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Teratology and Carbonic Anhydrase Inhibition

Teratology and Carbonic Anhydrase Inhibition Abstract FIVE years ago, Layton and Hallesy1 reported that rats fed acetazolamide in the diet during pregnancy gave birth to offspring in which about 36% had a peculiar but specific postaxial defect confined mainly to the right forepaw. The most common lesion was absence of the fourth and fifth digits and the corresponding metacarpals. At that time, it was not clear to me whether this was due to carbonic anhydrase inhibition or some unknown effect of acetazolamide.2 More recently, we have clarified this point, since it appears that all the potent carbonic anhydrase inhibitors, ethoxzolamide,3 dichlorphenamide,4 methazolamide, and benzolamide (unpublished data by W.M. Layton, W.J. Scott, and T.H.M.) cause identical lesions. The high doses (0.2% to 0.6% in the diet, or several hundred milligrams per kilograms per day) used by Layton and Hallesy1 were necessary because of their drug-diet method and the relatively short half life References 1. Layton WM Jr, Hallesy DW: Deformity of forelimb in rats: Association with high doses of acetazolamide . Science 149:306-308, 1965.Crossref 2. Maren TH: Forelimb deformity in rats: Association with acetazolamide . Science 150:79, 1965.Crossref 3. Wilson JG, Maren TH, Takano K, et al: Teratogenic action of carbonic anhydrase inhibitors in the rat . Teratology 1:51-60, 1968.Crossref 4. Hallesy DW, Layton WM Jr: Forelimb deformity of offspring of rats given dichlorphenamide during pregnancy . Proc Soc Exp Biol Med 126:6-8, 1967.Crossref 5. Maren TH: Carbonic anhydrase, chemistry, physiology, and inhibition . Physiol Rev 47:596-781, 1967. 6. Wilson JG, Fradkin R: Comparison of teratogenic sensitivity of rats and rhesus monkeys . Teratology 2:272, 1969. 7. Layton WM: Teratogenic action of acetazolamide in the golden hamster. Teratology, to be published. 8. Wilk AL: Production of fetal rat malformations by norchlorocyclizine and chlorocyclizine after intra uterine application . Teratology 2:55-65, 1969.Crossref 9. Waddell WJ, Bates RG: Intracellular pH . Physiol Rev 49:285-329, 1969. 10. Neuman WF, Newman MW: The Chemical Dynamics of Bone Mineral . Chicago, University of Chicago Press, 1958. 11. Scott WJ Jr: Effects of intra-uterine administration of acetazolamide in rats . Teratology 3:261-268, 1970.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

Teratology and Carbonic Anhydrase Inhibition

Archives of Ophthalmology , Volume 85 (1) – Jan 1, 1971

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Publisher
American Medical Association
Copyright
Copyright © 1971 American Medical Association. All Rights Reserved.
ISSN
0003-9950
eISSN
1538-3687
DOI
10.1001/archopht.1971.00990050003001
Publisher site
See Article on Publisher Site

Abstract

Abstract FIVE years ago, Layton and Hallesy1 reported that rats fed acetazolamide in the diet during pregnancy gave birth to offspring in which about 36% had a peculiar but specific postaxial defect confined mainly to the right forepaw. The most common lesion was absence of the fourth and fifth digits and the corresponding metacarpals. At that time, it was not clear to me whether this was due to carbonic anhydrase inhibition or some unknown effect of acetazolamide.2 More recently, we have clarified this point, since it appears that all the potent carbonic anhydrase inhibitors, ethoxzolamide,3 dichlorphenamide,4 methazolamide, and benzolamide (unpublished data by W.M. Layton, W.J. Scott, and T.H.M.) cause identical lesions. The high doses (0.2% to 0.6% in the diet, or several hundred milligrams per kilograms per day) used by Layton and Hallesy1 were necessary because of their drug-diet method and the relatively short half life References 1. Layton WM Jr, Hallesy DW: Deformity of forelimb in rats: Association with high doses of acetazolamide . Science 149:306-308, 1965.Crossref 2. Maren TH: Forelimb deformity in rats: Association with acetazolamide . Science 150:79, 1965.Crossref 3. Wilson JG, Maren TH, Takano K, et al: Teratogenic action of carbonic anhydrase inhibitors in the rat . Teratology 1:51-60, 1968.Crossref 4. Hallesy DW, Layton WM Jr: Forelimb deformity of offspring of rats given dichlorphenamide during pregnancy . Proc Soc Exp Biol Med 126:6-8, 1967.Crossref 5. Maren TH: Carbonic anhydrase, chemistry, physiology, and inhibition . Physiol Rev 47:596-781, 1967. 6. Wilson JG, Fradkin R: Comparison of teratogenic sensitivity of rats and rhesus monkeys . Teratology 2:272, 1969. 7. Layton WM: Teratogenic action of acetazolamide in the golden hamster. Teratology, to be published. 8. Wilk AL: Production of fetal rat malformations by norchlorocyclizine and chlorocyclizine after intra uterine application . Teratology 2:55-65, 1969.Crossref 9. Waddell WJ, Bates RG: Intracellular pH . Physiol Rev 49:285-329, 1969. 10. Neuman WF, Newman MW: The Chemical Dynamics of Bone Mineral . Chicago, University of Chicago Press, 1958. 11. Scott WJ Jr: Effects of intra-uterine administration of acetazolamide in rats . Teratology 3:261-268, 1970.Crossref

Journal

Archives of OphthalmologyAmerican Medical Association

Published: Jan 1, 1971

References