Flurazepam is rapidly metabolized and is excreted primarily in the urine. Both hydroxyethyl flurazepam (the major metabolite) and N-desalkyl flurazepam are active. The N-desalkyl metabolite is slowly excreted in the urine as the conjugated form
IT IS METABOLIZED IN LIVER. THE DIETHYLAMINE GROUP IS DESETHYLATED, THEN DEAMINATED, EVENTUALLY TO YIELD ALCOHOL, THE MAJOR METABOLITE IN MAN. ALCOHOL IS CONJUGATED TO FORM THE GLUCURONIDE. THE PHENYL RING IS ALSO HYDROXYLATED AT THE ORTHO POSITION, THEN CONJUGATED. THE HETEROCYCLIC RING IS ALSO HYDROXYLATED. /FLURAZEPAM DIHYDROCHLORIDE/
YIELDS 7-CHLORO-1-(2-ETHYLAMINOETHYL)-5-(2-FLUOROPHENYL)-1,3-DIHYDRO-2H- 1,4-BENZODIAZEPIN-2-ONE IN MAN & IN DOG & YIELDS 7-CHLORO-5-(2-FLUOROPHENYL)-1,3-DIHYDRO-2H-1,4-BENZODIAZEPIN-2-ONE IN MAN. /FROM TABLE/
YIELDS 7-CHLORO-1-(N-ETHYL-N-(2-HYDROXYETHYL)AMINOETHYL)-5-(2-FLUOROPHENYL)- 1,3-DIHYDRO-2H-1,4-BENZODIAZEPIN-2-ONE IN MAN & YIELDS 7-CHLORO-5-(2-FLUOROPHENYL)-1,3-DIHYDRO-3-HYDROXY-2H-1,4-BENZODIAZEPIN-2-ONE IN DOGS. /FROM TABLE/
AFTER CHRONIC ORAL DOSES OF FLURAZEPAM TO HUMAN SUBJECTS, UNCHANGED DRUG COULD NOT BE DETECTED IN BLOOD, & MAJOR CMPD PRESENT WAS N-DEALKYL-FLURAZEPAM. BIOLOGICAL HALF-LIFE OF THIS METABOLITE RANGED FROM 47-100 HR.
Benzodiazepines bind nonspecifically to bezodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.
Flurazepam, as with other benzodiazepines, is rarely associated with serum ALT or alkaline phosphatase elevations, and clinically apparent liver injury is rare. Only a few case reports of acute liver injury from flurazepam have been published and mostly before 1980. The latency to onset of acute liver injury varied between 2 to 6 months and the pattern of liver enzyme elevations was cholestatic. The injury was usually mild-to-moderate in severity and self-limited in course. Fever and rash were not described nor autoantibody formation. Similar rare cases of self-limited, mild-to-moderate, cholestatic liver injury have been reported with other benzodiazepines including alprazolam, chlordiazepoxide, clonazepam, diazepam, lorazepam, and triazolam.
Flurazepam is rapidly metabolized and is excreted primarily in the urine. Less than 1% of the dose is excreted in the urine as N1-desalkyl-flurazepam.
来源:DrugBank
吸收、分配和排泄
HYPNOTIC, FLURAZEPAM HYDROCHLORIDE, HAS BEEN SHOWN TO BE RAPIDLY & COMPLETELY ABSORBED IN DOG & MAN. ELIMINATION IS ALSO RAPID & DUE SOLELY TO BIOTRANSFORMATION. /FLURAZEPAM HYDROCHLORIDE/
催眠药，氟拉泽帕姆氢氯酸盐，在狗和人体内已被证明能快速且完全吸收。消除作用也是迅速的，完全由生物转化引起。/氟拉泽帕姆氢氯酸盐/
HYPNOTIC, FLURAZEPAM HYDROCHLORIDE, HAS BEEN SHOWN TO BE RAPIDLY & COMPLETELY ABSORBED IN DOG & MAN. ELIMINATION IS ALSO RAPID & DUE SOLELY TO BIOTRANSFORMATION. /FLURAZEPAM HYDROCHLORIDE/
ORAL ... ((14)CARBON) FLURAZEPAM ... IN DOG & MAN ... ELIMINATED MAINLY IN 3 DAYS. DOG EXCRETED 36 & 49% OF (14)CARBON IN URINE & FECES (PROBABLY VIA BILE) FOLLOWING ORAL DOSE & 27 & 54% FOLLOWING IV DOSE. AFTER ORAL DOSE, HUMANS EXCRETED ... IN FECES (9%) & ... IN URINE (81%). PLASMA (14)CARBON ... PEAKED IN 1 HR FOLLOWING ORAL DOSE IN BOTH SPECIES.
ALL BENZODIAZEPINES BIND TO HUMAN PLASMA ALBUMIN. THE EXTENT OF BINDING VARIES FROM PROBABLY ONLY A FEW PERCENT WITH FLURAZEPAM TO NEARLY 99% WITH DIAZEPAM.
[EN] COMPOUNDS AND THEIR USE AS BACE INHIBITORS<br/>[FR] COMPOSÉS ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE BACE
申请人：ASTRAZENECA AB
公开号：WO2016055858A1
公开（公告）日：2016-04-14
The present application relates to compounds of formula (I), (la), or (lb) and their pharmaceutical compositions/preparations. This application further relates to methods of treating or preventing Αβ-related pathologies such as Down's syndrome, β- amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI ("mild cognitive impairment"), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia, including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease.
New Drug Delivery System for Crossing the Blood Brain Barrier
申请人：Lipshutz H. Bruce
公开号：US20070203080A1
公开（公告）日：2007-08-30
New ubiquinol analogs are disclosed, as well as methods of using these compounds to deliver drug moieties to the body.
新的泛醌类似物被披露，以及利用这些化合物将药物基团输送到人体的方法。
[EN] METHYL OXAZOLE OREXIN RECEPTOR ANTAGONISTS<br/>[FR] MÉTHYLOXAZOLES ANTAGONISTES DU RÉCEPTEUR DE L'OREXINE
申请人：MERCK SHARP & DOHME
公开号：WO2016089721A1
公开（公告）日：2016-06-09
The present invention is directed to methyl oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.
Heterobicyclic compounds of Formula (I):
or a pharmaceutically-acceptable salt, tautomer, or stereoisomer thereof, as defined in the specification, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, Huntington's Disease, and the like.
Formula (I)的杂环化合物：
或其药用可接受的盐、互变异构体或立体异构体，如规范中所定义，并含有它们的组合物，以及制备这种化合物的方法。本文还提供了通过抑制PDE10来治疗由此可治疗的疾病或疾病的方法，如肥胖症、非胰岛素依赖型糖尿病、精神分裂症、躁郁症、强迫症、亨廷顿病等。
[EN] NAPHTHALENE CARBOXAMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] COMPOSÉS DE NAPHTHALÈNE CARBOXAMIDE, MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1
申请人：MERCK SHARP & DOHME
公开号：WO2011149801A1
公开（公告）日：2011-12-01
The present invention is directed to naphthalene carboxamide compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimers disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.
