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Metabolism of DL-Norepinephrine-7-3H in the Guinea Pig treated with Tolbutamide

Naturevolume 193pages577578 (1962) | Download Citation



TOLBUTAMIDE, a drug widely used in the treatment of diabetes, has been reported to relieve pain in a large proportion of patients with angina pectoris and intermittent claudication1. This clinically useful property of tolbutamide has been related to an acceleration of fibrinolytic activity in the blood2. An alteration in vascular tone might account, however, for a similar clinical response. To test this possibility we examined the effect of tolbutamide on the metabolism of norepinephrine, the sympathetic transmitter. Our results indicate that the drug profoundly alters the intermediary metabolism of this neurohormone in animals. Since treatment with sulphonylurea compounds has been reported3 to cause disulphiram-like reactions we thought at first that norepinephrine metabolism might have been affected at the aldehyde dehydrogenase-level. Our experimental results show, however, that tolbutamide and disulphiram act quite differently on norepinephrine metabolism.

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    Nestel, P. J., Lancet, ii, 373 (1959); Fearnley, G. K., Chakrabarti, R., and Vincent, C. T., ibid., ii, 622 (1960). Fearnley, G. R., Amer. J. Cardiol., 6, 371 (1960).

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    Canessa, I., Valienti, S., and Mella, I., Ann. N.Y. Acad. Sci., 74, 752 (1959).

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    Armstrong, M. D., McMillan, A., and Shaw, K. N. F., Biochim. Biophys. Acta, 25, 422 (1957).

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    Smith, A., and Wortis, S. B., Biochem. Pharm., 3, 333 (1960).

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    Weissbach, H., Redfield, B. G., and Udenfriend, S., J. Biol. Chem., 229, 935 (1957).

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  1. Department of Psychiatry and Neurology, and the Department of Medicine, New York University Medical Center, New York

    • A. SMITH
    • , M. FABRYKANT
    • , S. GITLOW


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