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Chemical Compound Review

AG-J-43958     1-[(4-morpholin-4-yl-1,2,5- thiadiazol-3...

Synonyms: SureCN1587691, CHEBI:39465, CCG-205263, KST-1B2826, AC1L1KFQ, ...
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Disease relevance of timolol


Psychiatry related information on timolol


High impact information on timolol


Chemical compound and disease context of timolol


Biological context of timolol


Anatomical context of timolol


Associations of timolol with other chemical compounds

  • Impressive effects on mortality and morbidity have been obtained with propranolol, timolol, and metoprolol, which are noncardioselective as well as more beta 1-selective (metoprolol), but they are all lacking intrinsic sympathomimetic activity and, furthermore, have a relatively high degree of lipophilicity [27].
  • Blockade of cardiac beta-adrenoceptors was assessed by determining the dose ratios (DR) of isoproterenol infusions required to increase heart rate by 25 beats/min before and after timolol infusion [28].
  • Second, beta-adrenoceptor blockade by timolol but not alpha-adrenoceptor blockade by prazosin prevented the noradrenaline-induced up-regulation of Gi alpha proteins [29].
  • Hence timolol metabolism appears to be subject to debrisoquin-type polymorphism, which results in interphenotypic variation in plasma concentration and beta-blocking effect [30].
  • The level of cardiac vagal inhibition, estimated by the heart rate change after atropine (0.04 mg/kg intravenously), was similar in placebo and on timolol, thereby permitting comparisons of BRS [31].

Gene context of timolol


Analytical, diagnostic and therapeutic context of timolol

  • Five (25%) of 20 patients in the placebo group and 14 (73.7%) of 19 patients with confirmed infarction in the timolol group developed a left ventricular apical thrombus as detected by two-dimensional echocardiography from 2 to 10 days after inclusion (p less than .005) [37].
  • Right heart catheterization was performed in all 20 patients after two weeks of the first placebo and after five weeks of timolol or propranolol [38].
  • Bilateral, but not unilateral, MS infusions of the beta-antagonist timolol (3.75 microg, 8.7 nmol) decreased EEG indices of arousal in the lightly anesthetized preparation [39].
  • Thus, timolol altered myocardial blood flow during exercise by two separate mechanisms: a negative chronotropic effect, and a significant selective reduction of subepicardial perfusion independent of changes in heart rate or blood pressure with transmural redistribution of flow toward the subendocardium [40].
  • Mass of necrosis/mass at risk was significantly smaller in the timolol-treated reperfusion group (27.3 +/- 2.7%) versus saline reperfusion alone (46.5 +/- 5.6%) (p less than 0.005) [24].


  1. Timolol for vasomotor rhinitis. Sheeler, R. N. Engl. J. Med. (1981) [Pubmed]
  2. Timolol in the treatment of open angle glaucoma. Kosman, M.E. JAMA (1979) [Pubmed]
  3. Timolol-induced bronchospasm. Dunn, M. JAMA (1982) [Pubmed]
  4. Migraine prevention with timolol. A double-blind crossover study. Stellar, S., Ahrens, S.P., Meibohm, A.R., Reines, S.A. JAMA (1984) [Pubmed]
  5. Timolol topically and diabetes mellitus. Angelo-Nielsen, K. JAMA (1980) [Pubmed]
  6. Syncope and visual hallucinations, apparently from timolol. Yates, D. JAMA (1980) [Pubmed]
  7. Timolol-related reduction in mortality and reinfarction in patients ages 65-75 years surviving acute myocardial infarction. Prepared for the Norwegian Multicentre Study Group. Gundersen, T., Abrahamsen, A.M., Kjekshus, J., Rønnevik, P.K. Circulation (1982) [Pubmed]
  8. Consolidation of memory for odor-reward association: beta-adrenergic receptor involvement in the late phase. Sara, S.J., Roullet, P., Przybyslawski, J. Learn. Mem. (1999) [Pubmed]
  9. Patient compliance and the "usefulness product" of timolol. Worthen, D.M. Survey of ophthalmology. (1979) [Pubmed]
  10. Latanoprost and timolol combination therapy vs monotherapy: one-year randomized trial. Higginbotham, E.J., Feldman, R., Stiles, M., Dubiner, H. Arch. Ophthalmol. (2002) [Pubmed]
  11. Six-year follow-up of the Norwegian multicenter study on timolol after myocardial infarction. Bellin, E.Y. N. Engl. J. Med. (1986) [Pubmed]
  12. Frequency-dependent noradrenergic modulation of long-term potentiation in the hippocampus. Hopkins, W.F., Johnston, D. Science (1984) [Pubmed]
  13. Pharmacogenetic explanation for excessive beta-blockade following timolol eye drops. Potential for oral-ophthalmic drug interaction. Edeki, T.I., He, H., Wood, A.J. JAMA (1995) [Pubmed]
  14. Effects of timolol and hydrochlorothiazide on blood-pressure and plasma renin activity. Double-blind factorial trial. Chalmers, J., Tiller, D., Horvath, J., Bune, A. Lancet (1976) [Pubmed]
  15. Bradycardia induced by interaction between quinidine and ophthalmic timolol. Dinai, Y., Sharir, M., Naveh, N., Halkin, H. Ann. Intern. Med. (1985) [Pubmed]
  16. Comparative effects of propranolol, timolol and metoprolol on myocardial infarct size after experimental coronary artery occlusion. Vik-Mo, H., Maroko, P.R., Ribeiro, L.G. J. Am. Coll. Cardiol. (1984) [Pubmed]
  17. Duration of action of beta blockers. Johansson, S.R., McCall, M., Wilhelmsson, C., Vedin, J.A. Clin. Pharmacol. Ther. (1980) [Pubmed]
  18. The portal pressure response to beta-blockade is greater in cirrhotic patients without varices than in those with varices. Escorsell, A., Ferayorni, L., Bosch, J., García-Pagán, J.C., García-Tsao, G., Grace, N.D., Rodés, J., Groszmann, R.J. Gastroenterology (1997) [Pubmed]
  19. Avoiding unsuspected respiratory side-effects of topical timolol with cardioselective or sympathomimetic agents. Diggory, P., Cassels-Brown, A., Vail, A., Abbey, L.M., Hillman, J.S. Lancet (1995) [Pubmed]
  20. Cardiovascular effects of ophthalmic timolol. Leier, C.V., Baker, N.D., Weber, P.A. Ann. Intern. Med. (1986) [Pubmed]
  21. Hemodynamic, reflexive, and metabolic alterations induced by acute and chronic timolol therapy in hypertensive man. Dunn, F.G., de Carvalho, J.G., Frohlich, E.D. Circulation (1978) [Pubmed]
  22. Timolol, carotid sinus hypersensitivity, and elderly patients. Mulcahy, R., Allcock, L., O'Shea, D. Lancet (1998) [Pubmed]
  23. Efficacy and safety of timolol for prevention of supraventricular tachyarrhythmias after coronary artery bypass surgery. White, H.D., Antman, E.M., Glynn, M.A., Collins, J.J., Cohn, L.H., Shemin, R.J., Friedman, P.L. Circulation (1984) [Pubmed]
  24. Enhancement of salvage of reperfused myocardium by early beta-adrenergic blockade (timolol). Hammerman, H., Kloner, R.A., Briggs, L.L., Braunwald, E. J. Am. Coll. Cardiol. (1984) [Pubmed]
  25. Pulmonary effects of topical timolol. Charan, N.B., Lakshminarayan, S. Arch. Intern. Med. (1980) [Pubmed]
  26. Comparisons of the interaction of propranolol and timolol with model and biological membrane systems. Herbette, L., Katz, A.M., Sturtevant, J.M. Mol. Pharmacol. (1983) [Pubmed]
  27. Myocardial infarction. Effects of beta-blockade. Hjalmarson, A., Olsson, G. Circulation (1991) [Pubmed]
  28. Beta-blocking effects of timolol at low plasma concentrations. Kaila, T., Huupponen, R., Karhuvaara, S., Havula, P., Scheinin, M., Iisalo, E., Salminen, L. Clin. Pharmacol. Ther. (1991) [Pubmed]
  29. Pseudomonas exotoxin A prevents beta-adrenoceptor-induced upregulation of Gi protein alpha-subunits and adenylyl cyclase desensitization in rat heart muscle cells. Reithmann, C., Gierschik, P., Müller, U., Werdan, K., Jakobs, K.H. Mol. Pharmacol. (1990) [Pubmed]
  30. Pharmacokinetics and beta-blocking effects of timolol in poor and extensive metabolizers of debrisoquin. McGourty, J.C., Silas, J.H., Fleming, J.J., McBurney, A., Ward, J.W. Clin. Pharmacol. Ther. (1985) [Pubmed]
  31. Effect of beta adrenoceptor antagonists on baroreceptor reflex sensitivity in hypertension. Simon, G., Kiowski, W., Julius, S. Clin. Pharmacol. Ther. (1977) [Pubmed]
  32. Beta-adrenoceptor-mediated inhibition of IFN-gamma, IL-3, and GM-CSF mRNA accumulation in activated human T lymphocytes is solely mediated by the beta2-adrenoceptor subtype. Borger, P., Hoekstra, Y., Esselink, M.T., Postma, D.S., Zaagsma, J., Vellenga, E., Kauffman, H.F. Am. J. Respir. Cell Mol. Biol. (1998) [Pubmed]
  33. Conjunctival proinflammatory and proapoptotic effects of latanoprost and preserved and unpreserved timolol: an ex vivo and in vitro study. Pisella, P.J., Debbasch, C., Hamard, P., Creuzot-Garcher, C., Rat, P., Brignole, F., Baudouin, C. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
  34. Polymorphisms of genes CYP2D6, ADRB1 and GNAS1 in pharmacokinetics and systemic effects of ophthalmic timolol. A pilot study. Nieminen, T., Uusitalo, H., Mäenpää, J., Turjanmaa, V., Rane, A., Lundgren, S., Ropo, A., Rontu, R., Lehtimäki, T., Kähönen, M. Eur. J. Clin. Pharmacol. (2005) [Pubmed]
  35. Study of effects of antiglaucoma eye drops on N-methyl-D-aspartate-induced retinal damage. Metoki, T., Ohguro, H., Ohguro, I., Mamiya, K., Ito, T., Nakazawa, M. Jpn. J. Ophthalmol. (2005) [Pubmed]
  36. Polymorphism of the beta-2 adrenoceptor and IOP lowering potency of topical timolol in healthy subjects. Fuchsjager-Mayrl, G., Markovic, O., Losert, D., Lucas, T., Wachek, V., Muller, M., Schmetterer, L. Mol. Vis. (2005) [Pubmed]
  37. Increased occurrence of left ventricular thrombi during early treatment with timolol in patients with acute myocardial infarction. Johannessen, K.A., Nordrehaug, J.E., von der Lippe, G. Circulation (1987) [Pubmed]
  38. Effect of timolol versus propranolol on hypertension and hemodynamics. Aronow, W.S., Ferlinz, J., Del Vicario, M., Moorthy, K., King, J., Cassidy, J. Circulation (1976) [Pubmed]
  39. Modulation of forebrain electroencephalographic activity in halothane-anesthetized rat via actions of noradrenergic beta-receptors within the medial septal region. Berridge, C.W., Bolen, S.J., Manley, M.S., Foote, S.L. J. Neurosci. (1996) [Pubmed]
  40. Effect of beta-adrenergic blockade with timolol on myocardial blood flow during exercise after myocardial infarction in the dog. Herzog, C.A., Aeppli, D.P., Bache, R.J. J. Am. Coll. Cardiol. (1984) [Pubmed]
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