AFTER CHRONIC ADMIN OF...CHLORCYCLIZINE TO RATS, THE TISSUES CONTAINED DRUG METABOLITES, IN WHICH PIPERAZINE RING FISSION BY MULTIPLE OXIDATIVE N-DEALKYLATION HAD OCCURRED TO GIVE A SUBSTITUTED ETHYLENEDIAMINE. ... ACCUM OF N-(P-CHLOROBENZHYDRYL)ETHYLENEDIAMINE WAS FOUND IN RATS, TREATED WITH CHLOROCYCLIZINE.
OXIDATIVE N-DEALKYLATION IS MAIN METAB PATHWAY OF BENZHYDROLPIPERAZINES... /CHLORCYCLIZINE IS/ TRANSFORMED INTO...NORCHLORCYCLIZINE... CHLORCYCLIZINE N-OXIDE DOES NOT LIE ON METAB PATHWAY CONNECTING CHLORCYCLIZINE WITH NORCHLORCYCLIZINE, BUT RATS & MAN TREATED WITH CHLORCYCLIZINE EXCRETE CHLORCYCLIZINE N-OXIDE IN URINE.
来源:Hazardous Substances Data Bank (HSDB)
代谢
在大鼠中产生去甲基氯环利定。/来自表格/
YIELDS DEMETHYLCHLORCYCLIZINE IN RAT. /FROM TABLE/
参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 用于研究药物诱导肝损伤的FDA批准药物标签，药物发现今日，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：按发展药物诱导人类肝损伤风险排名的最大参考药物清单。药物发现今日2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
SEVERAL REVIEWS BRIEFLY MENTIONED THAT ANTIHISTAMINES INTERFERE WITH ANTICOAGULANT THERAPY; HOWEVER, NO DOCUMENTATION WAS PRESENTED, NO CASE REPORTS OF ANTICOAGULATION PROBLEMS CAUSED BY ANTIHISTAMINES HAVE APPEARED. /ANTIHISTAMINES/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
吸收
易于口服吸收并在全身广泛分布。通过N-脱甲基化代谢形成去甲氯环利定，并通过N-氧化代谢。
Readily absorbed after oral administration and widely distributed throughout the body. Metabolised by N-demethylation to form norchlorcyclizine and by N-oxidation.
Slowly excreted in the urine; measurable amounts of norchlorcyclizine have been detected in the urine for up to 3 weeks after the cessation of chronic oral administration. About 0.5% of a single dose is excreted in the urine as the N-oxide.
After a single oral dose of 2 mg/kg to 4 subjects, average peak plasma concentrations of about 0.05 mg/L and 0.03 mg/L were attained in 5 h for unchanged drug and norchlorcyclizine, respectively. After oral administration of 50 mg 3 times a day for 6 days, plasma concentrations of norchlorcyclizine of 0.05 to 0.11 mg/L were reported on the first day after the cessation of treatment and plasma concentrations of 0.02 to 0.04 mg/L were found on the 10th day after cessation of treatment [Kuntzman et al. 1973].
...RATS & MAN TREATED WITH CHLORCYCLIZINE EXCRETE CHLORCYCLIZINE N-OXIDE IN URINE. BENZHYDROLPIPERAZINES & THEIR N-DEALKYLATION PRODUCTS ARE DISTRIBUTED IN ALL TISSUES OF RATS & ARE TRANSFERRED TO FETUS.
...NORCHLORCYCLIZINE IS RETAINED IN HUMANS FOR AT LEAST 20 DAYS AFTER TERMINATION /OF CHLORCYCLIZINE/ THERAPY. .../CHLORCYCLIZINE/ GIVES VERY LOW PLASMA LEVELS SINCE.../IT IS/ MARKEDLY LOCALIZED IN TISSUES, PARTICULARLY LUNG.
[EN] PIPERIDINE AND PIPERAZINE DERIVATIVES AND THEIR USE IN TREATING VIRAL INFECTIONS AND CANCER [FR] DÉRIVÉS PIPÉRIDINE ET PIPÉRAZINE ET LEUR UTILISATION POUR TRAITER LES INFECTIONS VIRALES ET LE CANCER
Disclosed herein are substituted indole cysteinyl leukotriene receptor modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
The present invention relates to substituted tricyclic triazole compounds and compositions comprising substituted tricyclic triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a compound of the invention, or a composition comprising such a compound.
The invention relates to sulfonamide derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes.
More particularly the invention relates to new sulfonamide Nav1.7 inhibitors of formula (I):
or pharmaceutically acceptable salts thereof, wherein Z
1
, R
a
, R
b
, R
1
, R
2
, R
3
, R
4
and R
5
are as defined in the description.
Nav 1.7 inhibitors are potentially useful in the treatment of a wide range of disorders, particularly pain.
该发明涉及磺胺衍生物，其在医学上的应用，含有它们的组合物，其制备方法以及用于这些方法的中间体。
更具体地，该发明涉及公式（I）的新磺胺基Nav1.7抑制剂：
或其药学上可接受的盐，其中Z
1
，R
a
，R
b
，R
1
，R
2
，R
3
，R
4
和R
5
如描述中所定义。
Nav 1.7抑制剂在治疗各种疾病，特别是疼痛方面具有潜在用途。
[EN] COMBINATIONS COMPRISING ALPHA-2-DELTA LIGANDS<br/>[FR] COMBINAISONS CONTENANT DES LIGANDS DE ALPHA-2-DELTA
申请人：PFIZER LTD
公开号：WO2005092318A1
公开（公告）日：2005-10-06
The instant invention relates to a combination, particularly a synergistic combination, of an alpha-2-delta ligand and an atypical antipsychotic, and pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof and their use in the treatment of pain, particularly neuropathic pain.
[EN] VINYL-ARYL DERIVATIVES FOR INFLAMMATION AND IMMUNE-RELATED USES<br/>[FR] DÉRIVÉS VINYL-ARYLÉS UTILISÉES POUR TROUBLES INFLAMMATOIRES ET IMMUNITAIRES
申请人：SYNTA PHARMACEUTICALS CORP
公开号：WO2009017831A1
公开（公告）日：2009-02-05
The invention relates to compounds that are useful as immunosuppressive agents and for treating and preventing inflammatory conditions, allergic disorders, and immune disorders.
