Abstract
This is the first report of nerve terminal degeneration within the iris following topical dipivalyl epinephrine 0.1% treatment. A quantitative comparison of the effects of topically applied epinephrine 2%, dipivalyl epinephrine 0.1%, and placebo vehicle on the nerve terminals within the iris of a rat was made using electron microscopy and a catecholamine radioenzyme assay. Thirty-nine rats were divided into these 3 treatment groups and treated for 10 weeks, after which they were killed and studied. Both the epinephrine 2%- and dipivalyl epinephrine 0.1%-treated groups showed greater nerve terminal degeneration compared with the placebotreated group (P<0.05). The epinephrine-treated group showed greater nerve terminal degeneration than the dipivalyl epinephrine-treated group. The clinical significance of these observations is unknown. It is impossible to decide whether these degenerative changes are related unavoidably to a desired therapeutic effect or to an undesirable, potentially avoidable, toxic side effect.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Azevedo I, Osswald W (1977) Adrenergic nerve degeneration induced by condensation products of adrenaline and acetaldehyde. Naunyn Schmiedebergs Arch Pharmacol 300:139–144
Flach AJ (1984) Ophthalmic clinical pharmacology review: epinephrine and the therapy of the glaucomas. J Toxicol 3:31–51
Flach AJ, Kramer SG (1980) Supersensitivity to topical epinephrine after long-term epinephrine therapy. Arch Ophthalmol 98:482–483
Flach AJ, Wood IS (1978) An electron microscopic study of degeneration of nerve terminals after administration of epinephrine. Exp Eye Res 27:377–385
Flach AJ, Peterson IS, Roizen MF, Wood IS (1983) Ptosis in the rat following topically administered 2% epinephrine. Invest Ophthalmol Vis Sci 24:766–771
Flach AJ, Peterson JS, Wood IS, Roizen MF (1981) Degeneration of nerve terminals in cats following systemic epinephrine: depletion of tissue norepinephrine correlated with ultrastructural changes. Exp Eye Res 32:389–394
Jonsson G (1980) Chemical neurotoxins as denervation tools in neurobiology. Annu Rev Neurosci 3:169–187
Kohn AN, Moss AP, Hargett NA, Ritch R, Smith H, Podos SM (1979) Clinical comparison of dipivalyl epinephrine and epinephrine in the treatment of glaucoma. Am J Ophthalmol 87:196–201
Krieglstein GK, Leydhecker W (1978) The dose-response relationships of dipivalyl epinephrine in open-angle glaucoma. Albrecht von Graefe's Arch Ophthalmol 205:141–146
Neufeld AH (1981) Epinephrine and timolol: how do these drugs lower intraocular pressure? Annu Ophthalmol 13:1109–1111
Neufeld AH, Zawistowski KA, Page ED, Bromberg BB (1978) Influences on the density of beta-adrenergic receptors in the cornea and iris-ciliary body of the rabbit. Invest Ophthalmol Vis Sci 17:1069–1075
Sears ML (1966) The mechanism of action of adrenergic drugs in glaucoma. Invest Ophthalmol 5:115–119
Shields MB (1982) Adrenergic drugs: a study of glaucoma. Williams and Wilkins, Baltimore, pp 405–425
Tse DC, McCreery RL, Adams RN (1976) Potential oxidative pathways of brain catecholamines. J Med Chem 19:37–40
Author information
Authors and Affiliations
Additional information
Correspondence to: A.J. Flach
Rights and permissions
About this article
Cite this article
Flach, A.J., Donahue, M.E. & Wood, I.S. Nerve terminal degeneration in the rat iris observed following chronic topical 2% epinephrine and 0.1% dipivalyl epinephrine: a quantitative comparison of electron microscopic observations and tissue norepinephrine levels. Graefe's Arch Clin Exp Ophthalmol 230, 575–579 (1992). https://doi.org/10.1007/BF00181781
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00181781