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Query: UMLS:C0595921 (intraocular pressure)
 11,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors studied the relation between physicochemical properties and lowering of intraocular pressure (IOP) after topical application to rabbit in a series of 5-acylimino- and related imino-substituted analogs of methazolamide (Compound 4). All had Ki vs. carbonic anhydrase C of about 10(-8) M. The parent, methazolamide (5-acetyl) does not lower IOP, in contrast to the 5-CF3 acetyl compound (Compound 28). The 5-propionyl compound (6) unexpectedly was 3 times more water soluble than methazolamide and had 10 times greater CHCl3-buffer partition. The in vivo transcorneal permeability constant was 6 times greater than methazolamide. One hour after 1 drop of a 2% suspension of Compound 6, anterior aqueous concentration (in micromolar) was 69 (for methazolamide, 8), posterior aqueous was 19 and ciliary process was 17. IOP dropped 2.2 mm Hg and returned to normal in 4 hr. Other compounds in the series showed varying degrees of activity, ranging from Compound 28, which elicited an IOP fall of 3.5 mm Hg, to Compound 7, (n-pentyryl), for which the fall was 1.3 mm Hg. Also studied are substitutions for CH3 on the ring N at position 4. There are multiple criteria for in vivo activity; a major factor is the balance between water and lipid solubility. The methazolamide analogs are compared with benzothiazole-2-sulfonamides, another class under investigation as topical carbonic anhydrase inhibitors designed to treat glaucoma.
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PMID:Ocular pharmacology of methazolamide analogs: distribution in the eye and effects on pressure after topical application. 310 16

Some biochemical factors of the iris-ciliary body of the rabbit have been examined for effects induced by water-soluble marihuana-derived material (MDM). Adenylate cyclase activity and sensitivity to beta-adrenergic agonists were unchanged, as measured 4 hours after MDM administration in vivo. Magnesium-dependent and anion-sensitive, but not sodium-potassium, ATPase activities were inhibited 6 hours after MDM administration in vivo, although they were unaffected by in vitro incubation. Topical administration of a potent substance P antagonist had no effect on the time course or magnitude of intravenous MDM-induced ocular effects in rabbit. Intravenously administered sugars antagonized the effects of MDM on intraocular pressure. A variety of drugs which display a range of biochemical effects varying from beta-adrenergic receptor agonism, to alteration of glycoprotein residues were employed. None of the agents employed, ranging from cAMP modifiers to protein synthesis blockers, had any effect on the MDM-induced response. It is apparent that the mechanism underlying the ocular hypotensive effect of MDM does not reside in mediation through adenylate cyclase, ATPase or substance P, but rather through a mechanism mediated by terminal sugar moieties on the molecule. The data suggest that modification of the surface membrane glycoprotein residues on the ciliary epithelium can induce marked alterations in aqueous humor flow rate.
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PMID:Marihuana-derived material: biochemical studies of the ocular responses. 316 May 44

Chick embryos were injected on the fifth day of incubation with 75 ng cis-diamminedichloroplatinum II (cisplatin) and killed at daily intervals. Bilateral microphthalmia appeared in 88% of the surviving embryos; the decrease in eye size was noticeable 2 or 3 days after injection. Coinciding with this, macroscopic, histological, and ultrastructural changes started to appear in the ciliary body: ciliary processes failed to form and the cells in the inner layer of the ciliary epithelium underwent degenerative changes. Changes in the retina appeared somewhat later. Despite the decreased growth rate of the whole eye the neural layer of the retina continued to grow rapidly; as a result, it formed numerous folds and acquired a glandular appearance. In the most severe cases the rapidly growing retina would invade the ciliary region and replace completely the degenerated inner layer of the ciliary epithelium. It has been shown by previous authors that intraocular pressure is a determinant of eye expansion and also that the secretion of water and ions by the ciliary epithelium is important for the maintenance of that intraocular pressure. On this basis, our results are interpreted as indicating that the primary lesion induced by cisplatin was in the ciliary epithelium and that microphthalmia was the consequence of decreased pressure. It is also concluded that the retinal changes were due to the fact that the retina continued to grow despite the lack of expansion of the eye as a whole.
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PMID:Experimental induction of microphthalmia in the chick embryo with a single dose of cisplatin. 335 62

Nine female and 2 male hyperprolactinaemic patients (plasma prolactin levels averaging 180-420 ng/ml) were subjected to measurements of intraocular pressure (IOP) either under basal conditions or after water load in comparison with 5 healthy volunteers. Basal values of IOP in hyperprolactinaemic patients were 37.8% higher than those of controls. Moreover, after water load hyperprolactinaemic patients showed a sustained increase in IOP that reached values of pathological significance. These results suggest that prolactin may contribute to the hormonal regulation of IOP in humans.
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PMID:Hyperprolactinaemia increases intraocular pressure in humans. 343 24

Xylazine is an agent frequently used in combination with ketamine to anesthetize rabbits. Xylazine is also related pharmacologically to clonidine, a relatively selective alpha 2-agonist. In the present studies, xylazine was examined for its effects on intraocular pressure (IOP) and pupil diameter (PD) in rabbits, cats and monkeys and on noradrenergic function in the cat nictitating membrane (CNM) preparation. Topical and unilateral administration of xylazine (1.0 mg) lowered IOP bilaterally in normal, unanesthetized rabbits, cats and monkeys and caused unilateral miosis in rabbits and cats. These ocular effects of xylazine were attenuated in superior cervical ganglionectomized (SX) cats and rabbits. In addition, intra-arterially administered xylazine (10, 33 and 100 micrograms) produced dose-related inhibition of contractions of the CNM elicited by electrically stimulating the pre- and postganglionic sympathetic trunks without altering the response to i.a. norepinephrine (10 micrograms). These data suggest that ocular effects of xylazine are mediated, in part, by alteration of sympathetic neuron function. Xylazine suppressed ocular hypertension induced by water loading and IOP recovery rate following hypertonic saline infusion in rabbits suggesting that aqueous flow was inhibited. Topical pretreatment with 0.05 mg of timolol caused potentiation of the ocular hypotensive response to 0.05 mg of xylazine in rabbits. These results indicate that xylazine lowers IOP, in part, by suppressing sympathetic neuronal function which causes a reduction in aqueous flow. The augmented response to timolol and xylazine, as compared with either agent alone, suggests a rational basis for combining a prejunctionally active agent with a postjunctionally active one.
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PMID:The ocular effects of xylazine in rabbits, cats, and monkeys. 350 99

Both anticoagulants (heparin and streptokinase) and non-steroidal anti-inflammatory compounds (aspirin and indomethacin) were used against a water-soluble derivative of marihuana, MDM. While the anticoagulants had no effect on the ocular effects of MDM, both aspirin and indomethacin altered the time course and effected the MDM-induced reduction of intraocular pressure. The usual initial hypertensive effect of intravenous MDM was eliminated and the later intraocular pressure fall occurred earlier as well as being inhibited by about 35 to 50%. Assay for prostaglandins revealed that intravenous MDM (3.86 micrograms) caused a marked rise in PGE2 concentration of the aqueous humor and iris-ciliary body during the first hour or two after administration of MDM, but normal values occurred at 4, 6, and 8 hours when the intraocular pressure is reduced by up to 60%. Following intravitreal MDM (0.002 microgram), however, the PGE2 levels remained unchanged over 24 hours, despite the induction of a fall in intraocular pressure between 14 and 18 hours which lasts for many hours. Prostaglandin appears to be involved in the hypertensive phase of intraocular pressure change after intravenous MDM injection; and, while the fall in intraocular pressure may contain a component partially mediated by prostaglandins, there is no evidence that intravitreal MDM induces any effect on prostaglandin levels. The involvement of prostaglandins, therefore, in the mediation of MDM-induced ocular hypotensive effects is apparently small.
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PMID:Prostaglandin involvement in the responses of the rabbit eye to water-soluble marihuana-derived material. 356 47

In a group of 46 patients with moderately elevated intraocular pressure (22-30 mmHg), signs of early glaucoma were found in half of them after a follow-up of 5-7.5 years. Most of the patients showed only a small increase in optic disc cupping revealed by stereophotography. Initial IOP higher than 25 mmHg, large pressure differences between the two eyes, large diurnal pressure variation, occurrence of pseudoexfoliation, pressure drop of more than 8 mmHg after topical epinephrine, and a pressure rise of more than 4 mmHg after water loading were more frequent in the group of patients who developed signs of glaucoma. Age, a positive family history, occurrence of cardiovascular disease, and the cup/disc ratio did not differ in the two groups of patients. The pilocarpine test and steroid provocation had no predictive value. Surprisingly, there was a small drop of pressure after topical steroids in 6 of the 8 patients with pseudoexfoliation.
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PMID:Early diagnosis of glaucoma. II. The value of the initial examination in ocular hypertension. 357 6

RU 486 is a new water-insoluble drug which blocks peripheral glucocorticoid and progesterone receptors. As eye drops and by subconjunctival injection, it has been shown to lower normal rabbit intraocular pressure by a small amount. To try to improve the intraocular penetration, a water-soluble methochloride was prepared. In a series of 11 rabbits (initially 12: 1 died) treated in one eye at random with a 1% solution of the methochloride of RU 486 (vehicle drops to the fellow eye) no effect on intraocular pressure was found. The ionic nature of the methochloride may have prevented the drug becoming attached to, and blocking, the postulated glucocorticoid receptors in the rabbit outflow channels, although it may have penetrated the cornea more effectively.
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PMID:Water-soluble methochloride of RU 486 fails to reduce intraocular pressure in normal rabbits. 360 58

Previous work in our laboratory has shown that Cannabis sativa (marijuana) contains water-soluble, high molecular weight components that have extremely potent intraocular pressure (IOP) lowering activity. Aqueous extraction of other plants has now shown that a number of them also contain components with potent IOP lowering activity in rabbits. These include tobacco, cabbage, lettuce, several greens, Senecio anonymus, Erigeron philadelphicus, and several others. Not all plants tested were active, however, indicating that while more ubiquitous than originally thought, these materials are not apparently extractable from all plants. The chemical composition of the active fraction from tobacco was found to be different from that derived from Cannabis sativa.
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PMID:Water soluble high molecular weight components from plants with potent intraocular pressure lowering activity [corrected and republished ariticle originally printed in Curr Eye Res 1987 May;6(5):733-4]. 362 87

Protein kinase C was identified as a major protein kinase enzyme activity in rabbit ciliary processes. Phorbol myristate acetate (4 beta-PMA) in the presence of Ca2+ activated protein kinase C but did not directly affect the cyclic AMP-dependent protein kinase enzyme isolated from ciliary processes. To elucidate possible roles of protein kinase C, PMA was injected intravitreally into rabbit eyes. Fifty pmoles of PMA produced approximately a 40% decrease of the intraocular pressure relative to the control eye lasting for more than 72 hr. A reduction of intraocular pressure was still elicited by this dose of PMA in animals pretreated with systemic indomethacin given to suppress a possible inflammatory response. The biologically inactive analogue, 4 alpha-phorbol didecanoate (100 pmoles/eye) had no significant effect on intraocular pressure. In vivo and in vitro treatment with PMA had no significant effect on adenylate cyclase in ciliary process membranes assayed in vitro. However, protein kinase C isolated from rat brain, when added together with cofactors to membranes in vitro, augmented adenylate cyclase activation by isoproterenol, vasoactive intestinal peptide and aluminum fluoride. A slight increase in the basal activity and in the forskolin response was not statistically significant. The effect of protein kinase C to increase responsiveness of ciliary process adenylate cyclase was totally dependent on the presence of Ca2+ and was augmented by addition of PMA. These findings indicate modulation of adenylate cyclase activity by protein kinase C acting at the level of the G-proteins and suggest a possible role for this enzyme in water and electrolyte transport in the ciliary processes.
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PMID:Phorbol ester: effect on intraocular pressure, adenylate cyclase, and protein kinase in the rabbit eye. 367 53


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