Levobunolol 0.5% eye drops 0.4ml unit dose preservative free

ABSTRACT There is increasing evidence, from cellular, animal and human epidemiological studies, linking β‐blockers with reductions in cancer growth and metastasis. Propranolol is the most investigated β‐blocker for cancer; although as many different off‐patent β‐blockers exist, there is little commercial incentive to drive comparative clinical trials. To minimize any chance of endogenous β‐agonist driven cancer growth or metastasis, theoretically, the “ideal” anti‐cancer β‐blocker would have high affinity, no partial agonism, and long duration of action at β2‐adrenoceptors (and for some cancers, additionally at β1 or β3‐AR). Using CHO cells stably expressing the wildtype and polymorphic variants of the human β1 and β1‐adrenoceptors, this study assessed 35 β‐blockers for the affinity and duration of binding (using 3 H‐CGP12177 whole cell binding) and intrinsic efficacy (CRE‐gene transcription). Despite high affinity, some β‐blockers had a short binding duration (e.g., alprenolol, bupranolol, levobunolol, nadolol and oxprenolol). Other compounds had substantial partial agonism (e.g., cyanopindolol, bucindolol, pindolol, pronethalol and xamoterol) and other compounds had a biphasic washout (e.g., bucindolol, timolol, carpindolol, and CGP12177) for reasons unknown. Considering all 3 factors, carazolol and ICI118551 may be more “ideal” than propranolol; however, carvedilol, with higher affinity and substantially longer duration of β2 (and β1) receptor binding than propranolol whilst maintaining low partial agonism, may be the most theoretically optimal. Furthermore, it is already widely used in cardiovascular medicine as an off‐patent tablet. Thus, carvedilol may have more optimal molecular pharmacological characteristics for an “anti‐cancer” β‐blocker than propranolol and could enter prospective comparative clinical trials without needing any further clinical workup.

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Glaucoma is a disease associated with increased intraocular pressure (IOP). Of the pharmacological agents for treating glaucoma, there are drugs of the first (most effective and safe) and second-line treatment. First-line treatment includes prostaglandin analogs and beta-blockers. The currently used prostaglandin analogs (latanoprost, bimatoprost, tafluprost and travoprost) are PG F2α analogs that act through stimulation of FP receptors. They are distinguished by the optimal ratio of effectiveness and risk of side effects. They are convenient for the patient because for the therapeutic effect, it is enough to prescribe 1 time per day. As a result, it is rational to start the treatment of glaucoma with a drug in this group. In terms of pharmacoeconomics, the most affordable prostaglandin drug is latanoprost, which is generally as effective as other prostaglandin analogs. β-adrenergic blockers reduce the production of intraocular fluid, the formation of which is controlled by β1- and β2-adrenergic receptors. Therefore, non-selective β-blockers (timolol, levobunolol, metipranolol, and carteolol) have a pharmacodynamic advantage over selective β1-adrenergic antagonists (betaxolol). Conducted clinical studies of β-blockers have shown that given the cost, efficacy and safety, timolol was the most preferable treatment for glaucoma. In the presence of medical contraindications to the use of first-line drugs or to enhance their effectiveness, α2-agonists (apraclonidine and brimonidine), carbonic anhydrase inhibitors (usually local action: dorzolamide and brinzolamide), M-cholinomimetics (pilocarpine, carbachol and echothiopate), and also Rho-kinase inhibitors (ripasudil)

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