PT  - JOURNAL ARTICLE
AU  - Sugrue, M F
AU  - Gautheron, P
AU  - Schmitt, C
AU  - Viader, M P
AU  - Conquet, P
AU  - Smith, R L
AU  - Share, N N
AU  - Stone, C A
TI  - On the pharmacology of L-645,151: a topically effective ocular hypotensive carbonic anhydrase inhibitor.
DP  - 1985 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 534--540
VI  - 232
IP  - 2
4099  - http://jpet.aspetjournals.org/content/232/2/534.short
4100  - http://jpet.aspetjournals.org/content/232/2/534.full
SO  - J Pharmacol Exp Ther1985 Feb 01; 232
AB  - L-645,151 [(2-sulfamoyl-6-benzothiazolyl)-2,2-dimethylpropionate] is the O-pivaloyl ester of L-643,799 (6-hydroxybenzothiazole-2-sulfonamide), topically administered L-645,151 being a substrate for ocular esterases with the resultant liberation of the active moiety, L-643,799, during penetration of the ocular surface. The minimum concentrations of topically administered suspensions (1 drop of 50 microliters into both eyes) of L-645,151, L-643,799, dichlorphenamide and methazolamide significantly lowering the elevated intraocular pressure (IOP) of the alpha-chymotrypsinized rabbit eye were 0.25, 2, 10 and 5%, respectively. IOP was not significantly decreased by 10% suspensions of acetazolamide or ethoxzolamide. The IOP lowering action of L-645,151 was local as the unilateral instillation of L-645,151 (0.25%) into the contralateral eye was devoid of effect in alpha-chymotrypsinized rabbits. L-645,151 (2%) decreased aqueous humor inflow in both the conscious rabbit and the anesthetized dog. Outflow facility in the conscious rabbit was unaltered by a 10% suspension of L-645,151. Low peak levels (0.52 microgram/g) of L-643,799 were present in rabbit renal cortex after the instillation of L-645,151 (2%) into both eyes; this treatment did not induce diuresis in the conscious rabbit. The corresponding maximum concentration in the iris + ciliary body was 4.01 micrograms/g. These preclinical studies reveal that L-645,151 is the most potent, topically effective ocular hypotensive carbonic anhydrase inhibitor described to date.