WordNet

a salt or ester of maleic acid; used as a nontricyclic antidepressant drug for psychomotor activation
a beta blocker (trade name Blocadren) administered after heart attacks (同)Blocadren

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/05/09 19:21:32」(JST)

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Timolol maleate is a non-selective beta-adrenergic receptor antagonist indicated for treating glaucoma, heart attacks and hypertension.

Uses [edit]

In its oral form (Blocadren), it is used:

to treat high blood pressure
to prevent heart attacks
to prevent migraine headaches^[1]

In its ophthalmic form (brand names Timoptol in Italy; Timoptic), it is used to treat open-angle and occasionally secondary glaucoma by reducing aqueous humour production through blockage of the beta receptors on the ciliary epithelium. The pharmacological mechanism by which it actually does this is still unknown. First beta-blocker approved for topical use in treatment of glaucoma in the USA (1978). With monotherapy, depresses IOP 18-34% below baseline within first few treatments. However, there are short-term escape and long-term drift effects in some patients. That is, tolerance develops. May reduce extent of diurnal IOP curve up to 50%. IOP higher during sleep. 5-10x more potent beta-blocker than propranolol. Light sensitive; preserved with 0.01% benzalkonium Cl (and also comes BAC free). Can also be used in adjunctive therapy with pilocarpine or CAIs.

Side effects [edit]

The most serious possible side effects include cardiac arrhythmias and severe bronchospasms. Timolol can also lead to fainting, congestive heart failure, depression, confusion, worsening of Raynaud's syndrome and impotence.

Usual dosage [edit]

Children and Adults: Ophthalmic: Initial: 0.25% solution, instill 1 drop twice daily; increase to 0.5% solution if response not adequate; decrease to 1 drop/day if *controlled; do not exceed 2 drops twice daily of 0.5% solution Adults: Oral:
Hypertension: Initial: 10 mg twice daily, increase gradually every 14 days, usual dosage: 20–40 mg/day in 2 divided doses; maximum: 60 mg/day
Prevention of myocardial infarction: 10 mg twice daily initiated within 1–6 weeks after infarction
Migraine headache: Initial: 10 mg twice daily, increase to maximum of 30 mg/day

Formulations [edit]

Gel-forming solution, ophthalmic, as maleate (Timoptic-XE): 0.25% (2.5 mL, 5 mL); 0.5% (2.5 mL, 5 mL)
Solution, ophthalmic, as hemihydrate (Betimol): 0.25% (5 mL, 10 mL, 15 mL); 0.5% (5 mL, 10 mL, 15 mL) [contains benzalkonium chloride]
Solution, ophthalmic, as maleate: 0.25% (5 mL, 10 mL, 15 mL); 0.5% (5 mL, 10 mL, 15 mL) [contains benzalkonium chloride]
Timoptic: 0.25% (5 mL, 10 mL); 0.5% (5 mL, 10 mL) [contains benzalkonium chloride]
Solution, ophthalmic, as maleate [preservative free] (Timoptic OcuDose): 0.25% (0.2 mL);0.5% (0.2 mL) [single use]
Tablet, as maleate (Blocadren): 5 mg, 10 mg, 20 mg

For ophthalmic use, timolol is also available combined with other medications:

Combigan - timolol and brimonidine
Cosopt - timolol maleate and dorzolamide hydrochloride
DuoTrav - timolol and travoprost
Xalacom (Pfizer) - timolol and latanoprost

Brand names [edit]

In Canada: Apo-Timol, Apo-Timop, Gen-Timolol, Nu-Timolol, Phoxal-timolol, PMS-Timolol, Tim-AK, Timoptic, Timoptic-XE.
In the United States: Betimol, Blocadren, Istalol, Timoptic, Timoptic-XE, Timoptic OcuDose.

Chemical synthesis [edit]

References [edit]

^ Dawn A. Marcus; Philip A. Bain (27 February 2009). Effective Migraine Treatment in Pregnant and Lactating Women: A Practical Guide. シュプリンガー・ジャパン株式会社. pp. 141–. ISBN 978-1-60327-438-8. Retrieved 14 November 2010.

External links [edit]

http://dx.doi.org/10.1021/jo00881a011

This drug article relating to the cardiovascular system is a stub. You can help Wikipedia by expanding it.

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1. 幼児血管腫のマネージメント management of infantile hemangiomas
2. 開放隅角緑内障：治療 open angle glaucoma treatment
3. 閉塞隅角緑内障 angle closure glaucoma
4. 中毒性結膜炎 toxic conjunctivitis
5. 成人における片頭痛の予防的治療 preventive treatment of migraine in adults

English Journal

Noradrenergic modulation of glutamate-induced excitatory responses in single neurons of the red nucleus: An electrophysiological study.

Bronzi D1, Licata F1, Li Volsi G2.
Neuroscience.Neuroscience.2015 Aug 6;300:360-9. doi: 10.1016/j.neuroscience.2015.05.038. Epub 2015 May 23.
The effect induced by noradrenaline (NA) on the spiking activity evoked by glutamate (Glu) on single neurons of the mesencephalic red nucleus (RN) of the rat was studied extracellularly. Long-lasting microiontophoretic applications of the amine induced a significant and reversible depression of the
PMID 26012489

Beta-blockers for childhood vascular tumors.

Bayart CB1, Brandling-Bennett HA.
Current opinion in pediatrics.Curr Opin Pediatr.2015 Aug;26(4):454-9. doi: 10.1097/MOP.0000000000000238.
PURPOSE OF REVIEW: Since 2008, beta-blockers have become first-line treatment for infantile hemangiomas, the most common tumor of infancy. Their role is also being explored in the treatment of other childhood vascular tumors.RECENT FINDINGS: Recent research has demonstrated that propranolol is a mor
PMID 26087423

Dual drug delivery from vitamin E loaded contact lenses for glaucoma therapy.

Hsu KH1, Carbia BE2, Plummer C3, Chauhan A4.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V.Eur J Pharm Biopharm.2015 Aug;94:312-21. doi: 10.1016/j.ejpb.2015.06.001. Epub 2015 Jun 10.
Glaucoma patients frequently instill eye drops multiple times each day, which is a cause for reduced compliance. Additionally, eye drops suffer from other limitations including low bioavailability, which can lead to side effects. We propose to develop drug-eluting contact lenses for managing glaucom
PMID 26071799

Japanese Journal

Dynamic Contour Tonometerを用いたトラボプロスト・チモロールマレイン酸塩配合点眼液とビマトプロスト点眼液の眼圧下降率の比較

西村宗作,伊藤初夏,中西正典 [他]
あたらしい眼科 31(10), 1535-1539, 2014-10
NAID 40020248423

乳児血管腫にβブロッカー点眼が奏功した1例

中内一揚,三村治
眼科 56(8), 1009-1015, 2014-07
NAID 40020155100

臨床報告ラタノプロスト・チモロールマレイン酸塩(ザラカム配合点眼液)の使用実態下における安全性と有効性 : 特定使用成績調査中間解析結果報告

吉田愛,森政美香,板東説也 [他]
臨床眼科 68(4), 573-580, 2014-04
NAID 40020044916

「チモロール」

Timolol
Systematic (IUPAC) name
	(S)-1-(tert-butylamino)-3-[(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl)oxy]propan-2-ol
Clinical data
Trade names	Timoptic
AHFS/Drugs.com	monograph
MedlinePlus	a602022
Pregnancy cat.	C (AU) C (US)
Legal status	℞ Prescription only
Routes	oral, Ophthalmic
Pharmacokinetic data
Bioavailability	60%
Metabolism	Hepatic: 80%
Half-life	2.5-5 hours
Excretion	Renal
Identifiers
CAS number	26839-75-8
ATC code	C07AA06
PubChem	CID 33624
IUPHAR ligand	565
DrugBank	DB00373
ChemSpider	31013
UNII	5JKY92S7BR
KEGG	D08600
ChEBI	CHEBI:9599
ChEMBL	CHEMBL499
Chemical data
Formula	C13H24N4O3S
Mol. mass	316.421 g/mol
	SMILES O[C@H](COc1nsnc1N2CCOCC2)CNC(C)(C)C;
	InChI InChI=1S/C13H24N4O3S/c1-13(2,3)14-8-10(18)9-20-12-11(15-21-16-12)17-4-6-19-7-5-17/h10,14,18H,4-9H2,1-3H3/t10-/m0/s1 ; Key:BLJRIMJGRPQVNF-JTQLQIEISA-N ;
(what is this?) (verify);

　　[★]

英: timolol
化: マレイン酸チモロール timolol maleate
商: ブロカドレン BLOCARDEN、チマバック、Timoptic、Betimol; コソプト、ザラカム、チアブート、チモプトール、チモレート、デュオトラバ、ファルチモ、リズモン
関: 眼科用剤

β受容体遮断薬(競合阻害)

薬効薬理

チマバック点眼液0.5％

眼圧下降作用：チマバック点眼液0.5％は，家兎の正常眼圧を用いた試験系において，眼圧下降効果が認められた1）．また，家兎の実験的高眼圧モデルに対しても，眼圧上昇抑制及び下降効果が認められた1）．

チモプトールＸＥ点眼液０．２５％／チモプトールＸＥ点眼液０．５％

1. 眼圧下降作用

ウサギにおけるα-キモトリプシン惹起高眼圧及び水負荷による眼圧上昇試験において、チモロールマレイン酸塩の点眼は有意に眼圧上昇を抑制することが認められている。9)

2. β-受容体遮断作用

ラット、イヌ、ネコにチモロールマレイン酸塩を全身投与した場合、イソプレナリンにより惹起された心拍数、心筋収縮力及び心拍出量の増加は著明に抑制され、本剤のβ-受容体遮断作用はピンドロールと同程度、プロプラノロールより数倍強力である。10)、11) また、チモロールマレイン酸塩は有意の内因性交感神経刺激作用、直接心筋抑制作用、局所麻酔作用を示さない。10)、11)

作用機序

チモプトールＸＥ点眼液０．２５％／チモプトールＸＥ点眼液０．５％

眼圧下降作用機序の詳細は明らかでないが、サル12)、健康成人13) でのフルオロフォトメトリー試験及び緑内障患者でのトノグラフィー試験6)、14) において、チモロールマレイン酸塩の眼圧下降作用は主に房水産生の抑制によることが示唆されている。しかし房水流出率の増加が関与するとの報告もある。15)、16)

添付文書

チマバック点眼液0.5％

http://www.info.pmda.go.jp/go/pack/1319702Q2090_1_06/1319702Q2090_1_06?view=body

チモプトールＸＥ点眼液０．２５％／チモプトールＸＥ点眼液０．５％

http://www.info.pmda.go.jp/go/pack/1319702Q3037_4_01/1319702Q3037_4_01?view=body

「maleate」

　　[★]

マレイン酸、マレイン酸塩、マレイン酸エステル

関: maleic acid

maleic acid

[MarcusBain2009-1] Dawn A. Marcus; Philip A. Bain (27 February 2009). Effective Migraine Treatment in Pregnant and Lactating Women: A Practical Guide. シュプリンガー・ジャパン株式会社. pp. 141–. ISBN 978-1-60327-438-8. Retrieved 14 November 2010.

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案内

案内

timolol maleate