PT  - JOURNAL ARTICLE
AU  - MORRIS S. ZEDECK
AU  - L. B. MELLETT
AU  - EDWARD J. CAFRUNY
TI  - THE DIURETIC EFFECTS OF CYCLOPHOSPHAMIDE AND NORNITROGEN MUSTARD: RELATIONSHIP TO ANTIDIURETIC HORMONE
DP  - 1966 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 550--561
VI  - 153
IP  - 3
4099  - http://jpet.aspetjournals.org/content/153/3/550.short
4100  - http://jpet.aspetjournals.org/content/153/3/550.full
SO  - J Pharmacol Exp Ther1966 Sep 01; 153
AB  - While investigating the physiologic disposition of cyclophosphamide, an alkylating agent, we observed that the drug produces a diuresis in rats and dogs. This investigation was undertaken to establish the nature of the diuresis and to elucidate the mechanism of action of the drug. Nor-nitrogen mustard, a metabolite of cyclophosphamide, also produced a diuretic response. Cyclophosphamide was ineffective in the absence of antidiuretic hormone (ADH), and it appeared that inhibition of the actions of ADH was responsible for the diuresis. Rats were pretreated with cyclophosphamide or nor-nitrogen mustard 2 hr before the administration of a water load and ADH. A partial inhibition of the ADH effect was observed. Drug-treated animals showed a partial inhibition of the effects of ADH released centrally by the administration of nicotine. Administration of solutions of cyclophosphamide or nor-nitrogen mustard incubated with ADH in vitro to water-loaded rats resulted in an antidiuretic effect. The hypotheses concerning the biochemical effects of ADH involve intermediates which possess potential sites for alkylation. Thus, the alkylating agents cyclophosphamide or nor-nitrogen mustard could indirectly inhibit the effects of ADH. While it appears that these alkylating agents inhibit the effects of ADH peripherally, a concomitant inhibition of ADH release or synthesis has not been ruled out. © 1966 by The Williams & Wilkins Co.