Abstract
IT is generally believed that noradrenaline synthesis in postganglionic sympathetic nerves can be suppressed by drugs which inhibit the activities of tyrosine hydroxylase or dopamine β-oxidase1,2, but not by inhibition of aromatic 1-amino acid decarboxylase (AAAD; dopa decarboxylase). We present here evidence that the administration to rats of carbidopa (MK-486; α-methyl-L-dopa-hydrazine), a peripherally acting inhibitor of AAAD3, not only blocks the decarboxylation of exogenous L-dopa (for example, in capillary endothelia within the central nervous system, liver, and kidney4,5), but also suppresses the decarboxylation of endogenous dopa formed from 3H-tyrosine within cardiac sympathetic nerve terminals. As a consequence, the drug inhibits noradrenaline synthesis in this tissue.
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References
Costa, E., et al., Pharmac. Rev., 24, 167–190 (1972).
Weiner, N., Cloutier, G., Bjur, R., and Pfeffer, R. I., Pharmac. Rev., 24, 203–221 (1972).
Lotti, V. J., and Porter, C. C., J. Pharmac. exp. Ther., 172, 406–415 (1970).
Bartholini, G., and Pletscher, A., J. pharm. Pharmac., 21, 323–324 (1969).
Anden, N.-E., Engel, J., and Rubenson, A., Naunyn-Schmiedeberg's Arch. exp. Path. Pharmak., 273, 11–26 (1972).
Waalkes, T. P., and Udenfriend, S., J. Lab. clin. Med., 50, 733–736 (1957).
Kehr, W., Carlsson, A., and Lindqvist, M., Naunym-Schmiedeberg's Arch. exp. Path. Pharmak., 274, 273–280 (1972).
Anton, A. H., and Sayre, D. F., J. Pharmac. exp. Ther., 138, 360–375 (1962).
Udenfriend, S., Zaltzman-Nirenberg, P., Gordon, R., and Spector, S., Molec. Pharmac., 2, 95–105 (1966).
Vickers, A., et al., Drug Metab. Dispos., 2, 9–22 (1974).
Scriabine, A., Ludden, C. T., Stone, C. A., Wurtman, R. J., and Watkins, C. J., Clin. Sci. molec. Med. (in the press).
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WURTMAN, R., WATKINS, C. Suppression of noradrenaline synthesis in sympathetic nerves by carbidopa, an inhibitor of peripheral dopa decarboxylase. Nature 265, 79–80 (1977). https://doi.org/10.1038/265079a0
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DOI: https://doi.org/10.1038/265079a0
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