|Systematic (IUPAC) name|
|Biological half-life||2.5-5 hours|
|ATC code||C07 S01|
|Molecular mass||316.421 g/mol|
|(what is this?)|
It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.
In its oral form, it is used:
In its ophthalmic form 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.
The 20 January 2014, issue of the Medical Journal of Australia (MJA) reported on topical timolol being successfully used to treat chronic leg ulcers in 92-year-old patient. <1>
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.
- 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
- IOTIM-B - timolol and brimonidine
- Cosopt - timolol maleate and dorzolamide hydrochloride
- DuoTrav - timolol and travoprost
- Xalacom (Pfizer) - timolol and latanoprost
- Brimoeye T ( Preservative free) Brimonidine+Timolol -( Eyekare Kilitch)
- Travaprositn T ( Preservative Free) Travaprost+Timolol- (Eyekare Kilitch)
- 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.
- In Jordan: Apimol
- In Israel: V-Optic drops.
- In India: Timoeye, IOTIM.
Preparation of the 1,2,5-thiadiazole intermediate (4) involves the reaction of the carbamoyl cyanide (1) with sulfur monochloride. The reaction can be rationalized by invoking the addition of the reagent across the nitrile group to form an intermediate such as 2. Displacement of the chlorine on the sulfur by the amide nitrogen serves to close the ring; tautomerization to the all-enol form gives the observed product (3). The free hydroxyl is then tosylated (4).
The required side chain glycol R-glyceraldehyde (5) is available commercially as a degradation product from mannitol. Thus, reductive amination of the aldehyde with tert-butylamine gives the ethanolamine side chain (6) in chiral form.
- "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- 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.
- Strohmaier, K; Snyder, E; Adamsons, I (Jul 1998). "A multicenter study comparing dorzolamide and pilocarpine as adjunctive therapy to timolol: patient preference and impact on daily life". J Am Optom Assoc 69 (7): 441–51. PMID 9697378.
- Sena DF, Lindsley K (2013). "Neuroprotection for treatment of glaucoma in adults". Cochrane Database Syst Rev 2 (2): CD006539. doi:10.1002/14651858.CD006539.pub3. PMC 3478138. PMID 20166085.
- Weinstock, Leonard M. (1976). "Synthesis of the .beta.-adrenergic blocking agent timolol from optically active precursors". The Journal of Organic Chemistry 41 (19): 3121–3124. doi:10.1021/jo00881a011. PMID 9497.
- Wasson, B. K.; Gibson, W. K.; Stuart, R. S.; Williams, H. W. R.; Yates, C. H. (1972). ".beta.-Adrenergic blocking agents. 3-(3-Substituted-amino-2-hydroxypropoxy)-4-substituted-1,2,5-thiadiazoles". Journal of Medicinal Chemistry 15 (6): 651. doi:10.1021/jm00276a022. PMID 4402289.
- Weinstock, Leonard M.; Mulvey, Dennis M.; Tull, Roger. (1976). "Synthesis of the .beta.-adrenergic blocking agent timolol from optically active precursors". The Journal of Organic Chemistry 41 (19): 3121–3124. doi:10.1021/jo00881a011. PMID 9497.