Effect of non-steroidal anti-inflammatory ophthalmic solution on intraocular pressure reduction by latanoprost in patients with primary open angle glaucoma or ocular hypertension.

AIM: To investigate the effects of a non-steroidal anti-inflammatory drug (NSAID) ophthalmic solution on latanoprost induced intraocular pressure (IOP) reduction in glaucoma patients. METHODS: Examination was conducted on 16 eyes of 16 glaucoma patients who had been given only latanoprost for at least 6 weeks. The NSAID ophthalmic solution, sodium 2-amino-3-(4-bromobenzoyl) phenylacetate sesquihydrate, was additionally given for 12 weeks into one eye (NSAID group), while sodium hyaluronic acid ophthalmic solution was administered into the other eye (control group) in a double masked fashion. The IOP measurement was performed before the start of additional administration of ophthalmic solutions, 2, 4, 6, 8, 10, and 12 weeks after the start of additional administration, and 2, 4, and 6 weeks after discontinuing additional administration. RESULTS: No significant difference was observed in the IOPs before additional administration of ophthalmic solution between the NSAID group and the control group. Following the additional administration of ophthalmic solution, IOP in the NSAID group was consistently higher than that in the control group, and a maximum difference in IOP between the two groups was 1.08 (SD 1.75) mm Hg (p = 0.03). This trend was observed even after additional administration was discontinued. CONCLUSION: NSAID ophthalmic solution may partly affect IOP reduction by latanoprost.

Prostaglandins and cystoid macular edema.

This review discusses the roles and interactions of prostaglandins and other possible chemical mediators in cystoid macular edema. Prostaglandins have been studied as a potential causative factor of cystoid macular edema following cataract/intraocular lens surgery. The authors' hypothesis and data with regard to the mechanisms of postoperative cystoid macular edema and other inflammatory conditions are presented. The effects of nonsteroidal anti-inflammatory drugs, which are antagonists of prostaglandin biosynthesis, on postoperative inflammatory conditions including cystoid macular edema are also reviewed. Lastly, a mechanism for the induction of cystoid macular edema by anti-glaucoma eyedrops, including prostaglandin analogs is proposed. The results from two clinical trials recently conducted by the authors suggest that the preservative rather than the active ingredient is the causative factor.

Effect of indomethacin on the injection-abortion interval of 15(S) 15 methyl PGF2 alpha-induced mid-trimester abortions--a randomized study.

There have been conflicting reports on the effect of non-steroidal anti-inflammatory drugs on the abortifacient effect of prostaglandins. The efficacy of intra-amniotic 1.5 mg 15(S) 15 methyl PGF2 alpha (15 me PGF2 alpha) in terminating mid-trimester pregnancy in 10 subjects has been compared with the effect of the same medication given to 10 others who had had indomethacin 25 mg and 50 mg orally three and one hour before the PG administration. In the subjects who had the PG analogue only the injection-abortion interval was 17.0 hours. This was significantly shorter (P less than 0.01) than in those who had also received indomethacin (25.4 hours).

Central action of low-molecular weight polyphloretin phosphate fraction in rats.

The central effects of a low-molecular weight fraction of polyphloretin phosphate (PPP) with molecular weight about 4600 were studied using several behavioural tests in animals (Lat's test, open-field test, hold-board test, irritability, spontaneous motor activity), chlorpromazine-induced catalepsy test, body temperature measurements, hexobarbital-induced sleep duration, reaction to thermal painful stimulus, measurements of arterial blood pressure, heart rate and respiratory rate. The activity of prostaglandin synthetase was determined also in the microsomes of bovine hypothalamic cells in vitro. Using some of the above tests the effect of PPP was studied on the central action of prostaglandins F2 alpha and E2 (PGF2 alpha and PGE2). PPP was administered intraventricularly (i.c.v.) in various doses (doses producing the lowest pharmacological effect in a given test) 10 minutes before i.c.v. administration of these prostaglandins in doses of 1 or 10 microgram. It was shown that PPP (low-molecular weight fraction) injected into the lateral cerebral ventricle of the rat exerted a biological effect on the central nervous system manifesting itself as behaviour changes in the tests used, and as changes of the arterial blood pressure. PPP i.c.v. antagonized certain central effects of PGF2 alpha and PGE2. The degree of inhibition of various prostaglandins differed in relation to the test used and was somewhat stronger in the case of PGF2 alpha.

alpha-Methyl-p-tyrosine inhibits latanoprost-induced melanogenesis in vitro.

The PGF2alpha derivative, latanoprost, is a recent anti-glaucoma drug that has been reported to induce a discrete incidence of increased iris pigmentation in men. The present experiments were made in order to study whether this phenomenon could be influenced by the tyrosinase inhibitor, alpha-methyl-p-tyrosine. Melanin content, melanin production and tyrosinase activity of cultured uveal melanocytes derived from irides of brown or brown-blue color were measured after adding latanoprost at different molar concentration with or without alpha-methyl-p-tyrosine (10(-5)m). It was shown that latanoprost stimulated melanin content, melanin production and tyrosinase activity in a molar range between 10(-7) and 10(-5)m in uveal melanocytes derived from irides of both brown and brown-blue color. The effect seemed to be more pronounced in melanocytes derived from irides of brown-blue color. The adding of alpha-methyl-p-tyrosine completely prevented latanoprost-induced stimulation of melanin production in uveal melanocytes derived from irides of both colors. These results suggest that latanoprost-induced stimulation of melanin production, follows the metabolic pathway involving tyrosinase activity and may be relevant for the therapeutic application of latanoprost in glaucoma in order to reduce its side-effect resulting in increased iris pigmentation.

Comparison between isopropyl unoprostone and latanoprost by prostaglandin E(2)induction, affinity to prostaglandin transporter, and intraocular metabolism.

The pharmacological differences between isopropyl unoprostone (referred to as unoprostone) and latanoprost, concerning their induction of endogenous prostaglandin E(2)(PGE(2)) and affinity to a human prostaglandin transporter (PGT), were investigated. Freshly dissected bovine iris tissues were incubated with major intraocular metabolites of unoprostone, M1 and M2, acid of latanoprost, or PGF(2 alpha), and PGE(2)induction was measured. Affinities of M1, M2, latanoprost, acid of latanoprost, and PGF(2 alpha)to PGT molecule were measured using PGT-cDNA transfected HeLa cells by an isotopic influx assay.(3)H-unoprostone was incubated with freshly prepared serum, aqueous humor, or frozen stored fetal bovine serum (FBS), and the radioactivity of supernatants was measured to investigate their metabolism of(3)H-unoprostone.M2, acid of latanoprost, and PGF(2 alpha)significantly increased a release of PGE(2)compared with the control. 10 microM indomethacin completely inhibited PGE(2)induction by acid of latanoprost and PGF(2 alpha), while 100 microM indomethacin was required to inhibit PGE(2)induction completely by M1 and M2. Unoprostone, M1, M2, and latanoprost showed little affinity to PGT, while acid of latanoprost had an affinity to PGT. Freshly prepared serum and aqueous humor metabolized unoprostone, but frozen stored FBS did not. The release of endogenous PGE(2)may play an important role of action by means of PG analogs, and differences in indomethacin-related inhibition of PGE(2)release and in affinities to PGT may in part cause their different actions.

Vascular smooth muscle activity of 7-oxa-13-prostynoic acid.

The effects of 7-oxa-13-prostynoic acid (7-OPA), alone and as an antagonist of PGE2 and PGF2alpha, were investigaed in isolated rabbit aortic and canine renal arterial (diameter approximentaly 0.5 mm) strips. 7-OPA caused contractions in both preparations; threshold concentrations were 3- to 10-fold higher than the PGs and maximum contraction was 50-60%. In concentrations of 10(-5) M, 7-OPA inhibited contractions by PGF2alpha and PGE2. The same concentration of 7-OPA did not inhibit norepinephrine-induced contractions. These data indicate that 7-OPA is a partial agonist of PG receptors and produces its antagonism of PGE2 and PGF2alpha by that mechanism.