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N-Desmethylclomipramine (hydrochloride)

(Synonyms: 去甲氯丙咪嗪盐酸,Desmethylclomipramine hydrochloride) 目录号 : GC44352

An Analytical Reference Material

N-Desmethylclomipramine (hydrochloride) Chemical Structure

Cas No.:29854-14-6

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产品描述

N-Desmethylclomipramine (hydrochloride) is an analytical reference material that is an active metabolite of clomipramine . This product is intended for research and forensic applications. This product is a qualified Reference Material (RM) that has been manufactured and tested to meet ISO/IEC 17025 and ISO Guide 34 guidelines. These materials are tested using validated analytical methods on qualified instrumentation to ensure traceability of measurements. All traceable RMs may be distinguished by their CofAs and can be downloaded below using the batch number located on the product label. For a representative CofA please contact our technical support.

Chemical Properties

Cas No. 29854-14-6 SDF
别名 去甲氯丙咪嗪盐酸,Desmethylclomipramine hydrochloride
Canonical SMILES ClC1=CC2=C(C=C1)CCC3=C(C=CC=C3)N2CCCNC.Cl
分子式 C18H21ClN2•HCl 分子量 337.3
溶解度 DMSO : 25 mg/mL (74.12 mM; Need ultrasonic) 储存条件 Store at -20°C
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1 mM 2.9647 mL 14.8236 mL 29.6472 mL
5 mM 0.5929 mL 2.9647 mL 5.9294 mL
10 mM 0.2965 mL 1.4824 mL 2.9647 mL
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Research Update

Metabolism of clomipramine in a Japanese psychiatric population: hydroxylation, desmethylation, and glucuronidation

Neuropsychopharmacology 1995 Jul;12(4):323-33.PMID:7576009DOI:10.1016/0893-133X(94)00098-K.

We measured the concentrations of clomipramine and its metabolites, N-Desmethylclomipramine, 8-hydroxy-N-desmethylclomipramine, 8-hydroxyclomipramine by high-performance liquid chromatography in 108 Japanese psychiatric patients receiving clomipramine hydrochloride PO. The concentrations of the glucuronide conjugates of 8-hydroxyclomipramine and 8-hydroxy-N-desmethylclomipramine were assayed via enzymatic hydrolysis. Although there were large interindividual variations of concentrations of parent, intermediate metabolic compounds, and glucuronide conjugates, significant positive correlations were observed between these drug concentrations and daily doses of clomipramine hydrochloride (mg/kg body weight). Although the metabolic ratios for desmethylation, hydroxylation, and glucuronidation that were calculated from steady-state drug concentrations varied substantially with 36-, 14-, and 28-fold interindividual variations, respectively, apparent poor desmethylators, poor hydroxylators, or poor glucuronidators were not found.

Clinical significance of plasma levels of clomipramine, its hydroxylated and desmethylated metabolites: prediction of clinical outcome in mood disorders using discriminant analysis of therapeutic drug monitoring data

J Affect Disord 1993 Dec;29(4):267-79.PMID:8126313DOI:10.1016/0165-0327(93)90017-e.

We measured the plasma concentrations of clomipramine and its metabolites, N-desmethylclompiramine, 8-hydroxy-N-desmethylclomipramine, 8-hydroxyclomipramine in 65 depressed patients with subtypes of DSM-III-R mood disorders receiving clomipramine hydrochloride. There were large interindividual variations in the concentrations of the parent and each of the metabolic compounds, though the overall correlations between drug concentrations and daily doses of clomipramine were highly significant. Metabolic ratios for both desmethylation and hydroxylation varied by 15-35-fold interindividually. Discriminant analysis of the data from drug concentrations and scores of Global Assessment of Functioning revealed that it is useful to monitor the concentrations of both desmethylated and hydroxylated metabolites in order to predict the clinical effects of clomipramine.

Interindividual variations of desmethylation and hydroxylation of clomipramine in an Oriental psychiatric population

J Clin Psychopharmacol 1993 Jun;13(3):181-8.PMID:8354734doi

We measured the concentrations of clomipramine and its metabolites, N-Desmethylclomipramine, 8-hydroxy-N-desmethylclomipramine, and 8-hydroxyclomipramine in plasma in 92 Japanese psychiatric patients receiving clomipramine hydrochloride (Anafranil, Ciba-Geigy Japan Limited, Takarazuka, Japan) by high-performance liquid chromatography. Although there were large interindividual variations of total drug concentrations and concentrations of parent or intermediate metabolic compounds in plasma, significant positive correlations were observed between these drug concentrations and daily doses of clomipramine hydrochloride (milligrams per kilogram of body weight). The metabolic ratios for both desmethylation and hydroxylation varied substantially with 30- to 90-fold interindividual variations. Frequency distribution histograms and probit analyses of these parameters identified only one possible poor hydroxylator but no poor desmethylator of clomipramine. These results suggest that there are large interindividual variations of capacities for hydroxylation and desmethylation of clomipramine in the Oriental population and that therapeutic drug monitoring is essential in clinical practice to reduce the adverse effects of clomipramine and to prevent poor response to clomipramine.

[Clinical significance of plasma levels of clomipramine and its desmethylated and hydroxylated metabolites]

Yakubutsu Seishin Kodo 1993 Aug;13(4):239-49.PMID:8237141doi

Concentrations of clomipramine and its metabolites, N-Desmethylclomipramine (DC), 8-hydroxy-N-desmethylclomipramine (HDC) and 8-hydroxyclomipramine (HC), in plasma were determined in 99 patients treated with clomipramine hydrochloride. Doses patients received were not fixed but titrated according to their clinical severity and response to the treatment. Large interindividual variations were present in the concentrations of parent or each metabolic compounds in plasma, however, strong correlations existed between these drug concentrations and daily doses of clomipramine (0.40-5.10 mg/kg of body weight) (r = 0.62-0.80). Metabolic ratios for desmethylation and those for hydroxylation were calculated from these data, and revealed very large inter-individual variations of 30-36 fold and 10-96 fold, respectively. Pharmacological data from 65 of these patients with DSM-III-R mood disorders were analyzed by discriminant analysis using the scores of Global Assessment of Functioning. The overall prediction value for responder or nonresponder was calculated as 70% 2 wk after the initiation of pharmacotherapy. Concentrations of hydroxylated metabolites in plasma does contribute as much to the prediction of clinical response to clomipramine as desmethylated metabolites.