Summary
In 24 hr urine of rats orally given 150 mg/kg of 3-hydrazino-6-[bis-(2-hydroxyethyl)amino] pyridazine dihydrochloride (DL 150), no unchanged compound was detected. Three metabolites, less polar than DL 150, were isolated, their structures assigned by UV, MS, IR and1H NMR spectroscopies, and confirmed by synthesis.
They are: 3-bis-(2-hydroxyethyl)aminoJ-6-isopropoxypyridazine (1); 3-[bis-(2-hydroxyethyl)amino] pyridazine (2); 3-methyl-6-[bis-(2-hydroyethyl)amino]-s-triazolo[4, 3-b]pyridazine (3).
The metabolism of DL 150 in the rat follows some of the metabolic pathways reported for hydralazine.
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References
Bellasio E., Parravicini F. and Testa E. (1969): Sintesi di 3-idrazinopiridazine con sostituenti basici in posizione 6, dotate di attivita ipotensiva. II Farmaco, Ed. Sci.,24, 919–929.
Baldoli E., Sardi A., Dezulian V., Capellini M. and Bianchi G. (1973): On the pharmacology of 3-hydrazino-6-[N, N-bis(2-hydro xyethyl)amino-pyridazine-dihydrochloride (L 6150). Arzneim. Forsch.,23, 1591–1595.
Pasotti C., Nicrosini F., Marchetti M., Manzini A. and Nicolis F.B. (1976): Bioassay of the vasodepressor and cardiostimulatory effects of hydralazine and pyridazine derivative (DL 150) in hypertensive patients. II Farmaco, Ed. Pr.,31, 453–462.
Bellasio E. and Campi A. (1978): Synthesis of three metabolites of 3-hydrazino-6-[bis-(2-hydroxyethyl)amino] pyridazine. A new rearrangement of 3-[(1-methylethyliden)-hydrazino]derivatives. II Farmaco, Ed. Sci.,33, 565–572.
Edwards S. and Marquardt F.H. (1969): The metabolism of 1-hydrazinophthalazine: The correct structure of the pseudo “N-acetyl-l-hydrazinophthalazine”. Hoppe-Seyler’s Z. Physiol. Chem.,350, 85–86.
Haegele K.D., Skrdlant H.B., Robie N.W., Lalka D. and McNay J.L. Jr. (1976): Determination of hydralazine and its metabolites by gas chromatography-mass spectrometry. J. Chromatography,126, 517–534.
Reidenberg M.M., Drayer D., De Marco A.L. and Bello C.T. (1973): Hydralazine elimination in man. Clin. Pharm. Ther.,14, 970–977.
Wagner J., Faigle J.W., Imhof P. and Liehr G. (1977): Metabolism of hydralazine in man. Arzneim. Forsch.,27, 2388–2395.
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Beretta, E., Cristina, T., Ferrari, P. et al. Metabolites of 3-hydrazino-6-[bis-(2-hydroxyethyl) amino]pyridazine dihydrochloride in rat urine. European Journal of Drug Metabolism and Pharmacokinetics 4, 29–33 (1979). https://doi.org/10.1007/BF03189396
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DOI: https://doi.org/10.1007/BF03189396