Timolol

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Structural formula
Timolol structural formula
General
Non-proprietary name Timolol
other names

(-) - ( S ) -1- ( tert -Butylamino) -3- (4-morpholino-1,2,5-thiadiazol-3-yloxy) propan-2-ol

Molecular formula C 13 H 24 N 4 O 3 S
Brief description

crystalline solid

External identifiers / databases
CAS number
  • 26839-75-8
  • 26921-17-5 (monosalt of maleic acid)
EC number 248-032-6
ECHA InfoCard 100,043,651
PubChem 33624
ChemSpider 31013
DrugBank DB00373
Wikidata Q413994
Drug information
ATC code
Drug class

Beta blockers

Mechanism of action

nonselective β-adrenoceptor - Antagonist

properties
Molar mass 316.42 g · mol -1
Physical state

firmly

Melting point

71.5-72.5 ° C

pK s value

9.4

solubility

slightly soluble in water (2740 mg l −1 at 25 ° C)

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances

Maleate

07 - Warning 08 - Dangerous to health

Caution

H and P phrases H: 302-361
P: 281
Toxicological data

900 mg kg −1 ( LD 50 ,  rat ,  oral )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Timolol is a chiral , enantiomerically pure drug from the group of beta blockers and is mainly used in eye drops for the treatment of open-angle glaucoma (glaucoma).

pharmacology

Timolol belongs to the group of non-selective beta blockers because it does not specifically bind to the β 1 -adrenoceptors . It has no intrinsic sympathomimetic activity ( ISA ). Timolol inhibits the β 2 -adrenoceptors in the ciliary body of the eye and therefore lowers the production of aqueous humor. Due to the reduced formation of aqueous humor, the intraocular pressure is reduced. The relative potency of timolol compared to propranolol is 6.

Pharmacokinetics

The fat-soluble timolol is well absorbed after oral ingestion, the bioavailability of timolol is around 50 to 60%. The plasma half-life of timolol is approximately 4 to 5 hours. It is metabolized up to 80% in the liver . The plasma protein binding of timolol is 60%. 30% of timolol is excreted in the kidneys.

synthesis

There are several synthetic routes for timolol. Starting from 3,4-dichloro-1,2,5-thiadiazole and morpholine, first racemic timolol is produced in a five-step process. The resolution with (+) - tartaric acid then yields ( S ) -timolol, which is used as a medicinal substance. Alternatively, enantiomerically pure timolol can also be prepared from D- glyceraldehyde - avoiding racemate resolution.

Trade names

Monopreparations

Arutimol (D), Betimol (A), Chibro-Timoptol (D), Dispatim (D), NyoGel (D), Nyolol (CH), numerous generics (D)

Combination preparations

AZARGA (A), Combigan (D, CH), Cosopt (D, CH), DuoTrav (D, CH), Fotil (D), Ganfort (D, CH), TP-Ophtal (D), Xalacom (D, CH )

literature

  • T. Karow / R. Lang-Roth: General and special pharmacology and toxicology . (2003) pp. 62-66
  • G. Herold: Internal Medicine (2004)

Individual evidence

  1. ↑ a b entry on timolol. In: Römpp Online . Georg Thieme Verlag, accessed on December 28, 2014.
  2. ^ V. Martinez, MI Maguregui, RM Jimenez, RM Alonso: Determination of the pKa values ​​of β-blockers by automated potentiometric titrations. In: Journal of Pharmaceutical and Biomedical Analysis . 23, 2000, pp. 459-468, doi: 10.1016 / S0731-7085 (00) 00324-1 .
  3. ↑ Entry on timolol in the ChemIDplus database of the United States National Library of Medicine (NLM) .
  4. ↑ a b data sheet Timolol maleate salt from Sigma-Aldrich , accessed on April 24, 2011 ( PDF ).
  5. ↑ Entry on timolol in the DrugBank of the University of Alberta .
  6. ↑ Axel Kleemann , Jürgen Engel, Bernd Kutscher and Dieter Reichert: Pharmaceutical Substances , 4th edition (2000) 2 volumes published by Thieme-Verlag Stuttgart, pp. 2043-2045, ISBN 978-1-58890-031-9 ; online since 2003 with biannual additions and updates.