R-enantiomer of timolol: a potential selective ocular antihypertensive agent.
Various studies were conducted to evaluate the effects of timolol, an S-enantiomer, relative to its R-enantiomer upon intraocular pressure and related ocular systems in the rabbit. The R-enantiomer was about one-third as potent as timolol in displacing 3H-dihydroalprenolol binding to iris-ciliary body tissue, reducing aqueous humor formation, and lowering intraocular pressure of alpha-chymotrypsin hypertensive eyes. In contrast, the R-enantiomer was 50 to 90 times less potent than timolol in antagonizing the effects of isoproterenol on pulmonary and atrial beta-adrenergic receptors. The data indicate that the R-enantiomer may lower intraocular pressure in man at concentrations less likely than timolol to block extraocular beta-adrenergic receptors. Finally, to account for the differential effect of the R-enantiomer upon ocular as opposed to extraocular beta-adrenergic receptors, it is tentatively suggested that this agent may also act upon a population of ocular beta-adrenergic receptors showing relatively poor stereoselectively.
D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects / Q000378:metabolism; D001665:Binding Sites / Q000187:drug effects; D001980:Bronchi / Q000378:metabolism; D002918:Chymotrypsin / Q000009:adverse effects; D002924:Ciliary Body / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005901:Glaucoma / Q000188:drug therapy*; D006168:Guinea Pigs; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D007498:Iris / Q000378:metabolism; D008297:Male; D009798:Ocular Hypertension / Q000139:chemically induced; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D013997:Time Factors; D013999:Timolol / Q000494:pharmacology* / Q000627:therapeutic use; D014132:Trachea / Q000378:metabolism
D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D013999:Timolol; D002918:Chymotrypsin