PARTLY METABOLIZED IN LIVER BY OXIDN OF C-5 SUBSTITUENT(S) (ALLYL &/OR ISOPROPYL GROUPS) ... ALLYL GROUP ... MAY ALSO /BE REMOVED/. RESULTING /IN/ INACTIVE METABOLITES /HUMAN, ORAL/.
来源:Hazardous Substances Data Bank (HSDB)
代谢
肝脏生物转化，主要由肝脏微粒体酶系统进行。/巴比妥类药物/
Hepatic biotransformation, primarily by the hepatic microsomal enzyme system. /barbiturates/
Partially metabolized in the liver by oxidation of the C5 substituent(s) (allyl and/or isopropyl groups). Removal of the allyl group at C5 may also occur. The resulting inactive metbolites, which have not been identified are excreted in the urine.
With the exception of the less lipid-soluble aprobarbital and phenobarbital, nearly complete metabolism and/or conjugation of barbiturates in the liver precedes their renal excretion. The oxidation of radicals at C5 is the most important biotransformation responsible for termination of biological activity. Oxidation results in the formation of alcohols, ketones, phenols, or carboxylic acids, which may appear in the urine as such or as glucuronic acid conjugates. In some instances (eg, phenobarbital), N-glucosylation is an important metabolic pathway. Other biotransformations include N-hydroxylation, desulfuration of thiobarbiturates to oxybarbiturates, opening of the barbituric acid ring, and N-dealkylation of N-alkylbarbiturates to active metabolites (eg, mephobarbital to phenobarbital).
IN CAT CEREBRAL CORTEX, BARBITURATES IN ANESTHETIC DOSES SELECTIVELY ABOLISH EXCITATION BUT NOT INHIBITION ELICITED BY NOREPINEPHRINE APPLIED DIRECTLY TO VARIOUS SYNAPSES... /BARBITURATES/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
相互作用
在骨骼神经肌肉接头处，巴比妥类药物能增强D-筒箭毒碱和十羟季铵的阻断作用。/巴比妥类药物/
AT SKELETAL NEUROMUSCULAR JUNCTIONS BLOCKING EFFECTS OF BOTH D-TUBOCURARINE & DECAMETHONIUM ARE ENHANCED BY BARBITURATES. /BARBITURATES/
TREATMENT: Stabilization: Respiratory arrest is the major cause of early death. Assess the patency of the airway and the adequacy of ventilation first. Appropriate corrective measures include supplemental oxygen, head tilt-chin lift, intubation, and assisted ventilation. Establish an iv line with Ringer's lactate and give a fluid challenge up to 2 l for patients who are hypotensive. Cardiac dysrhythmias are rare but were reported. ... Be sure to give glucose, naloxone, and thiamine to all patients with depressed mental status. /Barbiturates/
RATE OF DECLINE OF BLOOD CONCN AFTER A LARGE DOSE FOR ... ALURATE ... IS 25-40% /PER 24 HR/ ... RATE OF DECLINE IS A FUNCTION OF ACCUMULATION IN LIVER, METAB OF DRUG & URINARY EXCRETION.
AS MUCH AS 50% OF HYPNOTIC DOSE OF ... APROBARBITAL MAY BE EXCRETED UNCHANGED BY KIDNEY. ... APROBARBITAL ... ELIMINATED SLOWLY, OVER A PERIOD OF SEVERAL DAYS.
A FRACTION OF BARBITURATE IN BLOOD IS REVERSIBLY BOUND TO PLASMA PROTEIN, CHIEFLY ALBUMIN. ... THE CEREBROSPINAL FLUID IS VIRTUALLY PROTEIN FREE. ACCORDINGLY, THE MAXIMAL CONCN OF BARBITURATES ATTAINED IN CEREBROSPINAL FLUID IS LESS THAN THE PLASMA CONCN, BEING IN MOST CASES SLIGHTLY LESS THAN THE CONCN IN AN ULTRAFILTRATE OF PLASMA. THE CONCN IN OCULAR FLUID IS SIMILAR TO THAT OF CEREBROSPINAL FLUID. IN TISSUES, THE BARBITURATE CONCN IS GENERALLY AS HIGH AS OR SLIGHTLY HIGHER THAN IN PLASMA. /BARBITURATES/
... SODIUM SALTS ARE MORE RAPIDLY ABSORBED THAN FREE ACIDS ... FOOD IN STOMACH DECR RATE OF ABSORPTION BUT NOT AMT ABSORBED. THERE EXISTS NO IMPENETRABLE BARRIER TO ... BARBITURATES IN BODY ... IF SOJOURN OF DRUG IN PLASMA IS SUFFICIENTLY LONG, IT WILL BE DISTRIBUTED TO ALL TISSUES & FLUIDS. /BARBITURATES/
[EN] S-NITROSOMERCAPTO COMPOUNDS AND RELATED DERIVATIVES<br/>[FR] COMPOSÉS DE S-NITROSOMERCAPTO ET DÉRIVÉS APPARENTÉS
申请人：GALLEON PHARMACEUTICALS INC
公开号：WO2009151744A1
公开（公告）日：2009-12-17
The present invention is directed to mercapto-based and S- nitrosomercapto-based SNO compounds and their derivatives, and their use in treating a lack of normal breathing control, including the treatment of apnea and hypoventilation associated with sleep, obesity, certain medicines and other medical conditions.
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.
PYRROLOPYRAZINE-SPIROCYCLIC PIPERIDINE AMIDES AS MODULATORS OF ION CHANNELS
申请人：Hadida Ruah Sara Sabina
公开号：US20120196869A1
公开（公告）日：2012-08-02
The invention relates to pyrrolopyrazine-spirocyclic piperidine amide compounds useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.
[EN] DEUTERATED PYRIDONE AMIDES AND PRODRUGS THEREOF AS MODULATORS OF SODIUM CHANNELS<br/>[FR] AMIDES DE PYRIDONE DEUTÉRÉS ET LEURS PROMÉDICAMENTS UTILISÉS EN TANT QUE MODULATEURS DE CANAUX SODIQUES
申请人：VERTEX PHARMA
公开号：WO2018213426A1
公开（公告）日：2018-11-22
Compounds, and pharmaceutically acceptable salts thereof, useful as inhibitors of sodium channels are provided. The compounds have the formula (I) wherein R is H or CH2OPO(OH)2. Also provided are pharmaceutical compositions comprising the compounds or pharmaceutically acceptable salts and methods of using the compounds, pharmaceutically acceptable salts, and pharmaceutical compositions in the treatment of various disorders, including pain.
