Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new timoptic research articles will be listed here shortly after becoming available to us.
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Medical research on timoptic
J Glaucoma. 2008 June/July; 17(4): 329-331
Madadi P, Koren G, Freeman DJ, Oertel R, Campbell RJ, Trope GE
A 32-year-old lactating woman with open-angle glaucoma used timolol maleate 0.5% eye drops twice daily to her right eye for 6 months. Four milk samples were collected over a span of 6 days. Timolol maleate milk levels were examined by liquid chromatography tandem mass spectrometry and found to be at a mean of 0.12 ng/mL (range, 0 to 0.37 ng/mL). At this level, the theoretical maximum relative infant dose expressed as a percentage of the weight-adjusted maternal dose was 0.012%. As most glaucoma patients administer drops to both eyes, the dosage was duplicated to reflect the more pertinent calculated theoretical relative infant dose of 0.024%. This dose of timolol is unlikely to cause systemic side effects to the healthy breastfed infant.
Structure. 2008 Jun; 16(6): 897-905
Hanson MA, Cherezov V, Griffith MT, Roth CB, Jaakola VP, Chien EY, Velasquez J, Kuhn P, Stevens RC
The role of cholesterol in eukaryotic membrane protein function has been attributed primarily to an influence on membrane fluidity and curvature. We present the 2.8 A resolution crystal structure of a thermally stabilized human beta(2)-adrenergic receptor bound to cholesterol and the partial inverse agonist timolol. The receptors pack as monomers in an antiparallel association with two distinct cholesterol molecules bound per receptor, but not in the packing interface, thereby indicating a structurally relevant cholesterol-binding site between helices I, II, III, and IV. Thermal stability analysis using isothermal denaturation confirms that a cholesterol analog significantly enhances the stability of the receptor. A consensus motif is defined that predicts cholesterol binding for 44% of human class A receptors, suggesting that specific sterol binding is important to the structure and stability of other G protein-coupled receptors, and that this site may provide a target for therapeutic discovery.
J Pharmacol Sci. 2008 Jun; 107(2): 175-80
Ayajiki K, Kimura T, Yamamizu K, Okamura T
To compare the mechanisms underlying mechanical responses to ephedrine and Ephedra herb, a main component of Kakkon-to, in isolated male and female rabbit urinary bladder and urethral strips, responses of isolated strips to the agents were recorded in organ bath systems. Ephedrine and Ephedra herb relaxed the female urinary bladder to the similar extent. These relaxations are reversed to contractions by timolol. In the presence of timolol, ephedrine produced less contraction of urethral strips in the female than those in the male; this contraction was abolished by prazosin. Ephedra herb contracted the female urethra less than that of the male, and the contraction was stronger than that by ephedrine. The contraction caused by Ephedra herb in strips treated with timolol was significantly inhibited by prazosin. The prazosin-resistant contraction of the female urethra was greater than that of the male. Quinacrine, a phospholipase A(2) inhibitor, indomethacin, and AA861, a 5-lipoxygenase inhibitor, inhibited the contraction. The contraction was inhibited by ZK 158252, a leukotriene (LT) B(4)-receptor antagonist. These findings suggest that Ephedra herb contracts the urethra via arachidonic acid metabolites together with alpha(1)-adrenoceptor stimulation. The metabolites produced by 5-lipoxygenase may stimulate LTB(4), but not CysLt(1), receptors. These contractile components induced by Ephedra herb and Kakkon-to might be effective for the treatment of stress urinary incontinence.
Ophthalmology. 2008 Jun 4;
Kaback M, Scoper SV, Arzeno G, James JE, Hua SY, Salem C, Dickerson JE, Landry TA, Bergamini MV,
PURPOSE: To compare the safety and intraocular pressure (IOP)-lowering efficacy of brinzolamide 1%/timolol 0.5% fixed combination with brinzolamide 1% or timolol 0.5% alone in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). DESIGN: Randomized, double-masked, parallel group, multicenter study. PARTICIPANTS: Five hundred twenty-three patients were randomized to the study treatments. METHODS: Patients with OAG or OHT were recruited to the study. Qualifying eyes had IOPs of 24 to 36 mmHg at 8 am and 21 to 36 mmHg at 10 am on 2 eligibility visits after an appropriate washout period from previous treatment. Patients were assigned randomly to either brinzolamide 1%/timolol 0.5%, brinzolamide 1% (Azopt; Alcon Laboratories, Fort Worth, TX), or timolol 0.5%, dosed twice daily and were followed up while receiving therapy for 6 months. At selected sites, additional IOP measurements were performed at 12 pm, 4 pm, and 8 pm during the 2 eligibility visits, at month 3, and at month 6. MAIN OUTCOME MEASURE: Mean IOP. RESULTS: Brinzolamide 1%/timolol 0.5% produced statistically significant and clinically relevant reductions from baseline ranging from 8.0 to 8.7 mmHg, which were statistically and clinically superior to that of either brinzolamide 1% (5.1-5.6 mmHg) or timolol 0.5% (5.7-6.9 mmHg). No safety concerns were identified based on an assessment of ocular and cardiovascular parameters and a review of adverse events. CONCLUSIONS: Brinzolamide 1%/timolol 05% is superior in IOP-lowering efficacy to either brinzolamide 1% or timolol 0.5%.
Eye. 2008 Jun 6;
Martinez A, Sanchez M
ObjectiveTo evaluate bimatoprost/timolol fixed combination (BTFC) vs latanoprost/timolol fixed combination (LTFC) given each evening over the 12-h intraocular pressure (IOP) diurnal curve.MethodsA total of 54 eyes of 54 patients (24 with primary open-angle glaucoma (POAG) and 30 with pseudoexfoliative glaucoma (PXG)) were included in this prospective, randomized, evaluator-masked single centre crossover study. Patients with an IOP of >/=19 mmHg, under treatment with prostaglandin analogues, were randomized to BTFC or LTFC for a 12-week treatment period after a 6-week run-in period on timolol maleate 0.5% (one drop in each eye twice each day). Patients were then switched to the opposite treatment for the second period. Six 12-h IOP curves were recorded for each patient at baseline (under treatment with timolol maleate 0.5% BID), week 6 and 12 for each treatment period.ResultsThe 12-h IOP (mean (SD)) values were 22.0 (1.0) mmHg at baseline, 17.7 (0.8) mmHg on BTFC, and 18.5 (0.8) mmHg on LTFC (P
Topical antiglaucoma medications and lacrimal drainage system obstruction.
Ophthal Plast Reconstr Surg. 2008 May-Jun; 24(3): 172-5
Kashkouli MB, Rezaee R, Nilforoushan N, Salimi S, Foroutan A, Naseripour M
PURPOSE: To evaluate the effect of topical antiglaucoma medications on the lacrimal drainage system. METHODS: In a prospective controlled blind observational case series, 627 eyes of 384 patients (219 males, 165 females) were screened. Data recording (demographics and history taking), allocation in case (on topical antiglaucoma medications) and control (no glaucoma) groups, and examinations (eye examination and dye disappearance test) were performed by a senior ophthalmology resident. Exclusion criteria were epiphora prior to onset of treatment with topical antiglaucoma medication (only for case group), history of long-term use of topical medications (other than antiglaucoma medications in the case group), and previous ocular and periocular disorders. Diagnostic probing and irrigation of the lacrimal drainage system were performed by an oculoplastic surgeon masked to a patient's status as case or control. RESULTS: After exclusion, there were 130 eyes from 98 patients and 280 eyes from 178 patients in the case and control groups, respectively. Case and control groups were matched. There was significantly more lacrimal drainage system obstruction in the case group (26 of 130, 20%) than in the control group (24 of 280, 8.57%) (p = 0.002). Upper lacrimal drainage system obstruction was significantly more in the case group (p = 0.018). Increasing age was associated with significantly more obstruction in the control group only (p = 0.029). Statistically significant obstruction was found in the patients taking timolol + dorzolamide (p = 0.021) and timolol + dorzolamide + pilocarpine (p = 0.017) with a duration of 2 weeks to 156 months. CONCLUSION: Patients taking a combination of topical antiglaucoma medications showed significantly increased risk of developing lacrimal drainage system obstruction. Both total and upper obstruction was significantly more frequent in patients on topical antiglaucoma medications.
Ophthalmic Res. 2008 May 28; 40(6): 298-308
Denoyer A, Ossant F, Arbeille B, Fetissof F, Patat F, Pourcelot L, Pisella PJ
Aim: To evaluate very-high-frequency (VHF) ultrasound imaging as a new method to detect and quantify early corneal epithelium changes induced by chronic exposure to a benzalkonium-chloride-containing antiglaucoma drug. Methods: Timolol preserved with 0.01% benzalkonium chloride solution was applied b.i.d. in 1 eye of 10 rabbits for 56 days. Unpreserved timolol solution was used as control. Ocular surface changes were assessed weekly combining clinical examinations, in vivo 60-MHz ultrasound imaging and ex vivo histological analysis. Results: VHF ultrasound imaging allowed quantitative measurement of corneal epithelium thickness and qualitative imaging of toxic epithelial damage. It revealed significantly decreased epithelial thickness in vivo as early as the 21st day of treatment (40.75 +/- 1.72 mum at D0 vs. 39 +/- 2 at D21, vs. 31.9 +/- 2.98 at D56; p = 0.017 and p = 0.005, respectively). The first clinical changes appeared from the 42nd day of treatment (conjunctival redness, conjunctival staining and corneal staining; D56 compared to D0: p = 0.005, 0.01 and 0.004, respectively) and then correlated with VHF ultrasound data. Epithelial thickness measured with VHF ultrasound was correlated with histological epithelial pachymetry (p < 0.001) and with the corneal damage score assessed with scanning electron microscopy (p = 0.038). Conclusion: VHF ultrasound imaging provided an early in vivo diagnosis of corneal epithelium pathology induced by chronic exposure to a preserved glaucoma drug, before the first clinical evidence of ocular toxicity. It could be a new reproducible method to detect the toxicity of glaucoma medication so that therapy can then be adapted.
Invest Ophthalmol Vis Sci. 2008 May 23;
Quaranta L, Miglior S, Floriani I, Pizzolante T, Konstas A
Purpose. To evaluate the effect of the timolol-dorzolamide fixed combination (TDFC) and latanoprost 0.005% on 24-hour intraocular pressure (IOP), systolic (SBP) and diastolic blood pressure (DBP), and diastolic ocular perfusion pressure (DOPP), in glaucoma (POAG) patients. Setting. Institutional randomized clinical trial Methods. Following a 24-hour assessment without treatment, 27 previously untreated POAG patients were randomized to six weeks' treatment with twice-daily TDFC (08:00 and 20:00) followed by once-daily latanoprost 0.005% (20:00), or vice versa. One eye was analyzed per patient. The mean values of IOP, DBP, SBP and DOPP (difference between DBP and IOP) were recorded at each time point, and the 24-hour data are the mean values of each patient?s measurements over the 24-hour period. The differences between the values of first treatment period and the baseline, and the second treatment period and washout were calculated and analyzed by means of an analysis of variance model that tested the effects of sequence and treatment. Results. Both treatments significantly reduced 24-hour IOP (p
Curr Med Res Opin. 2008 Jun; 24(6): 1755-61
Holló G, Kóthy P
OBJECTIVE: To investigate if combined intraocular pressure (IOP)-lowering medication with travoprost/timolol fixed combination and a carbonic anhydrase inhibitor, brinzolamide, is superior to both travoprost monotherapy and travoprost/timolol fixed-combination therapy in primary open-angle glaucoma and ocular hypertension. METHODS: Following a 4-week wash-out period and using 4-week long treatment periods, 20 primary open-angle glaucoma or ocular hypertension patients were treated with evening travoprost 0.004%, then switched to evening travoprost 0.004%/timolol 0.5% fixed combination, and finally the treatment was combined with adjunctive twice-daily brinzolamide 1% ophthalmic suspension. Both eyes were treated, but only one eye per patient (the eye with the higher mean diurnal IOP at baseline), was evaluated. IOP was measured at 8 a.m., 12 noon and 4 p.m. at baseline and at the end of each treatment period. RESULTS: Mean diurnal IOP (mean (SD)) at baseline was 28.5 (7.3) mmHg which decreased to 22.3 (6.3) mmHg on travoprost, 19.2 (3.4) mmHg on travoprost/timolol fixed combination and 17.3 (3.4) mmHg when the brinzolamide was added to the travoprost/timolol combination (ANOVA, contrast test, p
Ozonation of reverse osmosis concentrate: Kinetics and efficiency of beta blocker oxidation.
Water Res. 2008 Jun; 42(12): 3003-12
Benner J, Salhi E, Ternes T, von Gunten U
Reverse osmosis (RO) concentrate samples were obtained from a RO-membrane system that uses effluents of wastewater treatment plants (WWTP) as feed water for the production of drinking water. A number of different pharmaceuticals (e.g. antibiotics, contrast media, beta blockers) were found in the WWTP effluent as well as in the RO-concentrate. Overall, a concentration factor (feed:concentrate) of approximately 3-4 was measured. Beta blockers (acebutolol, atenolol, bisoprolol, celiprolol, metoprolol, propranolol, timolol) were found in the range of low ng/L to low mug/L. Because metoprolol and propranolol are classified as potentially toxic to aquatic organisms and all beta blocker molecules have moieties, which are reactive towards ozone (amine groups, activated aromatic rings), it was tested whether ozonation can be applied for their mitigation. Rate constants for the reaction of acebutolol, atenolol, metoprolol and propranolol with ozone and ()OH radicals were determined. At pH 7 acebutolol, atenolol and metoprolol react with ozone with an apparent second-order rate constant ( [Formula: see text] ) of about 2000M(-1)s(-1), whereas propranolol reacts with approximately 10(5)M(-1)s(-1). The rate constants for the reaction of the selected compounds with ()OH radicals were determined to be 0.5-1.0x10(10)M(-1)s(-1). Experiments with RO concentrate showed that an ozone dose of only 5mg/L resulted in a quantitative removal of propranolol in 0.8s and 10mg O(3)/L oxidized 70% of metoprolol in only 1.2s. Tests with chlorinated and non-chlorinated WWTP effluent showed an increase of ozone stability but a decrease of hydroxyl radical exposure in the samples after chlorination. This may shift the oxidation processes towards direct ozone reactions and favor the degradation of compounds with high [Formula: see text] .