The Experts below are selected from a list of 192 Experts worldwide ranked by ideXlab platform

Giovanna Mincione - One of the best experts on this subject based on the ideXlab platform.

  • carbonic anhydrase inhibitors part 70 synthesis and ocular pharmacology of a new class of water soluble topically effective intraocular pressure lowering agents derived from nicotinic acid and aromatic heterocyclic sulfonamides
    European Journal of Medicinal Chemistry, 1999
    Co-Authors: Claudiu T. Supuran, Andrea Scozzafava, Luca Menabuoni, Francesco Mincione, Fabrizio Briganti, Giovanna Mincione
    Abstract:

    Reaction of twenty aromatic/heterocyclic sulfonamides containing a free amino, imino, hydrazino or hydroxyl group, with nicotinoyl chloride afforded a series of water-soluble (as hydrochloride or triflate salts) compounds. The new derivatives were assayed as inhibitors of three carbonic anhydrase (CA) isozymes, hCA I, hCA II (cytosolic forms) and bCA IV (membrane-bound form); h = human, b = bovine isozyme. Efficient inhibition was observed against all three isozymes, but especially against hCA II and bCA IV (in nanomolar range), two isozymes known to play a critical role in aqueous humour secretion within the ciliary processes of the eye. Some of the best inhibitors synthesized were applied as 2% water solutions directly into the eye of normotensive or glaucomatous albino rabbits. Very strong intraocular pressure (IOP) lowering was observed for many of them, and the active Drug was detected in eye tissues and fluids. This result prompted us to re-analyse the synthetic work done by other groups for the design of water soluble, topically effective Antiglaucoma sulfonamides. According to these researchers, the IOP lowering effect is due to the intrinsic nature of the specific heterocyclic sulfonamide considered, among which the thienothiopyran-2-sulfonamide derivatives represent the best studied case. Indeed, the first agents developed for such applications, such as dorzolamide, are derivatives of this ring system. In order to prove that the tail (in this case the nicotinoyl moiety) conferring water solubility to a sulfonamide CA inhibitor is critically important, similarly to the ring to which the sulfonamido group is grafted, we also prepared a dorzolamide derivative to which the nicotinoyl moiety was attached. This new compound is more water soluble than dorzolamide (as hydrochloride salt), behaves as a strong CA II inhibitor, and acts similarly to the parent derivative in lowering IOP in experimental animals. Thus, it seems that the tail conferring water solubility is more important for topical activity as an Antiglaucoma Drug than the heterocyclic/aromatic ring to which the sulfonamido moiety is grafted.

  • carbonic anhydrase inhibitors part 71 synthesis and ocular pharmacology of a new class of water soluble topically effective intraocular pressure lowering sulfonamides incorporating picolinoyl moieties
    European Journal of Pharmaceutical Sciences, 1999
    Co-Authors: Claudiu T. Supuran, Andrea Scozzafava, Luca Menabuoni, Francesco Mincione, Fabrizio Briganti, Giovanna Mincione
    Abstract:

    Reaction of 20 aromatic/heterocyclic sulfonamides containing a free amino, imino, hydrazino or hydroxyl group, with picolinic acid in the presence of carbodiimide derivatives afforded a series of water-soluble (as hydrochloride or triflate salts) compounds. The new derivatives were assayed as inhibitors of three carbonic anhydrase (CA) isozymes, CA I, II (cytosolic forms) and IV (membrane-bound form). Efficient inhibition was observed against all three isozymes, but especially against CA II and CA IV (in nanomolar range), the two isozymes known to play a critical role in aqueous humor secretion within the ciliary processes of the eye. Some of the best inhibitors synthesized were applied as 2% water solutions directly into the eye of normotensive or glaucomatous albino rabbits. Very strong intraocular pressure (IOP) lowering was observed for many of them, and the active Drug was detected in eye tissues and fluids. This result prompted us to reanalyze the synthetic work done by other groups for the design of water soluble, topically effective Antiglaucoma sulfonamides. According to these researchers, the IOP lowering effect is due to the intrinsic nature of the specific heterocyclic sulfonamide considered, among which the thienothiopyran-2-sulfonamide derivatives represent the best studied case. Indeed, the first agents developed for such applications, such as dorzolamide, are derivatives of this ring system. In order to prove that the tail (in this case the picolinoyl moiety) conferring water solubility to a sulfonamide CA inhibitor is critically important for its topical effectiveness, similarly to the ring to which the sulfonamido group is grafted, we also prepared a dorzolamide derivative to which the picolinoyl moiety was attached. This new compound is more water soluble than dorzolamide (as hydrochloride salt), behaves as a strong CA II inhibitor, and acts similarly to the parent derivative in lowering IOP in experimental animals. Thus, it seems that the tail conferring water solubility is more important for topical activity as Antiglaucoma Drug, than the heterocyclic/aromatic ring to which the sulfonamido moiety is grafted.

Li-jyuan Luo - One of the best experts on this subject based on the ideXlab platform.

  • The role of alkyl chain length of monothiol-terminated alkyl carboxylic acid in the synthesis, characterization, and application of gelatin-g-poly(N-isopropylacrylamide) carriers for Antiglaucoma Drug delivery
    Acta biomaterialia, 2016
    Co-Authors: Li-jyuan Luo, Jui-yang Lai
    Abstract:

    Abstract To improve ocular bioavailability and extend pharmacological response, this study aims to investigate the role of alkyl chain length of monothiol-terminated alkyl carboxylic acids in the synthesis, characterization, and application of gelatin-g-poly(N-isopropylacrylamide) (GN) biodegradable in situ gelling carriers for Antiglaucoma Drug delivery. In the presence of mercaptoacetic acid (MAA), mercaptopropionic acid (MPA), mercaptobutyric acid (MBA), or mercaptohexanoic acid (MHA) as a chain transfer agent, the carboxylic end-capped poly(N-isopropylacrylamide) samples were prepared by free radical polymerization technique. Our results showed that with increasing alkyl chain length, the hydrophobicity of thermo-responsive polymer segments significantly increased, mainly due to an increase in C H stretching frequencies. In addition, the greater hydrophobic association favored the decrease in both phase transition temperature and weight loss of GN copolymers, thereby accelerating their temperature-triggered gelation process and retarding the degradation progress under physiological conditions. The benefits from these features allowed the pilocarpine carriers to increase Drug payload and extend Drug release. Irrespective of carbon number of monothiol-terminated alkyl carboxylic acid, the synthesized GN materials exhibited high tolerance to corneal endothelial cells without any evidence of inhibited proliferation, viability loss, inflammatory stimulation, and functional abnormality, indicating good biocompatibility. Results of clinical observations and histological examinations demonstrated that the therapeutic efficacies in treating glaucomatous damage are in response to in vivo Drug release profiles from various intracamerally injected GN carriers. The research findings suggest the influence of alkyl chain length of chain transfer agent-mediated polymer hydrophobicity and degradability on pharmacological bioavailability and action of pilocarpine in a glaucomatous rabbit model. Statement of Significance Considering that glaucoma is a chronic disease that requires long-term medical therapy to preserve vision in patients, it is highly desirable to augment pharmacological bioavailability and govern release profile by tuning the properties of Drug delivery carriers. For the first time, the present study provide striking evidence that the alkyl chain length of monothiol-terminated alkyl carboxylic acid related to the synthesis of biodegradable in situ gelling copolymers plays a key role in molecular functionalization of intracameral delivery systems for ocular administration and controlled release of Antiglaucoma medications. The therapeutic efficacies in treating glaucomatous damage are in response to in vivo pilocarpine release profiles modulated by the carbon number of thermo-responsive polymer segment-mediated carrier hydrophobicity and degradability.

  • Antioxidant Gallic Acid-Functionalized Biodegradable in Situ Gelling Copolymers for Cytoprotective Antiglaucoma Drug Delivery Systems.
    Biomacromolecules, 2015
    Co-Authors: Jui-yang Lai, Li-jyuan Luo
    Abstract:

    In clinical ophthalmology, oxidative stress has been proposed as the initiating cause of ocular hypertension, which is one of the risk factors for glaucomatous damage and disease progression. In an attempt to improve the therapeutic efficacy of intracamerally administered pilocarpine, herein, a cytoprotective Antiglaucoma Drug delivery system composed of antioxidant gallic acid (GA)-functionalized gelatin-g-poly(N-isopropylacrylamide) (GN) biodegradable in situ gelling copolymer was developed for the first time. Analyses by UV-vis and Fourier transform infrared spectroscopies showed the formation of biopolymer-antioxidant covalent linkages in GNGA structures through a radical reaction in the presence of water-soluble redox initiators. The synthesized GNGA polymers with strong free radical scavenging effectiveness exhibited appropriate phase transition temperature and degradation rate as injectable bioerodible depots for minimally invasive pilocarpine delivery to the ocular anterior chamber. During the 2-week in vitro study, the sustained releases of sufficient amounts of pilocarpine for a therapeutic action in alleviating ocular hypertension could be achieved under physiological conditions. Results of cell viability, intracellular reactive oxygen species level, and intracellular calcium concentration indicated that the incorporation of antioxidant GA into GN structure can enhance cytoprotective effects of carrier materials against hydrogen peroxide-induced oxidative stress in lens epithelial cultures. Effective pharmacological responses (i.e., reduction of intraocular pressure and preservation of corneal endothelial cell morphology and density) in rabbits receiving intracameral GNGA injections containing pilocarpine were evidenced by clinical observations. The findings of in vivo studies also support the hypothesis that the GNGA carriers are more advantageous over their GN counterparts for the improvement of total antioxidant status in glaucomatous eyes with chronic ocular hypertension. The synthesized multifunctional molecules may be further used as potential polymer therapeutics for intraocular delivery of bioactive agents.

  • Antioxidant Gallic Acid-Functionalized Biodegradable in Situ Gelling Copolymers for Cytoprotective Antiglaucoma Drug Delivery Systems
    2015
    Co-Authors: Jui-yang Lai, Li-jyuan Luo
    Abstract:

    In clinical ophthalmology, oxidative stress has been proposed as the initiating cause of ocular hypertension, which is one of the risk factors for glaucomatous damage and disease progression. In an attempt to improve the therapeutic efficacy of intracamerally administered pilocarpine, herein, a cytoprotective Antiglaucoma Drug delivery system composed of antioxidant gallic acid (GA)-functionalized gelatin-g-poly­(N-isopropylacrylamide) (GN) biodegradable in situ gelling copolymer was developed for the first time. Analyses by UV–vis and Fourier transform infrared spectroscopies showed the formation of biopolymer–antioxidant covalent linkages in GNGA structures through a radical reaction in the presence of water-soluble redox initiators. The synthesized GNGA polymers with strong free radical scavenging effectiveness exhibited appropriate phase transition temperature and degradation rate as injectable bioerodible depots for minimally invasive pilocarpine delivery to the ocular anterior chamber. During the 2-week in vitro study, the sustained releases of sufficient amounts of pilocarpine for a therapeutic action in alleviating ocular hypertension could be achieved under physiological conditions. Results of cell viability, intracellular reactive oxygen species level, and intracellular calcium concentration indicated that the incorporation of antioxidant GA into GN structure can enhance cytoprotective effects of carrier materials against hydrogen peroxide-induced oxidative stress in lens epithelial cultures. Effective pharmacological responses (i.e., reduction of intraocular pressure and preservation of corneal endothelial cell morphology and density) in rabbits receiving intracameral GNGA injections containing pilocarpine were evidenced by clinical observations. The findings of in vivo studies also support the hypothesis that the GNGA carriers are more advantageous over their GN counterparts for the improvement of total antioxidant status in glaucomatous eyes with chronic ocular hypertension. The synthesized multifunctional molecules may be further used as potential polymer therapeutics for intraocular delivery of bioactive agents

Jui-yang Lai - One of the best experts on this subject based on the ideXlab platform.

  • The role of alkyl chain length of monothiol-terminated alkyl carboxylic acid in the synthesis, characterization, and application of gelatin-g-poly(N-isopropylacrylamide) carriers for Antiglaucoma Drug delivery
    Acta biomaterialia, 2016
    Co-Authors: Li-jyuan Luo, Jui-yang Lai
    Abstract:

    Abstract To improve ocular bioavailability and extend pharmacological response, this study aims to investigate the role of alkyl chain length of monothiol-terminated alkyl carboxylic acids in the synthesis, characterization, and application of gelatin-g-poly(N-isopropylacrylamide) (GN) biodegradable in situ gelling carriers for Antiglaucoma Drug delivery. In the presence of mercaptoacetic acid (MAA), mercaptopropionic acid (MPA), mercaptobutyric acid (MBA), or mercaptohexanoic acid (MHA) as a chain transfer agent, the carboxylic end-capped poly(N-isopropylacrylamide) samples were prepared by free radical polymerization technique. Our results showed that with increasing alkyl chain length, the hydrophobicity of thermo-responsive polymer segments significantly increased, mainly due to an increase in C H stretching frequencies. In addition, the greater hydrophobic association favored the decrease in both phase transition temperature and weight loss of GN copolymers, thereby accelerating their temperature-triggered gelation process and retarding the degradation progress under physiological conditions. The benefits from these features allowed the pilocarpine carriers to increase Drug payload and extend Drug release. Irrespective of carbon number of monothiol-terminated alkyl carboxylic acid, the synthesized GN materials exhibited high tolerance to corneal endothelial cells without any evidence of inhibited proliferation, viability loss, inflammatory stimulation, and functional abnormality, indicating good biocompatibility. Results of clinical observations and histological examinations demonstrated that the therapeutic efficacies in treating glaucomatous damage are in response to in vivo Drug release profiles from various intracamerally injected GN carriers. The research findings suggest the influence of alkyl chain length of chain transfer agent-mediated polymer hydrophobicity and degradability on pharmacological bioavailability and action of pilocarpine in a glaucomatous rabbit model. Statement of Significance Considering that glaucoma is a chronic disease that requires long-term medical therapy to preserve vision in patients, it is highly desirable to augment pharmacological bioavailability and govern release profile by tuning the properties of Drug delivery carriers. For the first time, the present study provide striking evidence that the alkyl chain length of monothiol-terminated alkyl carboxylic acid related to the synthesis of biodegradable in situ gelling copolymers plays a key role in molecular functionalization of intracameral delivery systems for ocular administration and controlled release of Antiglaucoma medications. The therapeutic efficacies in treating glaucomatous damage are in response to in vivo pilocarpine release profiles modulated by the carbon number of thermo-responsive polymer segment-mediated carrier hydrophobicity and degradability.

  • Antioxidant Gallic Acid-Functionalized Biodegradable in Situ Gelling Copolymers for Cytoprotective Antiglaucoma Drug Delivery Systems.
    Biomacromolecules, 2015
    Co-Authors: Jui-yang Lai, Li-jyuan Luo
    Abstract:

    In clinical ophthalmology, oxidative stress has been proposed as the initiating cause of ocular hypertension, which is one of the risk factors for glaucomatous damage and disease progression. In an attempt to improve the therapeutic efficacy of intracamerally administered pilocarpine, herein, a cytoprotective Antiglaucoma Drug delivery system composed of antioxidant gallic acid (GA)-functionalized gelatin-g-poly(N-isopropylacrylamide) (GN) biodegradable in situ gelling copolymer was developed for the first time. Analyses by UV-vis and Fourier transform infrared spectroscopies showed the formation of biopolymer-antioxidant covalent linkages in GNGA structures through a radical reaction in the presence of water-soluble redox initiators. The synthesized GNGA polymers with strong free radical scavenging effectiveness exhibited appropriate phase transition temperature and degradation rate as injectable bioerodible depots for minimally invasive pilocarpine delivery to the ocular anterior chamber. During the 2-week in vitro study, the sustained releases of sufficient amounts of pilocarpine for a therapeutic action in alleviating ocular hypertension could be achieved under physiological conditions. Results of cell viability, intracellular reactive oxygen species level, and intracellular calcium concentration indicated that the incorporation of antioxidant GA into GN structure can enhance cytoprotective effects of carrier materials against hydrogen peroxide-induced oxidative stress in lens epithelial cultures. Effective pharmacological responses (i.e., reduction of intraocular pressure and preservation of corneal endothelial cell morphology and density) in rabbits receiving intracameral GNGA injections containing pilocarpine were evidenced by clinical observations. The findings of in vivo studies also support the hypothesis that the GNGA carriers are more advantageous over their GN counterparts for the improvement of total antioxidant status in glaucomatous eyes with chronic ocular hypertension. The synthesized multifunctional molecules may be further used as potential polymer therapeutics for intraocular delivery of bioactive agents.

  • Antioxidant Gallic Acid-Functionalized Biodegradable in Situ Gelling Copolymers for Cytoprotective Antiglaucoma Drug Delivery Systems
    2015
    Co-Authors: Jui-yang Lai, Li-jyuan Luo
    Abstract:

    In clinical ophthalmology, oxidative stress has been proposed as the initiating cause of ocular hypertension, which is one of the risk factors for glaucomatous damage and disease progression. In an attempt to improve the therapeutic efficacy of intracamerally administered pilocarpine, herein, a cytoprotective Antiglaucoma Drug delivery system composed of antioxidant gallic acid (GA)-functionalized gelatin-g-poly­(N-isopropylacrylamide) (GN) biodegradable in situ gelling copolymer was developed for the first time. Analyses by UV–vis and Fourier transform infrared spectroscopies showed the formation of biopolymer–antioxidant covalent linkages in GNGA structures through a radical reaction in the presence of water-soluble redox initiators. The synthesized GNGA polymers with strong free radical scavenging effectiveness exhibited appropriate phase transition temperature and degradation rate as injectable bioerodible depots for minimally invasive pilocarpine delivery to the ocular anterior chamber. During the 2-week in vitro study, the sustained releases of sufficient amounts of pilocarpine for a therapeutic action in alleviating ocular hypertension could be achieved under physiological conditions. Results of cell viability, intracellular reactive oxygen species level, and intracellular calcium concentration indicated that the incorporation of antioxidant GA into GN structure can enhance cytoprotective effects of carrier materials against hydrogen peroxide-induced oxidative stress in lens epithelial cultures. Effective pharmacological responses (i.e., reduction of intraocular pressure and preservation of corneal endothelial cell morphology and density) in rabbits receiving intracameral GNGA injections containing pilocarpine were evidenced by clinical observations. The findings of in vivo studies also support the hypothesis that the GNGA carriers are more advantageous over their GN counterparts for the improvement of total antioxidant status in glaucomatous eyes with chronic ocular hypertension. The synthesized multifunctional molecules may be further used as potential polymer therapeutics for intraocular delivery of bioactive agents

Claudiu T. Supuran - One of the best experts on this subject based on the ideXlab platform.

  • Discovery of curcumin inspired sulfonamide derivatives as a new class of carbonic anhydrase isoforms I, II, IX, and XII inhibitors
    Taylor & Francis Group, 2017
    Co-Authors: P. Sri V. Ramya, Srinivas Angapelly, Andrea Angeli, Chander Singh Digwal, Mohammed Arifuddin, Bathini Nagendra Babu, Claudiu T. Supuran, Ahmed Kamal
    Abstract:

    A series of curcumin inspired sulfonamide derivatives was prepared from various chalcones and 4-sulfamoyl benzaldehyde via Claisen–Schmidt condensation. All new compounds were assayed as inhibitors of four human isoforms of the metalloenzyme carbonic anhydrase (hCA, EC 4.2.1.1) isoforms hCA I, II, IX and XII. Interesting inhibitory activities were observed against all these isoforms. hCA I, an isoform involved in several eye diseases was inhibited moderately with KIs in the range of 191.8–904.2 nM, hCA II, an Antiglaucoma Drug target was highly inhibited by the new sulfonamides, with KIs in the range of 0.75–8.8 nM. hCA IX, a tumor-associated isoform involved in cancer progression and metastatic spread was potently inhibited by the new sulfonamides, with KIs in the range of 2.3–87.3 nM, whereas hCA XII, and Antiglaucoma and anticancer Drug target, was inhibited with KIs in the range of 6.1–71.8 nM. It is noteworthy that one of the new compounds, 5d, was found to be almost 9 times more selective against hCA II (KI = 0.89 nM) over hCA IX and hCA XII, whereas 5e was 3 and 70 times more selective against hCA II (KI = 0.75 nM) over hCA IX and hCA XII, respectively

  • carbonic anhydrase inhibitors part 70 synthesis and ocular pharmacology of a new class of water soluble topically effective intraocular pressure lowering agents derived from nicotinic acid and aromatic heterocyclic sulfonamides
    European Journal of Medicinal Chemistry, 1999
    Co-Authors: Claudiu T. Supuran, Andrea Scozzafava, Luca Menabuoni, Francesco Mincione, Fabrizio Briganti, Giovanna Mincione
    Abstract:

    Reaction of twenty aromatic/heterocyclic sulfonamides containing a free amino, imino, hydrazino or hydroxyl group, with nicotinoyl chloride afforded a series of water-soluble (as hydrochloride or triflate salts) compounds. The new derivatives were assayed as inhibitors of three carbonic anhydrase (CA) isozymes, hCA I, hCA II (cytosolic forms) and bCA IV (membrane-bound form); h = human, b = bovine isozyme. Efficient inhibition was observed against all three isozymes, but especially against hCA II and bCA IV (in nanomolar range), two isozymes known to play a critical role in aqueous humour secretion within the ciliary processes of the eye. Some of the best inhibitors synthesized were applied as 2% water solutions directly into the eye of normotensive or glaucomatous albino rabbits. Very strong intraocular pressure (IOP) lowering was observed for many of them, and the active Drug was detected in eye tissues and fluids. This result prompted us to re-analyse the synthetic work done by other groups for the design of water soluble, topically effective Antiglaucoma sulfonamides. According to these researchers, the IOP lowering effect is due to the intrinsic nature of the specific heterocyclic sulfonamide considered, among which the thienothiopyran-2-sulfonamide derivatives represent the best studied case. Indeed, the first agents developed for such applications, such as dorzolamide, are derivatives of this ring system. In order to prove that the tail (in this case the nicotinoyl moiety) conferring water solubility to a sulfonamide CA inhibitor is critically important, similarly to the ring to which the sulfonamido group is grafted, we also prepared a dorzolamide derivative to which the nicotinoyl moiety was attached. This new compound is more water soluble than dorzolamide (as hydrochloride salt), behaves as a strong CA II inhibitor, and acts similarly to the parent derivative in lowering IOP in experimental animals. Thus, it seems that the tail conferring water solubility is more important for topical activity as an Antiglaucoma Drug than the heterocyclic/aromatic ring to which the sulfonamido moiety is grafted.

  • carbonic anhydrase inhibitors part 71 synthesis and ocular pharmacology of a new class of water soluble topically effective intraocular pressure lowering sulfonamides incorporating picolinoyl moieties
    European Journal of Pharmaceutical Sciences, 1999
    Co-Authors: Claudiu T. Supuran, Andrea Scozzafava, Luca Menabuoni, Francesco Mincione, Fabrizio Briganti, Giovanna Mincione
    Abstract:

    Reaction of 20 aromatic/heterocyclic sulfonamides containing a free amino, imino, hydrazino or hydroxyl group, with picolinic acid in the presence of carbodiimide derivatives afforded a series of water-soluble (as hydrochloride or triflate salts) compounds. The new derivatives were assayed as inhibitors of three carbonic anhydrase (CA) isozymes, CA I, II (cytosolic forms) and IV (membrane-bound form). Efficient inhibition was observed against all three isozymes, but especially against CA II and CA IV (in nanomolar range), the two isozymes known to play a critical role in aqueous humor secretion within the ciliary processes of the eye. Some of the best inhibitors synthesized were applied as 2% water solutions directly into the eye of normotensive or glaucomatous albino rabbits. Very strong intraocular pressure (IOP) lowering was observed for many of them, and the active Drug was detected in eye tissues and fluids. This result prompted us to reanalyze the synthetic work done by other groups for the design of water soluble, topically effective Antiglaucoma sulfonamides. According to these researchers, the IOP lowering effect is due to the intrinsic nature of the specific heterocyclic sulfonamide considered, among which the thienothiopyran-2-sulfonamide derivatives represent the best studied case. Indeed, the first agents developed for such applications, such as dorzolamide, are derivatives of this ring system. In order to prove that the tail (in this case the picolinoyl moiety) conferring water solubility to a sulfonamide CA inhibitor is critically important for its topical effectiveness, similarly to the ring to which the sulfonamido group is grafted, we also prepared a dorzolamide derivative to which the picolinoyl moiety was attached. This new compound is more water soluble than dorzolamide (as hydrochloride salt), behaves as a strong CA II inhibitor, and acts similarly to the parent derivative in lowering IOP in experimental animals. Thus, it seems that the tail conferring water solubility is more important for topical activity as Antiglaucoma Drug, than the heterocyclic/aromatic ring to which the sulfonamido moiety is grafted.

Kanjiro Masuda - One of the best experts on this subject based on the ideXlab platform.

  • Effects of topical nipradilol, a β blocking agent with α blocking and nitroglycerin-like activities, on intraocular pressure and aqueous dynamics in humans
    The British journal of ophthalmology, 2000
    Co-Authors: Mikiko Kanno, Makoto Araie, Hiroshi Koibuchi, Kanjiro Masuda
    Abstract:

    AIMS—To study the effects of topical nipradilol, a non-selective β blocker with α blocking and nitroglycerin-like activities, on intraocular pressure (IOP) and aqueous humour dynamics in normal humans and in patients with ocular hypertension. METHODS—Nipradilol (0.06%, 0.125%, 0.25%, 0.5%) was applied to normal volunteers (n = 12) to test for IOP lowering effects. In a second group of normal volunteers (n = 11), nipradilol (0.125% and 0.25%) and timolol (0.5%) were compared for IOP lowering effects. After a single administration of 0.25% nipradilol, IOP, flare intensity in the anterior chamber, aqueous flow, uveoscleral outflow, tonographic outflow facility, and episcleral venous pressure were either directly measured or mathematically calculated. Topical nipradilol (0.25%) was administered to 24 patients with ocular hypertension twice daily for 8 weeks. RESULTS—Administration of 0.25% nipradilol decreased IOP with a maximum reduction of 4.2 mm Hg lasting 12 hours. A single instillation of both 0.25% nipradilol and 0.5% timolol reduced the IOP in normotensive human subjects to the same degree. A single instillation of 0.25% nipradilol decreased the aqueous flow rate in the treated eye by 20%. Nipradilol produced no significant effect in tonographic outflow facility or episcleral venous pressure, but uveoscleral outflow was increased. In patients with ocular hypertension, twice daily instillation of 0.25% nipradilol decreased IOP without tachyphylaxis for the 8 week test period. CONCLUSION—Topical nipradilol (0.25%) reduced IOP by decreasing the aqueous flow rate and probably also by increasing uveoscleral outflow. Nipradilol should be further investigated as a new Antiglaucoma Drug.

  • effects of topical nipradilol a beta blocking agent with alpha blocking and nitroglycerin like activities on intraocular pressure and aqueous dynamics in humans
    British Journal of Ophthalmology, 2000
    Co-Authors: Mikiko Kanno, Makoto Araie, Hiroshi Koibuchi, Kanjiro Masuda
    Abstract:

    AIMS—To study the effects of topical nipradilol, a non-selective β blocker with α blocking and nitroglycerin-like activities, on intraocular pressure (IOP) and aqueous humour dynamics in normal humans and in patients with ocular hypertension. METHODS—Nipradilol (0.06%, 0.125%, 0.25%, 0.5%) was applied to normal volunteers (n = 12) to test for IOP lowering effects. In a second group of normal volunteers (n = 11), nipradilol (0.125% and 0.25%) and timolol (0.5%) were compared for IOP lowering effects. After a single administration of 0.25% nipradilol, IOP, flare intensity in the anterior chamber, aqueous flow, uveoscleral outflow, tonographic outflow facility, and episcleral venous pressure were either directly measured or mathematically calculated. Topical nipradilol (0.25%) was administered to 24 patients with ocular hypertension twice daily for 8 weeks. RESULTS—Administration of 0.25% nipradilol decreased IOP with a maximum reduction of 4.2 mm Hg lasting 12 hours. A single instillation of both 0.25% nipradilol and 0.5% timolol reduced the IOP in normotensive human subjects to the same degree. A single instillation of 0.25% nipradilol decreased the aqueous flow rate in the treated eye by 20%. Nipradilol produced no significant effect in tonographic outflow facility or episcleral venous pressure, but uveoscleral outflow was increased. In patients with ocular hypertension, twice daily instillation of 0.25% nipradilol decreased IOP without tachyphylaxis for the 8 week test period. CONCLUSION—Topical nipradilol (0.25%) reduced IOP by decreasing the aqueous flow rate and probably also by increasing uveoscleral outflow. Nipradilol should be further investigated as a new Antiglaucoma Drug.