Enzymatic and nonenzymatic hydrolysis of D,L-dipivefrin.
D,L-dipivefrin hydrochloride was administered bilaterally to rabbit eyes five or 150 minutes after unilateral application of a cholinesterase inhibitor. Aqueous humor levels of D,L-epinephrine, measured 30 minutes later by high-performance liquid chromatography, were not significantly different in the two eyes. Nonenzymatic conversion of D,L-dipivefrin to D,L-epinephrine was measured in tissue-free (pH 7.4) solutions; after three hours less than 1% of D,L-dipivefrin became D,L-epinephrine. Homogenates of corneal epithelium were 16 times more effective in converting D,L-dipivefrin to D,L-epinephrine than after heat-inactivation. The ocular hypotension produced by 0.25% D,L-dipivefrin eyedrops was unaffected by prior administration of 0.25% echothiophate iodide eyedrops provided the D,L-dipivefrin was administered after the echothiophate-induced ocular hypertensive phase. It was concluded that D,L-dipivefrin was converted to D,L-epinephrine in vivo primarily by enzymatic hydrolysis and that cholinesterase inhibitors did not affect this conversion.
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001082:Aqueous Humor / Q000378:metabolism; D002384:Catalysis; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000378:metabolism; D004456:Echothiophate Iodide / Q000494:pharmacology; D004837:Epinephrine / Q000031:analogs & derivatives* / Q000378:metabolism; D005123:Eye / Q000378:metabolism*; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007429:Intraocular Pressure; D010830:Physostigmine / Q000494:pharmacology; D011817:Rabbits
D002800:Cholinesterase Inhibitors; C015173:dipivefrin; D010830:Physostigmine; D004456:Echothiophate Iodide; D004837:Epinephrine