Dorzolamide-d5 (hydrochloride) (Synonyms: L-671,152-d5, MK-507-d5)

Dorzolamide-d₅ is intended for use as an internal standard for the quantification of dorzolamide by GC- or LC-MS. Dorzolamide is an inhibitor of carbonic anhydrase (CA), inhibiting CAII, CAV, CAVI, CAIX, CAXII, CAXIII, and CAXIV with K_i values ranging from 3.5 to 52 nM.^1,2,3 It is selective for these isoforms over CAI, CAIII, and CAIV (K_is = 50, 8, and 8.5 μM, respectively).¹ Dorzolamide inhibits carbonic anhydrase in isolated rabbit iris-ciliary body by 87% when used at a concentration of 0.02%.³ It also reduces intraocular pressure in an α-chymotrypsin-treated rabbit model of ocular hypertension and in normotensive rabbits when applied topically at a concentration of 0.5%.³ Formulations containing dorzolamide have been used in the treatment of glaucoma.^4,5

1.Supuran, C.T., and Scozzafava, A.Carbonic anhydrases as targets for medicinal chemistryBioorganic & Medicinal Chemistry15(13)4336-4350(2007) 2.Greer, J., Erickson, J.W., Baldwin, J.J., et al.Application of the three-dimensional structures of protein target molecules in structure-based drug designJournal of Medicinal Chemistry37(8)1035-1054(1994) 3.Hunt, C.A., Mallorga, P.J., Michelson, S.R., et al.3-Substituted thieno[2,3-b][1,4]thiazine-6-sulfonamides. A novel class of topically active carbonic anhydrase inhibitorsJournal of Medicinal Chemistry37(2)240-247(1994) 4.Loftsson, T., Jansook, P., and StefÁnsson, E.Topical drug delivery to the eye: DorzolamideActa. Ophthalmol.90(7)603-608(2012) 5.Cheng, J.W., Cheng, S.W., Gao, L.D., et al.Intraocular pressure-lowering effects of commonly used fixed-combination drugs with Timolol: A systematic review and meta-analysisPLoS One7(9)45079(2012)