Pharmacological uses and perspectives of heavy water and deuterated compounds

Canadian Journal of Physiology and Pharmacology

Volumn 77, Issue 2, 1999, Pages 79-88

  Kushner, D J ^a   Baker, Alison ^a   Dunstall, T G ^b  

^a UNIVERSITY OF TORONTO   (Canada)

^b ONTARIO HYDRO TECHNOLOGIES   (Canada)

Author keywords

D2O; Deuterium; Deuterium isotope effects; Heavy water

Indexed keywords

1 AZIRIDINO 3 (2 NITRO 1 IMIDAZOLYL) 2 PROPANOL; 4 FLUORO DEXTRO PHENYLALANINE; ANTIINFECTIVE AGENT; BUTETHAL; CYTOCHROME P450; DEUTERIUM OXIDE; DIAZEPAM; DRUG; INSECTICIDE; LONG CHAIN FATTY ACID; METHOXYFLURANE; OXAZEPAM; PHENAZONE; PHENYLALANINE DERIVATIVE; PIMONIDAZOLE; SEVOFLURANE; TAMOXIFEN; TYRAMINE; UNCLASSIFIED DRUG;

ANTIMICROBIAL ACTIVITY; DRUG EFFECT; DRUG METABOLISM; DRUG TRANSPORT; GAMMA IRRADIATION; GENOTOXICITY; HUMAN; HYPERTENSION; INSECT; MITOSIS; MOUSE; NEUTRON CAPTURE THERAPY; NONHUMAN; PHARMACOLOGY; PRIORITY JOURNAL; RAT; REVIEW;

EID: 0032772532     PISSN: 00084212     EISSN: None     Source Type: Journal    
DOI: 10.1139/y99-005     Document Type: Review

References (90)

1. Abrahamsson, S., Dinh-Nguyen, N., Hellgren, L.G., and Vincent, J.G. 1982. Patent SE 426011B.
2. Adams, W.H., and Adams, D.G. 1988. Effects of deuteration on hematopoiesis in the mouse. J. Pharmacol. Exp. Ther. 244: 633-639.
3. 2O. Biochem. Int. 1: 41-46.
4. Aldhous, P. 1995. Heavy water helps vaccines keep cool. New Sci. 151: 22.
5. 2O-induced cell excitation. J. Membr. Biol. 115: 123-127.
6. 2O-induced ion channel activation in Characeae at low ionic strength. J. Membr. Biol. 142: 43-53.
7. Archakov, A.I., and Bachmanova, G.I. 1990. Cytochrome P-450 and active oxygen. Taylor and Francis, Inc., Philadelphia.
8. Avery, M.A., Bonk, J.D., and Mehrota, S. 1996. Deuterated antimalarials: synthesis of trideutero-artemisinin, dihydaro-artemisinin, and arteether. J. Labelled Compd. Radiopharm. 38: 249-254.
9. 6-conjugated microspheres. Proc. Natl. Acad. Sci. U.S.A. 88: 1580-1584.
10. Baker, M.T., Ronnenberg, W.C., Jr., Ruzicka, J.A., Chiang, C.-K., and Tinker, J.H. 1993. Inhibitory effects of deuterium substitution on the metabolism of sevoflurane by the rat. Drug Metab. Dispos. 21: 1170-1171.
11. Bauer, A.L., Jachimczak, P., Blesch, A., Baur, J., Hessdorfer, B., Haase, A., and Bogdahn, U. 1995. Selective killing and growth arrest of malignant tumor cells by deuterium oxide. Tumordiagnost. Ther. 16: 61-68. (Paper in German; abstract in Current Contents.)
12. Benedict, M., Pigford, T.H., and Levi, H.W. 1981. Nuclear chemical engineering. 2nd ed. McGraw-Hill, New York.
13. Blake, M.L., Crespi, H.L., and Katz, J.J. 1975. Studies with deuterated drugs. J. Pharm. Sci. 64: 367-391.
14. Carlstedt, B.C., Crespi, H.L., Blake, M.L., and Katz, J.J. 1973. Biosynthesis of deuterated benzylpenicillins. III. Relative antibiotic potency of highly deuterated benzylpenicillin. J. Pharm. Sci. 62: 856-857.
15. Castell, J.V., Martinez, L.A., Miranda, M.A., and Tarrega, P. 1994. A general procedure for isotopic (deuterium) labelling of non-steroidal antiinflammatory 2-arylpropionic acids. J. Labelled Compd. Radiopharm. 34: 93-100.
16. Coward, W.A. 1979. Deuterium method for measuring milk intake in babies. Lancet, 2(8137): 309.
17. Crespi, H.L. 1982. The isolation of deuterated bacteriorhodopsin from fully deuterated Halobacterium halobium. Methods Enzymol. 88: 3-5.
18. Crespi, H.L. 1989. Fully deuterated microorganisms: tools in magnetic resonance and neutron scattering. In Proceedings of the third international symposium on synthesis and applications of isotopically labeled compounds. Innsbruck, Austria, July 17-21, 1988. Edited by T. Baillie and J.R. Jones. Elsevier, Amsterdam. pp. 329-332.
19. Darbyshire, J.F., Gillette, J.R., Nagata, K., and Sugiyama, K. 1994. Deuterium isotope effects on A-ring and D-ring metabolism of testosterone by CYP2C11: evidence for dissociation of activated enzyme-substrate complexes. Biochemistry, 33: 2938-2944.
20. Deraniyagala, S.A., Adediran, S.A., and Pratt, R.F. 1995. β-Secondary and solvent deuterium kinetic isotope effects and the mechanisms of base-and acid-catalyzed hydrolysis of penicillanic acid. J. Org. Chem. 60: 1619-1625.
21. Edington, B.V., Whelan, S.A., and Hightower, L.E. 1989. Inhibition of heat shock (stress) protein induction by deuterium oxide and glycerol: additional support for the abnormal protein hypothesis of induction. J. Cell. Physiol. 139: 219-228.
22. Eisenberg, D., and Kauzmann, W. 1969. The structure and properties of water. Oxford University Press, New York.
23. Elsing, C., Hirlinger, A., Renner, E.L., Lauterburg, B.H., Meier, P.J., and Reichen, J. 1995. Solvent isotope effect on bile formation in the rat. Biochem. J. 307: 175-181.
24. Ferraboschi, P., Grisenti, P., and Santaniello, E. 1994. A facile synthesis of pentadeuterated Domiodol (2-iodomethyl-4-hydroxymethyl-1,3-dioxolane) from glycerol-1,1,2,3,3-d5. J. Labelled Compd. Radiopharm. 34: 303-306.
25. Foster, A.B. 1984. Deuterium isotope effects in studies of drug metabolism. TIPS, 5: 524-527.
26. Foster, A.B. 1985. Deuterium isotope effects in the metabolism of drugs and xenobiotics: implications for drug design. Adv. Drug Res. 14: 1-40.
27. Franklin, T.J., and Snow, G.A. 1989. Biochemistry of antimicrobial action. 4th ed. Chapman and Hall, London.
28. Haon, S., Auge, S., Tropis, M., and Milon, A. 1993. Low cost production of perdeuterated biomass using methylotrophic yeasts. J. Labelled Compd. Radiopharm. 22: 1053-1063.
29. Hatanaka, H. 1989. Clinical results of neutron capture therapy. In Neutron beam design, development, and performance for neutron capture therapy. Basic life sciences. Vol. 54. Edited by O.K. Harling, J.A. Bernard, and R.G. Zamenhof. Pergamon Press, New York. pp. 15-21.
30. Hatanaka, H. 1991. Boron neutron capture therapy for tumors. In Gliomas: principles and practice in neuro-oncology. Edited by A.B.M.F. Karim and E.R. Laws, Jr. Springer-Verlag, Berlin. pp. 233-249.
31. 2H-labelled camptothecins. J. Labelled Compd. Radiopharm. 38: 733-742.
32. 2O) on the polymerization of tubulin in vitro. Biochim. Biophys. Acta, 800: 21-27.
33. Jarman, M., Poon, G.K., Rowlands, M.G., Grimshaw, R.M., Horton, M.N., Potter, G.A., and McCague, R. 1995. The deuterium isotope effect for the α-hydroxylation of tamoxifen by rat liver microsomes accounts for the reduced genotoxicity of [D5-ethyl]tamoxifen. Carcinogenesis, 16: 683-688.
34. Katz, J.J. 1960. The biology of heavy water. Sci. Am. 203: 106-115.
35. Katz, J.J. 1965. Chemical and biological studies with deuterium. 39th Annual Priestly Lecture, Pennsylvania State University, Univesity Park, Pa. pp. 1-110.
36. 2 formation analyzed using hydrogen isotopes. FEBS Lett. 368: 203-206.
37. 2O. J. Phys. Chem. 60: 3132-3144.
38. Kushner, D.J. 1998. What is halophilic and what is archaeal? Proceedings of Workshop on Biology and Geochemistry of Hypersaline Environments, Jerusalem, Israel, June 22-26, 1997. CRC Press, Boca Raton, Fla. pp. 215-225.
39. Kushner, D.J., Baker, A., and Dunstall, T.G. 1997. Biotechnological potential of heavy water and deuterated compounds. Proceedings of Biotechnology Risk Assessment Symposium, Ottawa, Canada, June 23-25, 1996. Edited by M. Levin, C. Grim, and J.S. Angle. University of Maryland Biotechnology Institute Publication 1003. pp. 75-89.
40. Laissue, J.A., Bürki, H., and Berchtold, W. 1982. Survival of tumor-bearing mice exposed to heavy water or heavy water plus methotrexate. Cancer Res. 42: 1125-1129.
41. Laissue, J.A., Altermatt, H.J., Bally, E., and Gebbers, J.O. 1987. Protection of mice from whole body gamma irradiation by deuteration of drinking water: hematologic findings. Exp. Hematol. 2: 177-189.
42. Lamprecht, J., Schroeter, D., and Paweletz, N. 1991. Derangement of microtubule arrays in interphase and mitotic PtK2 cells treated with deuterium oxide (heavy water). J. Cell Sci. 98: 463-473.
43. 7-penicillin. J. Pharm. Sci. 59: 1727-1731.
44. LeMaster, D.M. 1990. Uniform and selective deuteration in two dimensional NMR of proteins. Annu. Rev. Biophys. Biophys. Chem. 19: 243-266.
45. Liepins, A. 1993. Patent US 5223269.
46. Loftus, N.J., Laird, W.J.D., Steel, G.T., Wilks, M.F., and Woollen, B.H. 1993. Metabolism and pharmacokinetics of deuterium-labelled di-2-(ethylhexyl)adipate (DEHA) in humans. Food Chem. Toxic. 31: 609-614.
47. Mabic, S., and Castagnoli, N., Jr. 1996. Regioselective synthesis of deuterated analogs of the neurotoxin MPTP. J. Labelled Compd. Radiopharm. 38: 255-262.
48. 2O on the microtubular components and needle-like form of heliozoan axopods: a pressure-temperature analysis. J. Cell. Physiol. 77: 187-194.
49. Mazier, M.J.P., and Jones, P.J.H. 1997. Diet fat saturation and feeding state modulate rates of cholesterol synthesis in normolipidemic men. J. Nutr. 127: 332-340.
50. McCarty, L.P., Malek, R.S., and Larsen, E.R. 1979. The effects of deuteration on the metabolism of halogenated anaesthetics in the rat. Anesthesiology, 51: 106-110.
51. Merck and Co., Inc. 1977. US Patent 4028405.
52. Miller, A.T., and van Alstyne, H.M. 1994. Heavy water: a distinctive and essential component of CANDU. Atomic Energy of Canada Ltd. Rep. 10962, June 1994.
53. Mosberg, H.I., Omnaas, J.R., Ramalingam, K., and Woodard, R.W. 1987. Synthesis of deuterium labelled pencillamine and its use for the assignment of the 1H NMR spectra of two cyclic enkephalin analogs. J. Labelled Compd. Radiopharm. 24: 1265-1271.
54. Munro, L.H., Gurton, G., and Kelly, F.J. 1997. Plasma RRR -tocopherol concentrations are lower in smokers than in non-smokers after ingestion of a similar oral load of this antioxidant vitamin. Clin. Sci. 92: 87-93.
55. Nelson, S.D. 1983. The use of stable and radioactive isotopes in monitoring reactive metabolite formation. In Synthesis and applications of isotopically labeled compounds. Proceedings of an international synposium. Edited by W.P. Duncan and A.B. Susan. Kansas City, Mo., June 6-11, 1982. Elsevier, Amsterdam. pp. 89-94.
56. Nona, D.A., Blake, M.I., Crespi, H.L., and Katz, J.J. 1968. Effect of deuterium oxide on the culturing of Penicillium janczewskii. III. Antifungal activity of fully deuterated griseofulvin. J. Pharm. Sci. 57: 1993-1995.
57. Northrop, D.B. 1982. Deuterium and tritium kinetic isotope effects on initial rates. Methods Enzymol. 87: 607-625.
58. Paterson, Y., Englander, S.W., and Roder, H. 1990. An antibody binding site on cytochrome c defined by hydrogen exchange and two dimensional NMR. Science (Washington, D.C.), 249: 755-759.
59. 2+ channel. Nature (London), 329: 243-246.
60. Rae, H.K. 1991. Canada's heavy water story. In Chemical engineering in Canada: a historical perspective. Edited by L.W. Shemilt. Canadian Society of Chemical Engineering, Ottawa, Ont. pp. 334-361.
61. 2O) on the functional activity of human platelets. Haemostasis, 15: 157-163.
62. Rodewald, L.E., Maiman, L.A., Foye, H.R., Borch, R.F., and Forbes, G.B. 1989. Deuterium oxide as a tracer for measurement of compliance in pediatric clinical drug trials. J. Pediatr. 114: 885-891.
63. 2 in liquid water as determined by time-resolved infrared luminescence measurements. J. Am. Chem. Soc. 104: 5541-5543.
64. Scobie, M., Bew, S.P., and Threadgill, M.D. 1994. Labelled compounds of interest as antitumour agents. Part 4. Deuteration and tritiation of a nitroimidazole carborane designed for BNCY. J. Labelled Compd. Radiopharm. 34: 881-885.
65. Shemin, D. 1987. On the impact on biochemical research of the discovery of stable isotopes: the outcome of the serendipic meeting of a refugee with the discoverer of heavy isotopes at Columbia University. Anal. Biochem. 161: 365-369.
66. Silvestro, L., Lanzarotti, E., Marchi, E., Gori, M., Pescador, R., Ferro, L., Milani, M.R., da Col, R., and Coppini, A. 1994. Human pharmacokinetics of glycosoaminoglycans using deuterium-labeled and unlabeled substances: evidence for oral absorption. Semin. Thromb. Hemostasis, 20: 281-292.
67. Soderlund, D.M., and Blomquist, J.R. 1990. Molecular mechanisms of insecticide resistance. In Pesticide resistance in arthropods. Edited by R.T. Roush and B.E. Tabashnik. Chapman and Hall, New York. pp. 58-96.
68. Sollott, S.J., Cheng, L., Pauly, R.R., Jenkins, G.M., Monticone, R.E., Kuzuya, M., Froehlich, J.P., Crow, M.T., Lakatta, E.G., Rowinsky, E.K., and Kinsella, J.L. 1995. Taxol inhibits neointimal smooth muscle cell accumulation after angioplasty in the rat. J. Clin. Invest. 95: 1869-1876.
69. Spielmann, H., and Nau, H. 1986. Embryotoxicity of stable isotopes and use of stable isotopes in studies of teratogenetic mechanisms. J. Clin. Pharmacol. 26: 474-480.
70. Thomas, A.F. 1971. Deuterium labeling in organic chemistry. Appleton-Century Crofts, New York.
71. Thomson, J.F. 1963. Biological effects of deuterium. Pergamon Press, Macmillan, New York.
72. Tsuzuki, H., Harada, T., Mukumoto, M., Mataka, S., Tsukinoki, T., Kakinami, T., Nagano, Y., and Tashiro, M. 1996. Ultrasound-assisted reduction of cyanides to deuterated alipathic amines. J. Labelled Compd. Radiopharm. 38: 385-394.
73. Unno, K., and Okada, S. 1994. Deuteration causes the decreased induction of heat-shock proteins and increased sensitivity to heat denaturation of proteins in Chlorella. Plant Cell Physiol. 35: 197-202.
74. Unno, K., Busujima, H., Shimba, S., Narita, K. and Okada, S. 1987. Characteristics of growth and deuterium incorporation in Chlorella ellipsoidea grown in deuterium oxide. Chem. Pharm. Bull. 36: 1828-1833.
75. Unno, K., Shimba, S., and Okada, S. 1989. Modification of thermal response of Chlorella ellipoidea by deuteration. Chem. Pharm. Bull. 37: 3047-3049.
76. Urey, H.C., Brickwedde, F.G., and Murphy, G.M. 1932. A hydrogen isotope of mass 2. Phys. Rev. 39: 164.
77. 2O medium interact in affecting the expression of radiation-induced potentially lethal damage. Int. J. Radiat. Biol. 60: 647-655.
78. Vanatulu, K., Paalme, T., Vilu, R., Burkhardt, N., Jünemann, R., May, R., Rühl, M., Wadzack, J., and Nierhaus, K.H. 1993. Large-scale preparation of fully deuterated cell components: ribosomes from Escherichia coli with high biological activity. Eur. J. Biochem. 216: 315-321.
79. van Beerendonk, G.J.M., Nivard, M.J.M., Vogel, E.W., Nelson, S.D., and Meerman, J.H.N. 1995. Genotoxicity of the flame retardant tris(2,3-dibromopropyl)phosphate in the rat and Drosophila: effects of deuterium substitution. Carcinogenesis, 15: 1197-1202.
80. Vandenheuvel, W.J.A. 1983. The use of stable and radioactive isotopes in drug metabolism studies. In Synthesis and applications of isotopically labeled compounds. Proceedings of an international synposium. Edited by W.P. Duncan and A.B. Susan. Kansas City, Mo. June 6-11, 1982. Elsevier, Amsterdam, pp. 77-82.
81. van Langenhove, A. 1986. Isotope effects: definitions and consequences for pharmacologic studies. J. Clin. Pharmacol. 26: 383-389.
82. Vasdev, S., Gupta, I.P., Sampson, C.A., Longerich, L., and Parai, S. 1993. Deuterium oxide normalizes blood pressure and elevated cytosolic calcium in rats with ethanol-induced hypertension. Can. J. Cardiol. 9: 802-808.
83. Vasdev, S., Prabhakaran, V.M., Whelan, M., Ford, C.A., Longerich, L., and Parai, S. 1994. Fructose-induced hypertension, hyperglyceridemia and elevated cytosolic calcium in rats: prevention by deuterium oxide. Artery, 21: 124-12.
84. Vasilescu, V., and Katona, E. 1986. Deuteration as a tool in investigating the role of water in the structure and function of excitable membranes. Methods Enzymol. 127: 662-678.
85. Wallace, S.A., Mathur, J.N., and Allen, B.J. 1995. The influence of heavy water on boron requirements for neutron capture therapy. Med. Phys. 22: 585-590.
86. 3H isotopomers of RSU 1069 and Ro 03-8799 (Pimonidazole). J. Labelled Compd. Radiopharm. 28: 257-264.
87. 131J-markierten N-(alkyl)-amphetaminen nach deuterierung. J. Labelled Compd. Radiopharm. 27: 1143-1155.
88. Yang, S.K., Tang, R., and Pu, Q.-L. 1996. Synthesis of 3-deuterated diazepam and nordiazepam and their use in synthesis of other 3-deuterated derivatives. J. Labelled Compd. Radiopharm. 38: 753-760.
89. Yokogaki, S., Unno, K., Oku, N., and Okada, S. 1995. Chaperonin-repairable subtle incompleteness of protein assembly induced by a substitution of hydrogen with deuterium: effect of GroE on deuterated ribulose 1,5-bisphosphate carboxylase. Plant Cell Physiol. 36: 419-423.
90. 2O)-induced shape changes, movements and F-actin redistribution in human neutrophil granulocytes. Eur. J. Cell Biol. 47: 320-326.