Phenyl-substituted prostaglandins: potent and selective antiglaucoma agents

Resul, Bahram; Stjernschantz, Johan; No, Kiyo; Liljebris, Charlotta; Selen, Goeran; Astin, Maria; Karlsson, Maritha; Bito, Laszlo Z.

doi:10.1021/jm00054a008

Cited by 128 publications

(72 citation statements)

References 9 publications

(16 reference statements)

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“…Elevated intraocular pressure (IOP) is a primary risk factor for glaucomatous progression, and lowering IOP has been proven effective in modifying the progressive damage [2] . Prostaglandin analogues are the most potent of currently available ocular hypotensive medications [3][4][5][6] . Introduced in 1996, latanoprost was the first prostaglandin F 2 ␣ analogue to become available worldwide.…”

Section: Introductionmentioning

confidence: 99%

Systematic Review of Intraocular Pressure-Lowering Effects of Adjunctive Medications Added to Latanoprost

2009

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Objective: To evaluate the intraocular pressure (IOP)-lowering effects of adjunctive medications when added to 0.005% latanoprost taken once daily. Methods: Pertinent publications were identified through systematic searches of PubMed, Embase, and the Cochrane Controlled Trials Register. Randomized clinical trials with over 85% of patients presenting with primary open-angle glaucoma or ocular hypertension who were treated with the combination treatment of latanoprost were selected. The pooled additional IOP-lowering effects at 1–3 months after a run-in phase of at least 2 weeks on 0.005% latanoprost once daily were calculated using the random effects model. Results: Nine randomized clinical trials were included. The mean pooled IOP reductions were 3.3 mm Hg (95% CI: 2.1–4.5) at trough and 4.4 mm Hg (95% CI: 3.4–5.4) at peak when adding 0.5% timolol once daily, 2.6 mm Hg (95% CI: 1.9–3.3) at trough and 3.8 mm Hg (95% CI: 2.5–5.2) at peak when adding 0.1/0.15% brimonidine twice daily, 2.6 mm Hg (95% CI: 1.7–3.4) at trough and 3.1 mm Hg (95% CI: 2.6–3.6) at peak when adding 2% dorzolamide twice daily, 2.4 mm Hg (95% CI: 2.0 –2.8) at trough and 2.7 mm Hg (95% CI: 2.2–3.2) at peak when adding 0.5% timolol twice daily, and 2.8 mm Hg (95% CI: 1.5–4.1) at trough and 1.8 mm Hg (95% CI: 1.2–2.3) at peak when adding 1% brinzolamide twice daily. Conclusions: The addition of brimonidine, dorzolamide, timolol, or brinzolamide can further lower IOP in eyes being treated with latanoprost. Timolol 0.5% once daily might be the most effective adjunctive medication.

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Section: Introductionmentioning

confidence: 99%

Systematic Review of Intraocular Pressure-Lowering Effects of Adjunctive Medications Added to Latanoprost

2009

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“…The PGF 2a prostaglandins, a kind of the most effective antiglaucoma drugs at present, attracted synthetical chemists' and medicinal chemists' research interest [1][2][3][4]. The aim of the present work of our research group was to search for a convenient and cheap strage to synthesize this kind of prostaglandins.…”

Section: Discussionmentioning

confidence: 99%

Crystal structure of (±)-(2β-carboxyl-3α-hydroxy-5β-chlorocyclopent- 1α-yl)acetic acid, δ-lactone, C8H9ClO4

Xiong¹,

Liu²,

Zheng³

et al. 2008

Zeitschrift Für Kristallographie - New Crystal Structures

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Source of materialThe mixture of the compound 5-chloro-2-oxo-bicycle[2.2.1] heptan-7-oic acid (1 mmol) and m-chloroperoxybenzoic acid (1 mmol) was stirred in dichloromethane (20 ml) for overnight at room temperature followed by column chromatography, and then the title compound was afforded. Crystals appropriate for diffraction data collection were obtained by slow evaporation of an etheyl actate solution at room temperature for 48 hours. Experimental detailsAll H atoms were positioned geometrically and allowed to ride on their parent atoms at distances of d(C-H) = 0.97 or 0.98 Å with U iso = 1.5 Ueq(parent atom). DiscussionThe PGF 2a prostaglandins, a kind of the most effective antiglaucoma drugs at present, attracted synthetical chemists' and medicinal chemists' research interest [1][2][3][4]. The aim of the present work of our research group was to search for a convenient and cheap strage to synthesize this kind of prostaglandins. The title compound was an important intermediate which decided the conformation of the pentacyclo in the prostaglandins structures. In the title crystal structure, the hepta-lactonecycle shows a boat conformation. In the C2−C3−C4−C5−C6 ring, the future pentacyclo in the prostaglandins structures, the C1−C2−C3−O2 torsion angle of −160.4(5)°describes a trans-C2, C3 configuration; the C1−C2−C6−C7 torsion angle of 166.6(5)°describes the trans-C2, C6 configuration; and then, the Cl1−C5−C6−C7 torsion angle of −159.7 (4)°suggests the trans-C5, C6 configuration.

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“…L ong-term treatment with prostaglandins such as PGE 2 , PGF 2a and latanoprost (13,19, -isopropyl ester) a new drug for glaucoma treatment (Stjernschantz & Resul 1992;Resul et al 1993;Stjernschantz & Alm 1996) has been shown to induce increased iridial pigmentation in monkeys (Selén et al 1997). Similar changes have also been seen in patients with heterochromic eye colour during chronic treatment with latanoprost (Wistrand et al 1997), and with isopropyl unoprostone, another PGF 2a analogue (Yamamoto & Kitazawa 1997).…”

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confidence: 90%

Latanoprost‐induced increase of tyrosinase transcription in iridial melanocytes

Stjernschantz

Ocklind

Wentzel³

et al. 2000

Acta Ophthalmologica Scandinavica

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ABSTRACT.Purpose: Latanoprost, the active principle of Xalatan R eye drops, has been shown to cause increased iridial pigmentation as a side-effect in some patients. The purpose of the present study was to investigate whether latanoprost affects tyrosinase, the rate limiting enzyme in melanogenesis, at the gene transcription level in the iridial melanocytes. Methods: Four cynomolgus monkeys were treated unilaterally with 3 or 11 mg latanoprost once daily for 10 days. The contralateral eye received the vehicle only. Tyrosinase mRNA was visualized by in situ hybridization using radiolabelled riboprobes. The transcription of tyrosinase was also studied in vitro using cultivated human iridial melanocytes. Tyrosinase RNA was quantified by Northern blotting. Results: In the monkeys transcription of tyrosinase was found to be increased in iridial melanocytes of the treated eyes compared to the control eyes. Increased transcription of tyrosinase was in addition found in the iridial pigment epithelium and in melanocytes of the anterior choroid. Latanoprost was also found to increase the transcription of tyrosinase in melanocytes isolated from at least one human eye. Conclusions: Although the tyrosinase enzyme has to undergo complex posttranslational modification to become biologically active, which we have not studied, it appears that latanoprost treatment may increase the transcription of the tyrosinase gene in some individuals, consistent with increased melanogenesis in the iridial melanocytes leading to darker eye colour.

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Phenyl-substituted prostaglandins: potent and selective antiglaucoma agents

Cited by 128 publications

References 9 publications

Systematic Review of Intraocular Pressure-Lowering Effects of Adjunctive Medications Added to Latanoprost

Systematic Review of Intraocular Pressure-Lowering Effects of Adjunctive Medications Added to Latanoprost

Crystal structure of (±)-(2β-carboxyl-3α-hydroxy-5β-chlorocyclopent- 1α-yl)acetic acid, δ-lactone, C8H9ClO4

Latanoprost‐induced increase of tyrosinase transcription in iridial melanocytes

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