin

[1] Walter Sneader. Drug Discovery: A History. John Wiley & Sons, 2005 ISBN 9780471899792

[2] Fourneau, E.; Th; Vallée, J. (1924). "Sur une nouvelle série de médicaments trypanocides". C. R. Séances Acad. Sci. 178: 675.

[3] "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.

[pmid14728611-4] Darsaud A, Chevrier C, Bourdon L, Dumas M, Buguet A, Bouteille B (January 2004). "Megazol combined with suramin improves a new diagnosis index of the early meningo-encephalitic phase of experimental African trypanosomiasis". Trop. Med. Int. Health 9 (1): 83–91. doi:10.1046/j.1365-3156.2003.01154.x. PMID 14728611.

[pmid678497-5] Anderson J, Fuglsang H (July 1978). "Further studies on the treatment of ocular onchocerciasis with diethylcarbamazine and suramin". Br J Ophthalmol 62 (7): 450–7. doi:10.1136/bjo.62.7.450. PMC 1043255. PMID 678497.

[6] "Lack of response to suramin in patients with AIDS and AIDS-related complex." 82. Mar 1987. pp. 615–20. PMID 3548350.

[pmid15484217-7] Ahles TA, Herndon JE, Small EJ, et al. (November 2004). "Quality of life impact of three different doses of suramin in patients with metastatic hormone-refractory prostate carcinoma: results of Intergroup O159/Cancer and Leukemia Group B 9480". Cancer 101 (10): 2202–8. doi:10.1002/cncr.20655. PMID 15484217.

[8] ttp://medicalxpress.com/news/2013-03-drug-treatment-autism-symptoms-mouse.html

[9] ttp://news.sciencemag.org/biology/2014/06/century-old-drug-reverses-signs-autism-mice

[10] ttp://www.nature.com/tp/journal/v4/n6/full/tp201433a.html

[pmid16968944-11] Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Knight GE, Fumagalli M, Gachet C, Jacobson KA, Weisman GA. (September 2006). "International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy". Pharmacol Rev. 58 (3): 281–341. doi:10.1124/pr.58.3.3. PMC 3471216. PMID 16968944.

[pmid11171941-12] Khakh BS, Burnstock G, Kennedy C, King BF, North RA, Séguéla P, Voigt M, Humphrey PP. (March 2001). "International union of pharmacology. XXIV. Current status of the nomenclature and properties of P2X receptors and their subunits". Pharmacol Rev. 53 (1): 107–118. PMID 11171941.

[pmid16056233-13] Wolner I, Kassack MU, Ullmann H, Karel A, Hohenegger M (October 2005). "Use-dependent inhibition of the skeletal muscle ryanodine receptor by the suramin analogue NF676". Br. J. Pharmacol. 146 (4): 525–33. doi:10.1038/sj.bjp.0706359. PMC 1751178. PMID 16056233.

[pmid18667993-14] Erguven M, Akev N, Ozdemir A, Karabulut E, Bilir A (August 2008). "The inhibitory effect of suramin on telomerase activity and spheroid growth of C6 glioma cells". Med. Sci. Monit. 14 (8): BR165–73. PMID 18667993.

[Mastrangelo2012-15] Mastrangelo E, Pezzullo M, Tarantino D, Petazzi R, Germani F, Kramer D, Robel I, Rohayem J, Bolognesi M, Milani M (2012) Structure-based inhibition of norovirus RNA-dependent RNA-polymerases. J Mol Biol

[pmid8700151-16] Beindl W, Mitterauer T, Hohenegger M, Ijzerman AP, Nanoff C, Freissmuth M. (August 1996). "Inhibition of receptor/G protein coupling by suramin analogues". ol. Pharmacology. 50 (2): 415–23. PMID 8700151.

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suramin