Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/06/22 20:05:33」(JST)

wiki en

Tolmetin /ˈtɒlmətɨn/ is a non-steroidal anti-inflammatory drug of the arylalkanoic acids. It is used primarily to reduce hormones that cause pain, swelling, tenderness, and stiffness in conditions such as osteoarthritis and rheumatoid arthritis, including juvenile rheumatoid arthritis. In the United States it is marketed as Tolectin and comes as a tablet or capsule.

Clinical trials

Tolmetin is applicable in the treatment of rheumatoid arthritis,^[1]^[2] osteoarthrosis,^[3]^[4] pain,^[5] and ankylosing spondylitis.^[6]

Mechanism of action

Although the mechanism of action of tolmetin is unknown, research involving humans and animals has shown that tolmetin does not achieve anti-inflammatory response by stimulation of the adrenal or pituitary gland, but it has shown tolmetin restrains prostaglandin synthetase in vitro and reduces plasma levels of prostaglandin E, possibly causing the anti-inflammatory response.

When tested in rats tolmetin prevented experimentally stimulated polyarthritis and reduced inflammation. In patients with rheumatoid arthritis or osteoarthritis tolmetin restrained disease activity as efficiently as aspirin and indometacin, although the occurrence of mild gastrointestinal adverse effects and tinnitus was lower in patients treated with tolmetin than it was with aspirin-treated patients and the occurrence of adverse effects of the central nervous system was lower with tolmetin than it was with indometacin.^[7]

Side effects

Tolmetin can increase the risk of heart or circulatory conditions such as heart attacks and strokes. It should not be taken shortly before or after coronary artery bypass surgery.^[8] Tolmetin can also increase the risk of gastrointestinal conditions such as perforation or bleeding, which is fatal. Antacids can be taken with tolmetin to relieve stomachaches that often occur.^[8] Overdose can result in drowsiness, nausea, epigastric pain, and vomiting.

Chemical synthesis

Tolmetin can be synthesized by the following route:^[9]

J. Carson, U.S. Pat. 3.752.826 (1973).
J.R. Carson, Fr. Pat. 1.574.570 (1969)

References

^ Cordrey L J (1976). "Tolmetin sodium, a new anti-arthritis drug: double-blind and long-term studies". Journal of the American Geriatrics Society 24 (10): 440–446. PMID 61224.
^ Cardoe N; Steele C E (1976–1977). "A double-blind crossover comparison of tolmetin sodium and phenylbutazone in the treatment of rheumatoid arthritis". Current medical research and opinion 4 (10): 688–694. doi:10.1185/03007997609112003. PMID 800970.
^ Liyanage S P; Steele C E (1977–1978). "Tolmetin in osteoarthrosis of the hip and knee: double-blind crossover trials". Current medical research and opinion 5 (4): 299–305. doi:10.1185/03007997709110184. PMID 343992.
^ Davies, J; Dixon, AS; Steele, CE (1980). "Tolmetin sodium and indomethacin in the treatment of osteoarthrosis of the hip: a double-blind crossover study". Current medical research and opinion 7 (2): 115–20. doi:10.1185/03007998009112037. PMID 7002480.
^ Stacher, G; Bauer, P; Ehn, I; Schreiber, E (1979). "Effects of tolmetin, paracetamol, and of two combinations of tolmetin and paracetamol as compared to placebo on experimentally induced pain. A double blind study". International journal of clinical pharmacology and biopharmacy 17 (6): 250–5. PMID 381221.
^ Calin, A (1983). "Clinical use of tolmetin sodium in patients with ankylosing spondylitis: a review". Journal of clinical pharmacology 23 (7): 301–8. doi:10.1002/j.1552-4604.1983.tb02740.x. PMID 6350376.
^ "Tolmetin". DrugBank. Retrieved 2007-07-02.
^ ^a ^b "Tolmetin". MedlinePlus. Archived from the original on 2007-06-10. Retrieved 2007-07-02.
^ Carson, John R.; McKinstry, Doris N.; Wong, Stewart (1971). "5-Benzoyl-1-methylpyrrole-2-acetic acids as antiinflammatory agents". Journal of Medicinal Chemistry 14 (7): 646. doi:10.1021/jm00289a026.

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. 非選択性非ステロイド性抗炎症剤（NSAIDs）：心血管系への有害作用 nonselective nsaids adverse cardiovascular effects
2. 小児の脊椎関節炎 spondyloarthritis in children
3. 非ステロイド性抗炎症剤（NSAIDs）（アスピリンを含む）：胃十二指腸障害の一次予防 nsaids including aspirin primary prevention of gastroduodenal toxicity
4. 少関節型若年性特発性関節炎 oligoarticular juvenile idiopathic arthritis
5. 妊娠中および授乳中のリウマチ性疾患における抗炎症剤および免疫抑制剤の使用 use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation

English Journal

Synthesis of Tolmetin Hydrazide-Hydrazones and Discovery of a Potent Apoptosis Inducer in Colon Cancer Cells.

Küçükgüzel ŞG1, Koç D1, Çıkla-Süzgün P1, Özsavcı D2, Bingöl-Özakpınar Ö2, Mega-Tiber P3, Orun O3, Erzincan P4, Sağ-Erdem S4, Şahin F5.
Archiv der Pharmazie.Arch Pharm (Weinheim).2015 Oct;348(10):730-42. doi: 10.1002/ardp.201500178. Epub 2015 Aug 19.
Tolmetin hydrazide and a novel series of tolmetin hydrazide-hydrazones 4a-l were synthesized in this study. The structures of the new compounds were determined by spectral (FT-IR, (1)H NMR) methods. N'-[(2,6-Dichlorophenyl)methylidene]-2-[1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl]acetohydrazide (4
PMID 26287512

Significantly Different Covalent Binding of Oxidative Metabolites, Acyl Glucuronides, and S-Acyl CoA Conjugates Formed from Xenobiotic Carboxylic Acids in Human Liver Microsomes.

Darnell M, Breitholtz K, Isin EM, Jurva U, Weidolf L.
Chemical research in toxicology.Chem Res Toxicol.2015 May 18;28(5):886-96. doi: 10.1021/tx500514z. Epub 2015 Apr 8.
Xenobiotic carboxylic acids may be metabolized to oxidative metabolites, acyl glucuronides, and/or S-acyl-CoA thioesters (CoA conjugates) in vitro, e.g., in hepatocytes, and in vivo. These metabolites can potentially be reactive species and bind covalently to tissue proteins and are generally consid
PMID 25803559

The influence of API concentration on the roller compaction process: modeling and prediction of the post compacted ribbon, granule and tablet properties using multivariate data analysis.

Boersen N1, Carvajal MT, Morris KR, Peck GE, Pinal R.
Drug development and industrial pharmacy.Drug Dev Ind Pharm.2015;41(9):1470-8. doi: 10.3109/03639045.2014.958754. Epub 2015 Jul 21.
OBJECTIVE: While previous research has demonstrated roller compaction operating parameters strongly influence the properties of the final product, a greater emphasis might be placed on the raw material attributes of the formulation. There were two main objectives to this study. First, to assess the
PMID 25212638

Japanese Journal

アシルグルクロニドによる細胞毒性のメカニズム解析

宮下泰志,深見達基,中島美紀,横井毅
日本毒性学会学術年会 40.1(0), 2003157, 2013
… 本研究ではAGを生成する薬物としてdiclofenac (DCF)，ibuprofen (Ibu)，naproxen (Nap)，probenecid (Pro) およびtolmetin (Tol) を用いて，AGにより生じる細胞毒性を，炎症性因子を指標として評価し，その機序を解明することを目的とした。 …
NAID 130004676750

非ステロイド性抗炎症薬（non-steroidal anti-inflammatory drugs）の戦略的用法を目指して：ペルオキシダーゼとの反応性を基にした非ステロイド性抗炎症薬の分類

三浦俊明
YAKUGAKU ZASSHI 133(6), 681-689, 2013
… Class 3 includes aspirin, nimesulide, tolmetin, and arylpropionic acid derivatives, including ibuprofen and the coxibs such as celecoxib and rofecoxib, which are not substrates for HRP or PGHS peroxidase. …
NAID 130003361963

A Simple Method to Evaluate Reactivity of Acylglucuronides Optimized for Early Stage Drug Discovery

Jinno Norimasa,Ohashi Shigeki,Tagashira Mizuka [他],Kohira Terutomo,Yamada Shizuo
Biological and Pharmaceutical Bulletin 36(9), 1509-1513, 2013
… We evaluated the half-lives of 10 drugs: 3 safe drugs (telmisartan, gemfibrozil and flufenamic acid) and 7 withdrawn or warning drugs (zomepirac, diclofenac, furosemide, ibuprofen, S-naproxen, probenecid and tolmetin). …
NAID 130003361534

「トルメチン」

Tolmetin
Systematic (IUPAC) name
	[1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl]acetic acid
Clinical data
Trade names	Tolectin
AHFS/Drugs.com	monograph
MedlinePlus	a681033
Legal status	Prescription Only (S4) (AU)
Routes	oral
Pharmacokinetic data
Half-life	1-2 hours, next phase up to 5 hours
Identifiers
CAS number	26171-23-3
ATC code	M01AB03 M02AA21
PubChem	CID 5509
DrugBank	DB00500
ChemSpider	5308
UNII	D8K2JPN18B
KEGG	D02355
ChEBI	CHEBI:71941
ChEMBL	CHEMBL1020
Chemical data
Formula	C15H15NO3
Mol. mass	257.285 g/mol
	SMILES O=C(c1ccc(n1C)CC(=O)O)c2ccc(cc2)C;
	InChI InChI=1S/C15H15NO3/c1-10-3-5-11(6-4-10)15(19)13-8-7-12(16(13)2)9-14(17)18/h3-8H,9H2,1-2H3,(H,17,18) ; Key:UPSPUYADGBWSHF-UHFFFAOYSA-N ;
(what is this?) (verify)

　　[★]

英: tolmetin
化: トルメチンナトリウム tolmetin sodium
商: トレクチン

酸性非ステロイド性抗炎症薬

「tolmetin sodium」

　　[★] トルメチン。トルメチンナトリウム

[1] Cordrey L J (1976). "Tolmetin sodium, a new anti-arthritis drug: double-blind and long-term studies". Journal of the American Geriatrics Society 24 (10): 440–446. PMID 61224.

[2] Cardoe N; Steele C E (1976–1977). "A double-blind crossover comparison of tolmetin sodium and phenylbutazone in the treatment of rheumatoid arthritis". Current medical research and opinion 4 (10): 688–694. doi:10.1185/03007997609112003. PMID 800970.

[3] Liyanage S P; Steele C E (1977–1978). "Tolmetin in osteoarthrosis of the hip and knee: double-blind crossover trials". Current medical research and opinion 5 (4): 299–305. doi:10.1185/03007997709110184. PMID 343992.

[4] Davies, J; Dixon, AS; Steele, CE (1980). "Tolmetin sodium and indomethacin in the treatment of osteoarthrosis of the hip: a double-blind crossover study". Current medical research and opinion 7 (2): 115–20. doi:10.1185/03007998009112037. PMID 7002480.

[5] Stacher, G; Bauer, P; Ehn, I; Schreiber, E (1979). "Effects of tolmetin, paracetamol, and of two combinations of tolmetin and paracetamol as compared to placebo on experimentally induced pain. A double blind study". International journal of clinical pharmacology and biopharmacy 17 (6): 250–5. PMID 381221.

[6] Calin, A (1983). "Clinical use of tolmetin sodium in patients with ankylosing spondylitis: a review". Journal of clinical pharmacology 23 (7): 301–8. doi:10.1002/j.1552-4604.1983.tb02740.x. PMID 6350376.

[DrugBank-7] "Tolmetin". DrugBank. Retrieved 2007-07-02.

[MedlinePlus-8] "Tolmetin". MedlinePlus. Archived from the original on 2007-06-10. Retrieved 2007-07-02.

[9] Carson, John R.; McKinstry, Doris N.; Wong, Stewart (1971). "5-Benzoyl-1-methylpyrrole-2-acetic acids as antiinflammatory agents". Journal of Medicinal Chemistry 14 (7): 646. doi:10.1021/jm00289a026.

匿名

検索

案内

案内

tolmetin