Abstract
(±)-Higenamine is known as a cardiotonic principle of aconite root (root ofAconitum spp., Ranunculaceae). A simple and sensitive detection method for higenamine was developed by using gas chromatography-mass spectrometry (GC/MS). The recovery of higenamine after extraction and concentration with XAD-2 resin column was around 95% from rat biological fluids such as bile, plasma and urine. The limits of detection of higenamine in these biological fluids were approximately 0.1 ng/ml each. It has well been suggested that tetrahydroisoquinolines possessing catechol moiety such as higenamine should be subjected to the catechol-O-methyl transferase (COMT) activityin vivo. We detected two major peaks of presumed metabolites of higenamine in the total ion chromatogram obtained from the rat urine sample after the oral administration of (±)-higenamine. The scan mass spectrum of one of the metabolites coincided with those obtained from coclaurine (C6-O-methyl higenamine) and those of the other metabolite are suggestive of isococlaurine (C7-O-methyl higenamine).
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References Cited
Cashaw, J. L., Geraghty, C. A., McLaughlin, B. R. and Davis, V. E., A Method for determination of subpicomole concentration of tetrahydropapaveroline in rat brain by high performance liquid chromatography with electrochemical detection.Anal. Biochem., 162, 274–282 (1987).
Chang, K. C., Lim, J. K., Park, C. W. and Kim, M. S., Studies on the mechanism of positive iontropic action of higenamine.Kor. J. Pharmacol., 17, 7–15 (1981).
Chang, K. C., Yun-Choi, H. S., Lim, J. K. and Park, C. W., Synthesis of higenamine, A cardiotonic principle of aconite root.Arch. Pharm. Res., 7, 133–136 (1984).
Huang, L. Z., Zhang, D. Y. and Wang, C. Y., Synthesis of higenamine.Acta Pharmaceutica Sinica, 16, 931–933 (1981).
Kim, N. S., Hong, C. Y., Park, C. W. and Lim, J. K., An experimental study on the adrenergic effect of higenamine in rabbit cardiovascular system.Kor. Circ. J., 16, 1–18 (1986).
Kosuge, T., Yokota, M. and Nagasawa, M., Studies on cardiac principle in aconite roots I. Isolation and structural determination of higenamine.Yakugaku Zasshi., 98, 1370–1375 (1978).
Leboeuf, M. and Cave, A., Isolement de L’Higenamine a Partir de L’Annona Squamosa; Interet des resines adsorbantes macromoleculaires en chimie vegetale extractive.J. Nat. Prod., 44, 53–60 (1981).
Park, C. W., Chang, K. C. and Lim, J. K., Effects of higenamine on isolated heart adrenoceptor of rabbit.Arch. Int. Pharmacodyn, 267, 279–288 (1984).
Park, S. O., Hong, C. Y., Park, S. W. and Yun-Choi, H. S., Determination of blood concentration of higenamine by high pressure liquid chromatography.Arch. Pharm. Res., 10, 60–66 (1987).
Rozwadowska, M. D., Chrzanowska, M., Brossi, A., Creveling, C. R., Bembenek, M. E. and Abell, C. W., Mammalian alkaloids: O-methylation of (S)- and (R)-dideoxynorlandanosoline-1-carboxylic acid by catechol O-methyl-transferase and identification of a yellow pigment obtained at physiological pH.Helvetica Chimica Acta., 71, 1598–1607 (1988).
Sekine, Y., Creveling, C., Bell, M. and Brossi, M., 46. Mammalian alkaloids: O-methylation of (±)-norcoclaurine-1-carboxylic acid and related isoquionlines including (S)- and (R)-norcoclaurine with14C-labeled S-adenoxyl-L-methionine in presence of mammalian catechol O-methyltransferase.Hervetica Chimica Acta., 73, 426–432 (1990).
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Ryu, JC., Song, YS., Kim, M. et al. Identification of higenamine and its metabolites in rat by gas chromatography/mass spectrometry. Arch. Pharm. Res. 16, 213–218 (1993). https://doi.org/10.1007/BF02974485
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DOI: https://doi.org/10.1007/BF02974485