Journal Article Central origin of the lenticular opacities induced in mice by opiates Get access A Smith, A Smith Department of Anesthesiology, New York Medical College, New York Search for other works by this author on: Oxford Academic Google Scholar M Karmin, M Karmin Department of Anesthesiology, New York Medical College, New York Search for other works by this author on: Oxford Academic Google Scholar J Gavitt J Gavitt Department of Anesthesiology, New York Medical College, New York Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 18, Issue 8, August 1966, Pages 545–546, https://doi.org/10.1111/j.2042-7158.1966.tb07925.x Published: 12 April 2011 Article history Received: 01 June 1966 Published: 12 April 2011
Opiates, when injected in large doses, induce transient lenticular opacities in mice. In this study it was found that a single previous dose of levorphanol established long-term resistance or tolerance to the lenticular effects of a second dose. However, high concentrations of epinephrine instilled in the eyes of tolerant mice were able to restore the normal lenticular response to parenteral levorphanol. The epinephrine concentrations required for an ED5O response correlated with the size of the first dose of levorphanol. Morphine or methadone, when substituted for the first dose of levorphanol, produced a cross-tolerance to the second dose of levorphanol as measured in terms of an epinephrine concentration. When larger doses of levorphanol were given, short-term tolerance also was observed. This effect developed within 30 min and persisted for up to 8 hr. Lenticular tolerance was found to develop in mice previously treated with reserpine, suggesting that this phenomenon probably does not require adrenergic mediation. Levallorphan was able to prevent the development of long-term tolerance when given in a large dose relative to the dose of levorphanol. The antibiotics actinomycin or puromycin also blocked long-term tolerance development, although neither of these inhibitors of protein synthesis prevented the appearance of short-term tolerance. Evidently, long-term lenticular tolerance to opiates is a complex phenomenon involving a decreased sensitivity to instilled epinephrine that may be related to the formation of an inhibitory protein.
Granular changes are seen in the lens and cornea of some patients given large doses of chlorpromazine.1The changes in the lens resemble the lenticular opacities induced in mice by the administration of narcotics of the morphine class2and by catecholamines.3This report describes the formation in mice of lenticular opacities after chlorpromazine treatment. Attempts to block development of the cataract by sympatholytic compounds are discussed in relation to the effects of these compounds on opacities induced by catecholamines and narcotics.
Materials and Methods
Female Swiss-Webster mice, weighing 20 to 25 gm, were used throughout. All injections were given intraperitoneally in volumes between 0.1 and 0.2 ml except where indicated. Chlorpromazine hydrochloride (molecular weight, 355.3) was used as the commercially available preparation; epinephrine bitartrate (USP) and the levorphanol bitartrate were prepared before each use. The e inephrine solutions were administered in two stages, about 10% of the
