intraocular pressure

Aceclidine (1-azabicyclo[2.2.2]octan-3-yl acetate) is a modulator of M3 mAChR and can be used in studies about treating glaucoma by reducing intraocular pressure.

Methazolamide (CL 8490) is a carbonic anhydrase inhibitor that is used as a diuretic and in the treatment of glaucoma.

Bromfenac sodium hydrate (Bromfenac monosodium salt sesquihydrate) is the sodium salt form of bromfenac, a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and anti-inflammatory properties. Upon ophthalmic administration, bromfenac binds to and inhibits cyclooxygenase II (COX II), an enzyme that converts arachidonic acid to cyclic endoperoxides, which are prostaglandin (PG) precursors. By inhibiting PG formation, bromfenac prevents PG-induced inflammation, vasodilation, leukocytosis, disruption of the blood-aqueous humor barrier, increased vascular permeability, and elevated intraocular pressure (IOP).

DL-Adrenaline Hydrochloride is the hydrochloride salt of the naturally occurring sympathomimetic amine with vasoconstricting, intraocular pressure-reducing activities.

Brinzolamide (AL-4862) is a Carbonic Anhydrase Inhibitor. Its mechanism of action involves inhibiting the enzyme Carbonic Anhydrase.

Brimonidine Tartrate (AGN190342 tartrate) is a quinoxaline derivative and adrenergic α-2 receptor agonist (EC50: 0.45 nM) that is used to manage intraocular pressure associated with open-angle glaucoma or ocular hypertension.

(Rac)-MGV354 (MGV354) is the racemate of MGV354. MGV354 is a soluble activator of guanylate cyclase (sGC)(EC50s of <0.5 nM, and 5 nM in CHO and GTM-3 E cells, respectively).

Apraclonidine hydrochloride (ALO 2145) is an α2-adrenergic agonist and a weak α-1 adrenergic receptor agonist. Apraclonidine hydrochloride lowers intraocular pressure in human eyes and can be used in studies about glaucoma therapy.

Taprenepag (CP-544326) (CP-544326) is a potent and selective prostaglandin E2 receptor agonist (EC50 = 2.8 nM). Taprenepag has been used in trials studying the treatment of Ocular Hypertension and Glaucoma, Open-Angle.

Menabitan dihydrochloride (SP-204 dihydrochloride), the dihydrochloride salt of Menabitan, serves as a non-opioid analgesic agent by inhibiting phosphodiesterase 9 (PDE 9). Additionally, it has been shown to reduce intraocular pressure in a rabbit model .

Methazolamide-d6 is intended for use as an internal standard for the quantification of methazolamide by GC- or LC-MS. Methazolamide is a carbonic anhydrase inhibitor. It reduces intraocular pressure and cerebrospinal fluid flow in a rat model of glaucoma. Methazolamide reduces electroshock-induced seizures in rats with an ED50 value of 19.2 mg/kg. It also inhibits production of reactive oxygen species (ROS) in a primary cortical neuron (PCN) cellular model of subarachnoid hemorrhage (SAH) and reduces cerebral edema in a mouse model of SAH.3 Methazolamide is larvicidal, with a 50% larvicidal concentration (LC50) value of 724 ppm, but has no activity when administered in the diet to adult A. aegypti. Formulations containing methazolamide have been used in the treatment of glaucoma.

15-keto Prostaglandin F2α is a metabolite of Prostaglandin F2α that lowers intraocular pressure in rabbits.

GAT229 is a positive allosteric modulator of cannabinoid receptor 1 (CB1) and the S-(-) enantiomer of the CB1 modulator GAT211. It does not activate the receptor on its own but enhances the binding and activity of CB agonists. GAT229 (1 μM) enhances the binding of the CB1 full agonist CP 55,940 to CHO cells expressing human recombinant CB1 (hCB1), as well as the activity of 2-arachidonoyl glycerol , arachidonoyl ethanolamide , and CP 55,940 in arrestin2 recruitment assays and increases ERK1/2 and PLCβ3 phosphorylation in HEK293 cells expressing hCB1. GAT229 (1 μM) enhances depolarization-induced suppression of excitation but does not inhibit excitatory postsynaptic currents (EPSCs) in murine autaptic hippocampal neurons. GAT229 (0.2%, topical) reduces intraocular pressure by 5.8 and 7.7 mm Hg after 6 and 12 hours, respectively, in a transgenic mouse model of ocular hypertension using nose, ear, eye mutation (nee) mice.

Levobetaxolol, also known as AL-1577A and Betaxon, is a cardioselective β-adrenergic receptor inhibitor. It has been demonstrated to reduce intraocular pressure in patients affected by ocular hypertension and primary open-angle glaucoma.

Sovesudil (PHP-201) is a potent, ATP-competitive, locally acting Rho kinase (ROCK) inhibitor, showing IC50 values of 3.7 nM for ROCK-I and 2.3 nM for ROCK-II, and capable of lowering intraocular pressure (IOP) without inducing hyperemia.

AR-13503, is an metabolite of Netarsudil (AR-11324), is a Rho-associated protein kinase inhibitor. Netarsudil is potential useful for treating glaucoma and/or reducing intraocular pressure.

H-0104 Dihydrochloride is an inhibitor of ROCK that acts by applying potent intraocular pressure (IOP)-lowering effects into the eyes of monkeys.

Compound 7c, identified as carbonic anhydrase inhibitor 1, effectively inhibits carbonic anhydrase II. This inhibitor, also known as carbonic anhydrase inhibitor 3, lowers intraocular pressure in glaucomatous rabbits [1].

AR-13324 analog mesylate, an inhibitor of Rho-kinase and the norepinephrine transporter, reduces intraocular pressure in normotensive monkey eyes.

PGF2α isopropyl ester is an ester prodrug of PGF2α with enhanced lipid solubility. Due to better membrane penetration, PGF2α isopropyl ester is more suitable than PGF2α or PGF2α tromethamine salt for topical application in studies on intraocular pressure. The ester functionality is readily hydrolyzed in vivo to release the active compound PGF2α. When administered topically to the eyes of cynomolgus monkeys, a 5 μg dose reduces intraocular pressure by 68% after the fourth day of treatment.

GAT564 (Compound 15d) is a highly effective allosteric modulator of the cannabinoid 1 receptor (CB1R), with EC50 values of 87 nM for cAMP and 320 nM for β-arrestin2. It significantly enhances the binding of orthosteric ligands to hCB1R and exhibits remarkable efficacy as a topical agent, significantly reducing intraocular pressure (IOP) in an ocular normotensive murine model of glaucoma [1].

Bimatoprost is an F-series prostaglandin (PG) analog approved for use as an ocular hypotensive drug. Oxidation of the C-15 hydroxyl group and amide hydrolysis of Bimatoprost produces 15-keto-17-phenyl trinor PGF2α, a potential metabolite when administered to animals. 15-keto PG analogs can be minor impurities in commercial preparations of corresponding bulk drug compounds. Although much less potent than the parent compound, 15-keto PGs can still produce a small but measurable decrease (1 mm Hg) in intraocular pressure of normal cynomolgus monkeys at a dose of 1 μg eye. 15-keto Latanoprost (15-keto-17-phenyl-13,14-dihydro trinor PGF2α isopropyl ester) acts as a miotic in normal cat eyes, causing an 8 mm reduction in pupillary diameter at 5 μg eye. This is less potent compared to many other F-type PGs; for example, PGF2α induces similar miosis at less than 1 μg eye.

Bimatoprost grenod(15-(6-nitroxyhexanoyl)-17-phenyl trinor PGF2α) is a nitric oxide-donating derivative of 17-phenyl trinor PGF2α.1It increases cGMP levels in rabbit aqueous humor and iris ciliary body when topically administered at a concentration of 0.042%. Topical administration of 15-(6-nitroxylhexanoyl)-17-phenyl trinor PGF2α(0.14%) reduces intraocular hypertension (IOP) in a rabbit model of hypertonic saline-induced transient ocular pressure. It also reduces IOP in a cynomolgus monkey model of laser-induced ocular hypertension when administered topically at a concentration of 0.042%.

Netarsudil Dihydrochloride (AR-13324 Dihydrochloride) is an inhibitor of Rho-associated protein kinase (ROCK) and norepinephrine transporter (NET) with effective in intraocular pressure (IOP) reduction.

Latanoprost is an F-series prostaglandin (PG) analog which has been approved for use as an ocular hypotensive drug. Oxidation of the C-15 hydroxyl group without isopropyl ester hydrolysis produces 15-keto latanoprost. 15-keto Latanoprost is a potential metabolite of latanoprost when administered to animals. 15-keto Latanoprost is also one of the common minor impurities found in commercial preparations of the bulk drug compound. Although much less potent that the parent compound latanoprost, 15-keto latanoprost still retains the ability to produce a small but measurable decrease (1 mm Hg) in the intraocular pressure of normal cynomolgus monkeys when administered at a dose of 1 μg/eye. 15-keto Latanoprost is also a miotic in the normal cat eye, causing an 8 mm reduction in pupillary diameter at 5 μg/eye. Again, this is not as potent as many other F-type PGs; for example, PGF2α will produce this degree of miosis at a dose of less than 1 μg/eye. Products of β-oxidation account for most of the metabolites of latanoprost recovered in plasma and urine. However, 15-keto latanoprost is a minor metabolite, and one which could be enhanced in situations where β-oxidation is reduced.

Netarsudil, also known as AR-11324, is a Rho-associated protein kinase inhibitor. Netarsudil is potential useful for treating glaucoma and/or reducing intraocular pressure. Netarsudil Increases Outflow Facility in Human Eyes Through Multiple Mechanisms. Netarsudil inhibited kinases ROCK1 and ROCK2 with a Ki of 1 nM each, disrupted actin stress fibers and focal adhesions in TM cells with IC50s of 79 and 16 nM, respectively, and blocked the profibrotic effects of TGF-β2 in HTM cells. Netarsudil produced large reductions in IOP in rabbits and monkeys that were sustained for at least 24 h after once daily dosing, with transient, mild hyperemia observed as the only adverse effect.

Apraclonidine (ALO 2145) dihydrochloride is a selective α2 and weak α1 receptor agonist that effectively reduces intraocular pressure (IOP) in the eyes. It is available as a topical ophthalmic solution [1] [2].

Timolol hemimaleate ((S)-L-714,465; MK 950), a β-blocker, is formulated for both systemic and topical use. It is commonly applied topically to decrease intraocular pressure in cases of open-angle glaucoma and ocular hypertension. Additionally, it is utilized in research for the treatment of infantile hemangiomas, hypertension, myocardial infarction, migraine prophylaxis, and atrial fibrillation. Moreover, Timolol has been recognized for its cardioprotective effects [1] [2].

Verosudil (AR-12286) is a highly potent Rho kinase (ROCK) inhibitor with a Ki of 2 nM and 2 nM against ROCK1 and ROCK2, respectively. AR-12286 mitigates steroid-induced intraocular pressure in mice by decreasing intraocular pressure through enhanced outflow of aqueous humor via the trabecular meshwork.

Menabitan (SP-204) is a phosphodiesterase 9 (PDE 9) inhibitor used as a non-opioid analgesic. It has shown activity in reducing intraocular pressure in rabbit models.

Dichlorphenamide-13C6is intended for use as an internal standard for the quantification of dichlorphenamide by GC- or LC-MS. Dichlorphenamide is a sulfonamide and an orally bioavailable carbonic anhydrase (CA) inhibitor (Kis = 1.20, 38, 50, and 50 nM for the human CA isoforms CAI, CAII, CAIX, and CAXII, respectively).1It lowers intraocular pressure in rabbits when 50 μl of a 10% solution is applied topically to the eye.2Dichlorphenamide rescues the potassium deficiency and prevents insulin-induced paralysis in a rat model of familial hypokalemic periodic paralysis when administered at a dose of 5.6 mg/kg per day for ten days.3Formulations containing dichlorphenamide have been used in the treatment of glaucoma and primary periodic paralysis.

Prostaglandin F2α (PGF2α) activates the FP receptor, promoting smooth muscle contraction and luteolysis. 17-phenyl trinor PGF2α binds the FP receptor on ovine luteal cells with a relative potency of 756% compared to that of PGF2α. It is produced in vivo by the hydrolysis of 17-phenyl trinor PGF2α ethyl amide. 17-phenyl trinor PGF2α ethyl amide is used to reduce intraocular pressure related to glaucoma. 17-phenyl trinor PGF2α cyclopropyl methyl amide is a lipophilic analog of 17-phenyl trinor PGF2α. Amides of PGs may serve as prodrugs, as they are hydrolyzed in certain tissues to generate the bioactive free acid.

Bamosiran, a small interfering RNA (siRNA), specifically targets the β-adrenergic receptor 2 to reduce intraocular pressure.

Nipradolol (KT-210; K-351), an alpha-1-adrenergic receptor antagonist, effectively inhibits the elevation of intraocular pressure (IOP) induced by Phenylephrine in an albino rabbit model, suppresses noradrenaline (NA)-induced muscle contractions, and demonstrates vasodilatory effects on the coronary artery in dogs [1] [2].

Latanoprost is an F-series prostaglandin (PG) analog which has been approved for use as an ocular hypotensive drug. Latanoprost is an isopropyl ester, a prodrug form which is converted to latanoprost (free acid) by endogenous esterase enzymes. The free acid form is 200 times more potent than latanoprost as a ligand for the human recombinant FP receptor. 5-trans Latanoprost (free acid) is an isomer of latanoprost (free acid) wherein the double bond between carbons 5 and 6 has been changed from cis (Z) to trans (E). The trans isomer of latanoprost occurs as an impurity in commercial preparations of the bulk drug product. The present compound was prepared primarily as an analytical standard for detection and quantitation of this impurity. From what can be inferred from the study of other trans isomers of F-type prostaglandins, the biological activity of this isomer is likely to be similar to that of the cis isomer. However, there are no specific published reports on the biological activity, and on reducing intraocular pressure in particular, of 5-trans latanoprost.

AL 34662 is a selective and potent 5-HT2A receptor agonist with IC50s of 0.77 nM and 1.5 nM for rat and human 5-HT2 receptors, respectively.AL 34662 is also a low affinity α-1D adrenergic agonist, with an EC50 of 0.4 μM.AL 34662 can be used to lower intraocular pressure.

Prostaglandin F2α methyl ester is a highly lipid-soluble PGF2α analog used to maintain low intraocular pressure.

2MD, an orally active vitamin D analog, both stimulates periosteal bone formation and decreases trabecular bone resorption, effectively restoring trabecular and cortical bone mass and strength. Additionally, 2MD regulates genes related to intraocular pressure (IOP) and reduces IOP in non-human primates [1] [2].

15-keto Latanoprost is a potential metabolite of latanoprost when administered to animals and is a common minor impurity in commercial preparations of the bulk drug compound. Although much less potent than latanoprost, 15-keto Latanoprost can still produce a small but measurable decrease (1 mm Hg) in intraocular pressure in normal cynomolgus monkeys at a dose of 1 μg eye. It also acts as a miotic in normal cats, causing an 8 mm Hg reduction in pupillary diameter at 5 μg eye, though it is not as potent as many other F-type prostaglandins, such as prostaglandin F2α, which achieves the same effect at less than 1 μg eye.

Brinzolamide (AL-4862) hydrochloride is a selective inhibitor (IC50: 3.2 nM) of carbonic anhydrase II, inhibiting ciliary CA-II, reducing atrial fluid secretion, and thereby lowering intraocular pressure (IOP). It is useful for studying glaucoma disease.

H-0106 Dihydrochloride is an inhibitor of ROCK that acts by applying strong intraocular pressure (IOP)-lowering effects into the eyes of monkeys.

Biosynthesis of 12(R)-HETE in invertebrates is via lipoxygenation of arachidonic acid . In mammals, 12(R)-HETE can be produced by 12(R)-LOs and also by CYP450 oxidation. The activity of 12(R)-HETE in mammals is predominantly proinflammatory. 12(R)-HETE exhibits dose-dependent leukocyte chemotaxis at concentrations as low as 100 nM, and lowers intraocular pressure in rabbits.

Nabitan hydrochloride is a synthetic cannabinoid analog with antiemetic and analgesic effects. It may bind to and activate the CB1 and CB2 cannabinoid receptors. It also reduces intraocular pressure and may be useful in treating glaucoma.

Tafluprost ethyl amide, a prostaglandin derivative, reduces intraocular pressure (IOP) and affects eyelash growth, making it suitable for use in anti-glaucoma eye drops and cosmetics.

Latanoprost lactone diol is an important intermediate compound in the synthesis of Latanoprost. Latanoprost, classified as a prostaglandin F2α analogue, functions as an agonist for the FP prostanoid receptor, resulting in a reduction in intraocular pressure (IOP).

LX7101 is a potent inhibitor of both LIM kinase (LIMK) 1 and 2, and Rho-associated kinase 1 (ROCK1) and ROCK2, with IC50 values of 32, 4.3, 69, and 32 nM, respectively. It is selective, demonstrated by its lack of cross-reactivity in a panel of binding assays involving 78 receptors, transporters, and an additional 430 kinases, at a concentration of 10 μM. The topical administration of LX7101 (3 μl of a 1 mg/ml solution) to the eye has been shown to reduce intraocular pressure in a dexamethasone-induced mouse model of glaucoma.

Dichlorphenamide disodium is a specific, orally active carbonic anhydrase inhibitor. It effectively reduces intraocular pressure by impeding the secretion of aqueous humor. Notably, dichlorphenamide disodium holds potential for glaucoma research [1].

Carbonic anhydrase inhibitor 3 (compound 11g) is a carbonic anhydrase II inhibitor that reduces intraocular pressure in glaucomatous rabbits [1].

Adrenaline sulfate, an orally active hormone secreted by the adrenal glands' medulla, acts as an α-adrenergic and β-adrenergic receptor agonist. It is utilized in treating anaphylaxis and holds potential for cardiac arrest research.