Sol in 9.5 parts water at 15 °C; freely sol in alcohol, ether, chloroform, acetone; sparingly sol in benzene, petroleum ether
蒸汽压力：
7.18X10-9 mm Hg at 25 °C (est)
稳定性/保质期：
The commercially available transdermal system of scopolamine should be stored at controlled room temperature between 20 and 25 °C. Scopolamine hydrobromide should be stored in tight, light-resistant containers. Scopolamine hydrobromide injections should be stored in light-resistant, single-dose or multiple-dose containers, preferably of USP Type I glass, at 15 to 30 °C; freezing of the injections should be avoided. Commercially available scopolamine hydrobromide soluble tablets should be stored at controlled room temperature (15 to 30 °C).
旋光度：
Specific optical rotation: -28 deg at 20 °C/D ( c = 2.7)
Although the metabolic and excretory fate of scopolamine has not been fully determined, the drug is thought to be almost completely metabolized (principally by conjugation) in the liver and excreted in urine.
来源:Hazardous Substances Data Bank (HSDB)
代谢
消除途径：在108小时内，总剂量的不到10%以原形和代谢物形式通过尿液排出。
半衰期：4.5小时
Route of Elimination: Less than 10% of the total dose is excreted in the urine as parent and metabolites over 108 hours.
Half Life: 4.5 hours
来源:Toxin and Toxin Target Database (T3DB)
毒理性
毒性总结
东莨菪碱通过干扰副交感神经系统（特别是呕吐中枢）中乙酰胆碱传递神经冲动的作用。
Scopolamine acts by interfering with the transmission of nerve impulses by acetylcholine in the parasympathetic nervous system (specifically the vomiting center).
参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 美国食品药品监督管理局批准的药物标签用于研究药物诱导的肝损伤，《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：按人类发展药物诱导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
Scopolamine hydrobromide is rapidly absorbed following IM or subcutaneous injection. The drug is well absorbed from the GI tract, principally from the upper small intestine. Scopolamine also is well absorbed percutaneously. Following topical application behind the ear of a transdermal system, scopolamine is detected in plasma within 4 hours, with peak concentrations occurring within an average of 24 hours. In one study in healthy individuals, mean free and total (free plus conjugated) plasma scopolamine concentrations of 87 and 354 pg/mL, respectively, have been reported within 24 hours following topical application of a single transdermal scopolamine system that delivered approximately 1 mg/72 hours. /Scopolamine hydrobromide/
Following oral administration of a 0.906-mg dose of scopolamine in one individual, a peak concentration of about 2 ng/mL was reached within 1 hour. Although the commercially available transdermal system contains 1.5 mg of scopolamine, the membrane-controlled diffusion system is designed to deliver approximately 1 mg of the drug to systemic circulation at an approximately constant rate over a 72-hour period. An initial priming dose of 0.14 mg of scopolamine is released from the adhesive layer of the system at a controlled, asymptotically declining rate over 6 hours; then, the remainder of the dose is released at an approximate rate of 5 ug/hour for the remaining 66-hour functional lifetime of the system. The manufacturer states that the initial priming dose saturates binding sites on the skin and rapidly brings the plasma concentration to steady-state. In a crossover study comparing urinary excretion rates of scopolamine during multiple 12-hour collection intervals in healthy individuals, there was no difference between the rates of excretion of drug during steady-state (24-72 hours) for constant-rate IV infusion (3.7-6 mcg/hour) and transdermal administration. The transdermal system appeared to deliver the drug to systemic circulation at the same rate as the constant-rate IV infusion; however, relatively long collection intervals (12 hours) make it difficult to interpret the data precisely. During the 12- to 24-hour period of administration and after 72 hours, the rate of excretion of scopolamine was higher with the transdermal system than with the constant-rate IV infusion.
The distribution of scopolamine has not been fully characterized. The drug appears to be reversibly bound to plasma proteins. Scopolamine apparently crosses the blood-brain barrier since the drug causes CNS effects. The drug also reportedly crosses the placenta and is distributed into milk..
Although the metabolic and excretory fate of scopolamine has not been fully determined, the drug is thought to be almost completely metabolized (principally by conjugation) in the liver and excreted in urine. Following oral administration of a single dose of scopolamine in one study, only small amounts of the dose (about 4-5%) were excreted unchanged in urine within 50 hours; urinary clearance of unchanged drug was about 120 mL/minute. In another study, 3.4% or less than 1% of a single dose was excreted unchanged in urine within 72 hours following subcutaneous injection or oral administration of the drug, respectively. Following application of a single transdermal scopolamine system that delivered approximately 1 mg/72 hours in healthy individuals, the urinary excretion rate of free and total (free plus conjugated) scopolamine was about 0.7 and 3.8 ug/hour, respectively. Following removal of the transdermal system of scopolamine, depletion of scopolamine bound to skin receptors at the site of the application of the transdermal system results in a log-linear decrease in plasma scopolamine concentrations. Less than 10% of the total dose is excreted in urine as unchanged drug and its metabolites over 108 hours.
[EN] BENZAMIDE OR BENZAMINE COMPOUNDS USEFUL AS ANTICANCER AGENTS FOR THE TREATMENT OF HUMAN CANCERS<br/>[FR] COMPOSÉS BENZAMIDE OU BENZAMINE À UTILISER EN TANT QU'ANTICANCÉREUX POUR LE TRAITEMENT DE CANCERS HUMAINS
申请人：UNIV TEXAS
公开号：WO2017007634A1
公开（公告）日：2017-01-12
The described invention provides small molecule anti-cancer compounds for treating tumors that respond to cholesterol biosynthesis inhibition. The compounds selectively inhibit the cholesterol biosynthetic pathway in tumor-derived cancer cells, but do not affect normally dividing cells.
[EN] SUBSTITUTED N-HETEROCYCLIC CARBOXAMIDES AS ACID CERAMIDASE INHIBITORS AND THEIR USE AS MEDICAMENTS<br/>[FR] CARBOXAMIDES N-HÉTÉROCYCLIQUES SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS DE LA CÉRAMIDASE ACIDE ET LEUR UTILISATION EN TANT QUE MÉDICAMENTS
申请人：BIAL BIOTECH INVEST INC
公开号：WO2021055627A1
公开（公告）日：2021-03-25
The invention provides substituted N-heterocyclic carboxamides and related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat a medical disorder, e.g., cancer, lysosomal storage disorder, neurodegenerative disorder, inflammatory disorder, in a patient.
The present invention relates compounds of the formula: or pharmaceutically acceptable salts thereof, useful as sodium channel blockers, as well as compositions containing the same, processes for the preparation of the same, and therapeutic methods of use therefore in promoting hydration of mucosal surfaces and the treatment of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, bronchiectasis, acute and chronic bronchitis, emphysema, and pneumonia.
CHLORO-PYRAZINE CARBOXAMIDE DERIVATIVES WITH EPITHELIAL SODIUM CHANNEL BLOCKING ACTIVITY
申请人：Parion Sciences, Inc.
公开号：US20140171447A1
公开（公告）日：2014-06-19
This invention provides compounds of the formula I:
and their pharmaceutically acceptable salts, useful as sodium channel blockers, compositions containing the same, therapeutic methods and uses for the same and processes for preparing the same.
The present invention is directed to novel compounds of Formula (I) and pharmaceutically acceptable salts thereof,
pharmaceutical compositions and their use as dual chromaphores having inhibitory activity against PDE4 and muscarinic acetylcholine receptors (mAChRs), and thus being useful for treating respiratory diseases.
