Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An investigation was carried out to determine the mechanism by which MK-507 (L-671,152), a water-soluble inhibitor of human carbonic anhydrase II in vitro, reduces intraocular pressure when applied topically to monkey eyes. Intraocular pressure, tonographically measured outflow facility, and fluorophotometrically determined aqueous humor flow were measured before and after therapy in eight normal cynomolgus monkeys. Fifty microliters of 2% MK-507 was instilled in one eye and diluent in the contralateral eye. Baseline values for intraocular pressure, outflow facility, and aqueous humor flow were similar in the drug-treated and diluent-treated control eyes. After therapy, intraocular pressure was significantly (P less than .05) reduced from 1 to 7 hours (eg, 14.0 +/- 1.0 and 15.9 +/- 0.9 mm Hg [mean +/- SEM], treated and control eyes, respectively, at 3 hours). Outflow facility was not significantly (P greater than .40) changed at 3 hours, and aqueous humor flow measured over 5 hours was significantly (P less than .05) reduced (38%) in treated (0.9 +/- 0.1 microL/min) as compared with control eyes (1.5 +/- 0.1 microL/min). The results suggest that MK-507 reduces intraocular pressure by decreasing aqueous humor production.
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PMID:MK-507 (L-671,152), a topically active carbonic anhydrase inhibitor, reduces aqueous humor production in monkeys. 192 60

It was reported that 8-Hydroxycarteolol (8-OH CA), the major metabolite of carteolol hydroxychloride (CA), has a slightly different pharmacological effect from CA. We studied the reduction of intraocular pressure (IOP) on a single eyedrop application of 8-OH CA in albino and pigmented rabbit eyes. To determine the characteristic of 8-OH CA and CA, we investigated the binding ability of these drugs to synthetic melanin. In the present study, topically applied 2% CA did not significantly decrease IOP in albino and pigmented rabbit eyes. Topically applied 0.01, 0.05, 0.1 and 1.0% 8-OH CA significantly decreased the IOP of albino rabbit as did 0.1 and 1.0% 8-OH to pigmented rabbit eyes. The maximum reduction of IOP was 3.5 +/- 0.33 mmHg (mean +/- SEM) in albino rabbit and 3.0 +/- 0.45 mmHg (mean +/- SEM) in pigmented rabbit. Maximum IOP reduction was obtained after 30 min. from topical application in albino rabbit, but in pigmented rabbit after 1 hour or later. Our binding studies to melanin show that the melanin binding ability is less for 8-OH CA than for CA at any concentrations. These results may indicate that lower concentrations of topically applied 8-OH CA profoundly reduce IOP compared to CA, and 8-OH CA has less effect on melanin than CA.
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PMID:[Effect of topical 8-hydroxy carteolol on intraocular pressure and melanin granules]. 195 Aug 31

The effects of topically applied bunazosin hydrochloride, a recently developed highly selective alpha 1-adrenergic antagonist, on intraocular pressure, pupillary diameter, aqueous protein concentration, anterior chamber volume, aqueous flow rate and tonographic outflow facility were investigated in eight normal human volunteers. A single application of 0.1% bunazosin hydrochloride caused a significant unilateral reduction in the intraocular pressure from 30 minutes through 4 hours after the application, with a maximum decrease of 2.0 +/- 0.5mmHg (mean +/- SEM) below the contralateral control eyes at 2 hours post-application. Neither pupillary diameter, anterior chamber volume nor outflow facility was affected by the drug application. Both aqueous protein concentration measured with a flare-cell meter and aqueous flow rate determined by fluorophotometry were unaltered. The mechanism of intraocular pressure reduction appears to be an increase in uveoscleral outflow and/or a decrease in episcleral venous pressure.
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PMID:[Changes in intraocular pressure and aqueous humor dynamics of normal human eyes after topical application of bunazosin hydrochloride]. 197 23

Measurements of pulsatile ocular blood flow (POBF) have been recorded in a group of healthy, ocular normotensive volunteers and ocular hypertensive patients recruited from outpatients. Use of a pneumotonometric probe linked to a Langham ocular blood flow system enabled readings of intraocular pressure and its variation with heart rate (ocular pulse) to be taken in erect and supine positions. Pulsatile ocular blood flow was calculated from these values by means of the pressure-volume relationship previously described for living human eyes. Assumption of the supine posture was accompanied by a significant rise in intraocular pressure; in normal eyes (mean, with SEM) (3.1 (0.4) mmHg, p less than 0.0001) and to a greater extent in ocular hypertensive eyes (4.7 (0.6) mmHg, p less than 0.0001). The POBF did not differ significantly between normotensive and ocular hypertensive groups in either the erect or supine postures. In both groups, however, assumption of the supine posture was accompanied by a significant fall in POBF (normals: -121 (21) microliters/min, p less than 0.0001; ocular hypertensives: -75 (16) microliters/min, p less than 0.0002). These reductions in POBF represent decrements of 27.5 (3.0)% and 17.1 (3.8)% respectively. Pulsatile ocular blood flow is reduced in the supine posture, and this may result in tissue hypoxia in subjects at risk of developing glaucoma. A companion paper describes the measurement of POBF in a group of patients with chronic open angle glaucoma treated with topical timolol 0.25%.
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PMID:Postural studies in pulsatile ocular blood flow: I. Ocular hypertension and normotension. 199 45

The pulsatile ocular blood flow (POBF) has been recorded in 15 patients with chronic open angle glaucoma. Measurements were performed during regular treatment with timolol 0.25% eyedrops, two weeks after withdrawal of this treatment, and then a further two weeks after its reinstitution. Readings were taken with subjects in both the erect and supine positions by means of a pneumotonometric probe to measure intraocular pressure (IOP), linked to a Langham ocular blood flow system. Assumption of the supine posture was associated with a significant increase in IOP in all phases of the study. Treatment with timolol lowered the mean IOP in comparison with the untreated phase (-4.4 (SEM 0.6) mmHg, p less than 0.001) but had no effect on the postural change. A significant reduction in POBF was recorded on assumption of the supine posture (-66 (SEM 18) microliters/min, p less than 0.001), representing a mean decrement of 19%. However, there were no significant differences in POBF between treated and untreated phases of the study. Comparison of the values obtained in patients with glaucoma (COAG) after withdrawal of treatment with those in subjects with ocular hypertension revealed that there was no significant difference in intraocular pressure between the two groups. However, both POBF (-68 (SEM 29) microliters/min) and the pulse amplitude of the intraocular pressure (ocular pulse: -0.45 (SEM) 0.14 mmHg) were significantly lower in the COAG patients. Pulsatile ocular blood flow is significantly lower in patients with chronic open angle glaucoma. Furthermore, the POBF and the postural response of these patients is not improved by the use of topical timolol therapy.
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PMID:Postural studies in pulsatile ocular blood flow: II. Chronic open angle glaucoma. 199 46

Effects of topical administration of a single dose of timolol maleate on intraocular pressure (IOP) and pupil diameter were evaluated in normotensive eyes of 11 clinically normal dogs over 12 hours (7:00 AM to 7:00 PM). Mean (+/- SEM) normal IOP was 15.5 (+/- 1.1) mm of Hg and diurnal fluctuation was observed, with the highest IOP seen in the morning. Mean normal pupil diameter was 8.5 (+/- 0.3) mm. Topical treatment with 0.5% timolol resulted in reduction of IOP in the treated and nontreated eyes. Mean reduction of IOP in the treated eye was 2.5 mm of Hg, a reduction of 16.1%, with maximal reduction of 3.7 mm of Hg. Mean reduction of IOP in the nontreated eye was 1.4 mm of Hg, a reduction of 9.0%. The treated eye had reduced pupil diameter at 30 minutes after treatment, which persisted throughout the 12 hours of the study. Mean reduction of pupil diameter in the treated eye was 2.9 mm, a reduction of 34.1%. In addition, a contralateral effect on pupil diameter was seen in the nontreated eye, with mean reduction of 1.2 mm, a reduction of 14.1%. Topical administration of timolol maleate resulted in reduction of IOP and pupil diameter in treated and contralateral eyes, thus supporting the use of timolol for treatment of glaucoma in dogs. Miosis indicates possible beta-adrenergic inhibition or alpha-adrenergic activation of the sphincter muscle. beta-Adrenergic blockade would then result in miosis.
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PMID:Effects of topical administration of timolol maleate on intraocular pressure and pupil size in dogs. 203 17

Effects of topical administration of a single dose of timolol maleate, a nonselective beta-adrenergic blocking agent, on intraocular pressure (IOP) and pupil diameter were evaluated in the normotensive eyes of 10 clinically normal cats over 12 hours. Mean (+/- SEM) normal IOP was 17.1 (+/- 1.1) mm of Hg and diurnal fluctuation was observed, with the highest IOP seen in the evening. Mean (+/- SEM) normal pupil diameter was 10.1 (+/- 0.5) mm. Topical treatment with 0.5% timolol resulted in reduction of IOP in treated and nontreated eyes. This effect was time-dependent and was first observed at 6 hours after treatment. Mean reduction of IOP was 22.3% in the treated eye and 16.3% in the nontreated eye. The treated eye had reduced pupil diameter at 30 minutes after treatment, and miosis persisted throughout the 12 hours of the study. Mean reduction of pupil diameter was 38.7%. A contralateral effect on pupil diameter was not seen in the nontreated eye. Topical administration of timolol maleate results in a reduction of IOP in treated and contralateral eyes, which supports the use of timolol for treatment of glaucoma in cats. In addition, the treated eye becomes miotic. This effect may indicate beta-adrenergic inhibition or alpha-adrenergic activation of the iris sphincter muscle. beta-Adrenergic blockade would then result in miosis.
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PMID:Effects of topical administration of timolol maleate on intraocular pressure and pupil size in cats. 203 18

Effects of topical administration of a single dose of 2% pilocarpine on intraocular pressure (IOP) and pupil diameter were evaluated in normotensive eyes of 10 clinically normal cats over 12 hours. Mean (+/- SEM) normal IOP was 17.1 (+/- 1.1) mm of Hg and, diurnal fluctuation was observed, with the highest IOP seen in the evening. Mean (+/- SEM) normal pupil diameter was found to be 10.1 (+/- 0.5) mm. Topical treatment with pilocarpine resulted in reduction of IOP in treated and nontreated eyes. This effect was time-dependent and was first observed at 4 hours after treatment. Mean reduction of IOP was 15.2% in the treated eye and 9.3% in the nontreated eye. The treated eye had reduced pupil diameter at 30 minutes after treatment, and miosis persisted throughout the 12 hours of the study. Mean reduction in pupil diameter was 28.5% in the treated eye and 14.2% in the nontreated eye. Topically administered pilocarpine results in reduction of IOP and pupil diameter in treated and contralateral eyes, which supports the use of pilocarpine for treatment of glaucoma in cats.
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PMID:Effects of topical administration of 2.0% pilocarpine on intraocular pressure and pupil size in cats. 203 19

Atrial natriuretic factor (ANF) concentration in the aqueous humor (AH) was studied in rabbits with experimental glaucoma induced by injecting alpha-chymotrypsin into the posterior chamber. In normal rabbit eyes, the ANF concentration in AH was 3.1 +/- 1.2 pg/ml (mean +/- SEM; n = 12), ranging from 0 to 5.8 pg/ml, whereas it was significantly higher in AH from glaucomatous rabbit eyes, being 81.0 +/- 9.8 pg/ml (n = 12). These findings were correlated with intraocular pressure (IOP), which was 13.0 +/- 2.4 mmHg (n = 12) in normal rabbit eyes and significantly greater in glaucomatous eyes: 24.4 +/- 3.0 mmHg (n = 12). Our data indicate that enhanced ANF release in AH during experimental glaucoma may play an important physiological role in modulating IOP.
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PMID:Immunoreactive atrial natriuretic factor in aqueous humor: its concentration is increased with high intraocular pressure in rabbit eyes. 214 92

We investigated the dose-response and reproducibility of the intraocular pressure-lowering effect of MK-927 in ocular hypertensive patients. Patients were enrolled until at least 8 "marked responders" (peak reduction in intraocular pressure comparing the MK-927-treated eye with the placebo-treated eye greater than or equal to 6 mm Hg) and 7 "mild responders" (peak reduction in intraocular pressure comparing the MK-927-treated eye with the placebo-treated eye less than or equal to 3 mm Hg) were identified. In part A, 27 patients received one drop of 2% MK-927 in one eye (baseline mean +/- SEM intraocular pressure, 28.0 +/- 1.0 mm Hg) and placebo in the contralateral eye. Intraocular pressure was measured at baseline and 1, 2, 3, 4, and 6 hours. Maximum reduction in intraocular pressure was 4.0 +/- 0.8 mm Hg at 3 hours, with a duration of 4 hours. Ten patients were identified as marked responders and 7 as mild responders. In part B, 8 of the marked responders entered a four-period crossover study and received 2%, 0.5%, and 0.125% MK-927 and placebo in the same treated eye as in part A, and placebo in the contralateral eye. The 7 mild responders in part C received 2% MK-927 in a similar fashion as in part A. MK-927 in concentrations of 0.125% and 0.5% had little or no effect on intraocular pressure in patients with a marked response to 2% MK-927. Within-patient variability in peak response to single doses of 2% MK-927 was substantial (coefficient of variation of 0.3 and 0.5 for marked responder and mild responder groups, respectively.
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PMID:MK-927, a topical carbonic anhydrase inhibitor. Dose response and reproducibility. 219 May 47


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