Phase I metabolism of ganstigmine. Rat, dog, monkey and human liver microsomal extracts investigated by liquid chromatography electrospray tandem mass spectrometry

被引：0

作者：

Catinella, S ^{[1
]}

Pelizzi, N ^{[1
]}

Puccini, P ^{[1
]}

Marchetti, S ^{[1
]}

Zanol, M ^{[1
]}

Acerbi, D ^{[1
]}

Ventura, P ^{[1
]}

机构：

[1] Chiesi Farmaceut SPA, R&D, Pharmacokinet Dept, I-43100 Parma, Italy

来源：

JOURNAL OF MASS SPECTROMETRY | 2001年 / 36卷 / 12期

关键词：

drug metabolism; microsomes; electrospray ionization; acetylcholinesterase inhibitor; Alzheimer;

D O I：

10.1002/jms.228

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Ganstigmine, a new acetylcholinesterase inhibitor, was incubated with rat liver microsomes and the resulting metabolites were identified by high-performance liquid chromatographic/mass spectrometric (HPLC/MS) and HPLC/MS/MS analyses. The results showed the formation of eight main metabolites, among which geneseroline and molecules corresponding to mono-hydroxylated, demethylated and reduced ganstigmine. The metabolic profile drawn for humans, dog and monkey showed a pattern very similar to that of rat: only in the case of liver dog microsomes higher amounts of geneseroline and of a metabolite identified as demethylated and reduced drug were detected. Copyright (C) 2001 John Wiley Sons, Ltd.

引用

页码：1287 / 1293

页数：7

共 13 条

[1] Pharmacokinetics and metabolism of zamifenacin in mouse, rat, dog and man
Beaumont, KC
Causey, AG
Coates, PE
Smith, DA
[J]. XENOBIOTICA, 1996, 26 (04) : 459 - 471
[2] BECKER RE, 1991, CHOLINERGIC BASIS AL, P263
[3] Bowen D.M., 1995, ALZHEIMERS DIS CLIN, P89
[4] DAVIES P, 1976, LANCET, V2, P1403
[5] Cholinergic foundations of Alzheimer's disease therapy
Giacobini, E
[J]. JOURNAL OF PHYSIOLOGY-PARIS, 1998, 92 (3-4) : 283 - 287
[6] LOWRY OH, 1951, J BIOL CHEM, V193, P265
[7] Pietra C, 1999, ALZHEIMER'S DISEASE AND RELATED DISORDERS, P689
[8] SOLUTION AND SOLID-STATE STRUCTURES OF THE (-)-N-HEPTYLCARBAMATE OF GENESEROLINE AND ITS HYDROCHLORIDE SALT
REDENTI, E
DELCANALE, M
AMARI, G
VENTURA, P
BACCHI, A
PELIZZI, G
[J]. JOURNAL OF PHARMACEUTICAL SCIENCES, 1995, 84 (09) : 1126 - 1133
[9] SIMS NR, 1980, LANCET, V1, P333
[10] TESTA B, 1976, DRUGS PHARM SCI, V4

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