The in vitro metabolism of thalicarpine, an aporphine–benzyltetrahydroisoquinoline alkaloid, in the rat

Wu, Wu Nan; McKown, Linda A.

doi:10.1016/s0731-7085(02)00202-9

Cited by 17 publications

(17 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The product ion at m/z 286 suggested strongly that the hydroxylation had occurred on the aliphatic group. Generally, the removal of a water molecule from an aliphatic hydroxyl group is characteristic of the dissociation of the even‐electron cations formed by ESI 9. The characteristic ion at m/z 167 resulted from m/z 185 by H 2 O loss, indicating the presence of a hydroxyl group on the aliphatic ring.…”

Section: Resultsmentioning

confidence: 99%

Characterization of in vitro metabolites of rutaecarpine in rat liver microsomes using liquid chromatography/tandem mass spectrometry

Lee

et al. 2004

Rapid Comm Mass Spectrometry

View full text Add to dashboard Cite

Following incubation of rutaecarpine, a new cyclooxygenase-2 inhibitor, with rat liver microsomes, the structures of the metabolites were characterized by liquid chromatography with tandem mass spectrometry. Nine metabolites corresponding to mono- or dihydroxylated rutaecarpine were formed. Characteristic product ions for the identification of rutaecarpine metabolites were observed at m/z 136, 158 and 286. The loss of water led to the fragment ion at m/z 286, indicating the hydroxylation of the aliphatic ring. The fragment ion at m/z 136 indicated the hydroxylated form of the phenyl group of the quinazolinone moiety, while that at m/z 158 indicated the hydroxylated form of the aromatic ring of the indole moiety.

show abstract

Section: Resultsmentioning

confidence: 99%

Characterization of in vitro metabolites of rutaecarpine in rat liver microsomes using liquid chromatography/tandem mass spectrometry

Lee

et al. 2004

Rapid Comm Mass Spectrometry

View full text Add to dashboard Cite

show abstract

“…M4 is believed to be formed through the oxidation at C-5 and hydrolysis of 22-carboxylic methyl ester catalyzed by hepatic cytochrome P450 enzyme [23,31–35]. Moreover, M4 is also a reactive metabolite that can be successively converted to a glucuronide-conjugate ( M1 ) via further glucuronidation at 22-carboxylic group catalyzed by UDP-glucuronosyltransferases [23].…”

Section: Discussionmentioning

confidence: 99%

Urinary metabolites of isorhynchophylline in rats and their neuroprotective activities in the HT22 cell assay

Chen

Sun

et al. 2014

Fitoterapia

View full text Add to dashboard Cite

Isorhynchophylline is one of the major alkaloids from the Uncaria hook possessing the effects of lowered blood pressure, vasodilatation and protection against ischemia-induced neuronal damage. However, the metabolic pathway of isorhynchophylline has not been fully reported yet. In this paper, the metabolism of isorhynchophylline was investigated in rats. Five metabolites were isolated by using solvent extraction and repeated chromatographic methods, and identified by spectroscopic methods including UV, MS, NMR and CD experiments. Three new compounds were identified as 5-oxoisorhynchophyllic acid-22-O-β-D-glucuronide (M1), 17-O-demethyl-16,17-dihydro isorhynchophylline (M2) and 5-oxoisorhynchophyllic acid (M4) together with two known compounds isorhynchophylline (M0) and rhynchophylline (M3). Possible metabolic pathways of isorhynchophylline are proposed. Furthermore, the activity assay for all the metabolites showed that isorhynchophylline (M0) exhibited potent neuroprotective effects against glutamate-induced HT22 cell death. However, little or weak neuroprotective activities were observed for M1–M4. Our present study is important to further understand its metabolic fate and disposition in humans.

show abstract

“…No sulfate conjugates were detected in the present study. The in vitro metabolic study of thalicarpine, a dimeric aporphine and benzyltetrahydroisoquinoline alkaloid, indicated three phase I pathways, including N-demethylation, aporphine ring oxidation, and benzylic oxidation/reduction (Wu and McKown, 2002). The in vivo metabolic pathways of dicentrine revealed from our study are generally consistent with those observed in thalicarpine and apomor- Based on the HPLC-DAD-MS analysis, all of the metabolites identified were from urine, but neither metabolites nor the parent compound were detected from the feces collected during the same period.…”

Section: Discussionmentioning

confidence: 99%

Metabolism of Dicentrine: Identification of the Phase I and Phase II Metabolites in Miniature Pig Urine

Lai¹,

Kuo²,

Chen³

et al. 2010

Drug Metab Dispos

View full text Add to dashboard Cite

ABSTRACT:The metabolic profile of dicentrine, a selective ␣ 1 -adrenoceptor antagonist with potent antiarrhythmic and antihypertensive activities, in miniature pig urine via oral administration was investigated for the first time. The urine, collected after a single oral administration of dicentrine, was pretreated using solvent extraction and column chromatographic methods to identify the metabolites containing fractions. Twenty-four metabolites (MI-1-9 and MII-1-15), of which 21 compounds are new, were identified by mass spectrometry and high-performance liquid chromatography-diode array detector solid-phase extraction-NMR techniques. Of these, 14 metabolites (MI-5, MII-1 and 2, and MII-5-15) were further isolated for structure confirmation. The phase I metabolic transformations of dicentrine were found to be N-demethylation, N-oxidation, O-demethylation (9,10-OMe), O,O-demethylenation (1-OCH 2 O-2), and hydroxylation at the benzylic (C-4) and the aromatic (C-3) positions, whereas those for the phase II were O-glucuronidation and O-glucosylation of the phenolic group of the phase I metabolites.

show abstract

The in vitro metabolism of thalicarpine, an aporphine–benzyltetrahydroisoquinoline alkaloid, in the rat

Cited by 17 publications

References 8 publications

Characterization of in vitro metabolites of rutaecarpine in rat liver microsomes using liquid chromatography/tandem mass spectrometry

Characterization of in vitro metabolites of rutaecarpine in rat liver microsomes using liquid chromatography/tandem mass spectrometry

Urinary metabolites of isorhynchophylline in rats and their neuroprotective activities in the HT22 cell assay

Metabolism of Dicentrine: Identification of the Phase I and Phase II Metabolites in Miniature Pig Urine

Contact Info

Product

Resources

About