It is metabolized in the liver by mescaline oxidase into numerous inactive metabolites. These include 3,4,5-trimethoxyphenylacetic acid; 3,4,5-trimethoxybenzoic acid; 3,4-dihydroxy-5-methoxy-phenyl-lacetyl glutamine; 3-hydroxy-4,5-dimethoxyphenylethylamine; N-acetylmescaline; and N-acetyl-3,4-dimethoxy-5-hydroxyphenylethylamine.
来源:Hazardous Substances Data Bank (HSDB)
代谢
一些兔组织体外代谢麦斯卡林的情况被研究了。肺匀浆的麦斯卡林氧化活性（微摩尔/每毫克蛋白/15分钟）是肝脏或肾脏的四倍。大脑和血浆对麦斯卡林的代谢能力相对较低。体外麦斯卡林代谢对半碳酰胺的抑制敏感。从灌注隔离兔肺的介质中移除麦斯卡林可以通过肺内代谢来解释。半碳酰胺（10(-3) M 苄胍）处理的肺比未处理的肺积累更多的麦斯卡林。肺对麦斯卡林的排出速度比其代谢物慢。这些结果表明，完整的肺移除了灌注的麦斯卡林，可能在体内循环麦斯卡林的处置中发挥重要作用。
Metabolism of mescaline by several rabbit tissues was examined in vitro. Mescaline-oxidizing activity (micromoles/ per milligram of protein/15 min) of lung homogenates was 4 times greater than that of either liver or kidney. Brain and plasma each had comparatively little capacity to metabolize mescaline. Mescaline metabolism in vitro was sensitive to inhibition by semicarbazide. Removal of mescaline from the medium perfusing the isolated rabbit lung was explained by intrapulmonary metabolism. Semicarbazide (10(-3) M pargyline. Semicarbazide-treated lungs accumulated more mescaline than did untreated lungs. Mescaline efflux from lung was slower than that of its metabolite. These results indicate that the intact lung removes perfused mescaline and may be important in the disposition of circulating mescaline in vivo.
Mescaline (25 mg/kg; 66 muc/kg) was injected (ip) in mice 45 min before chlorpromazine (2.5, 5, 15 mg/kg), thioridazine (10, 30, 45 mg/kg), or chlorpromazine-sulfoxide (15 mg/kg). Excitement, agitation, slight increase in ventilation and occasional head-shaking were seen 30 min after mescaline and continued for 30-45 min thereafter; locomotor activity and the number of scratching events were significantly increased during this period. chlorpromazine (2.5, 5, 15 mg/kg) and thioridazine (10, 30, 45 mg/kg) partially or completely blocked mescaline-induced gross behavior; chlorpromazine-sulfoxide (15 mg/kg) was not effective. Increased scratching responses and locomotor activity induced by mescaline were antagonized by all doses of chlorpromazine and thioridazine; at higher doses, both chlorpromazine (7.5, 15 mg/kg) and thioridazine (45 mg/kg) induced cataleptic-like condition and marked hypothermia. Tissue levels of mescaline, examined 3 hr after its administration, were increased by all doses of chlorpromazine and a higher dose of thioridazine (45 mg/kg); chlorpromazine-sulfoxide and lower doses of thioridazine had no effect.
For patient with a "bad trip" or panic reaction, provide gentle reassurance and relaxation techniques in a quiet environment. Treat agitation or severe anxiety states with diazepam or midazolam. Butyrophenones such as haloperidol are useful despite a small theoretic risk of lowering seizure threshold. Treat seizures, hyperthermia, rhabdomyolysis, hypertension, and cardiac arrhythmias if they occur. /LSD and other hallucinogens/
Specific Drugs and Antidotes: There are no specific antidote. Sedating doses of diazepam may alleviate anxiety, and hypnotic doses can induce sleep for the duration of the "trip". /LSD and other hallucinogens/
Decontamination: Most of these drugs are taken orally in small doses, and decontamination procedures are relatively ineffective and likely to aggravate psychological distress. Consider the use of activated charcoal ... only after recent (within 30-60 minutes) large ingestions. /LSD and other hallucinogens/
Enhanced Elimination: These procedures are not useful. Although urinary acidification may increase the urine concentrations of some agents, it does not significantly enhance total-body elimination and may aggravate myoglobinuric renal failure. /LSD and other hallucinogens/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
Mescaline binds to liver proteins but not to plasma proteins. It is rapidly and widely distributed into the peripheral tissues. The volume of distribution is not specifically known but is believed to be on the order of several L/kg.
美斯卡林与肝脏蛋白结合，但与血浆蛋白不结合。它迅速且广泛地分布到周围组织中。分布容积的具体数值尚不清楚，但据信在几升/公斤的量级。
Mescaline binds to liver proteins but not to plasma proteins. It is rapidly and widely distributed into the peripheral tissues. The volume of distribution is not specifically known but is believed to be on the order of several L/kg.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
60%的致幻剂在24小时内以原形排出体外，其余的以代谢物形式排出。
Sixty percent of mescaline is excreted unchanged in a 24 hour urine, and the rest is excreted as metabolites.
Peyote is rapidly absorbed after ingestion. The onset of action is between 30 minutes and 2 hours, and peak blood levels occur 2 hours after ingestion. The duration of the effect usually ranges from 6 to 12 hours but may last up to 14 hours. /Peyote/
Rats of 1, 4, 8, 12, 20, and 60 days postnatal age were injected ip with (14)C-mescaline (50 nCi/g). The levels of mescaline and its deaminated metabolite, 3,4,5-trimethoxyphenylacetic acid, were examined in the brain, liver, heart, spleen, lung, and kidney at 30, 60, 90, and 120 min. Mescaline was rapidly taken up by all the organs examined. In general, the organs of younger rats accumulated much larger amounts than those of adult animals. Brain concentrated the lowest amounts in comparison with other tissues. In the brain, the uptake was the highest in 1-day-old rats and decreased with age. The disappearance of mescaline in various organs was comparatively slower in younger animals than in 20-day or older rats. Rats immediately after birth and uptake was the highest in 1-day-old rats and decreased with age. The disappearance of mescaline in various organs was comparatively slower in younger animals than in 20-day or older rats. Rats immediately after birth and up to 20 days of age metabolized mescaline less efficiently than adults. From the data, it appears that the blood-brain barrier for mescaline develops gradually with age but is not completely impermeable in adults.
[EN] 5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE<br/>[FR] AGONISTES DE RÉCEPTEUR 5-HT2C ET COMPOSITIONS ET PROCÉDÉS D'UTILISATION
申请人：ARENA PHARM INC
公开号：WO2017023679A1
公开（公告）日：2017-02-09
Provided in some embodiments are compounds of Formula A, as defined herein, that modulate the activity of 5-HT2C receptor. Also provided in some embodiments are methods, such as, for weight management, inducing satiety, and decreasing food intake, and for preventing and treating obesity, antipsychotic-induced weight gain, type 2 diabetes, Prader-Willi syndrome, tobacco/nicotine dependence, drug addiction, alcohol addiction, pathological gambling, reward deficiency syndrome, and sex addiction), obsessive-compulsive spectrum disorders and impulse control disorders (including nail-biting and onychophagia), sleep disorders (including insomnia, fragmented sleep architecture, and disturbances of slow-wave sleep), urinary incontinence, psychiatric disorders (including schizophrenia, anorexia nervosa, and bulimia nervosa), Alzheimer disease, sexual dysfunction, erectile dysfunction, epilepsy, movement disorders (including parkinsonism and antipsychotic-induced movement disorder), hypertension, dyslipidemia, nonalcoholic fatty liver disease, obesity-related renal disease, and sleep apnea.
SUGAR CHAIN-ATTACHED LINKER, COMPOUND CONTAINING SUGAR CHAIN-ATTACHED LINKER AND PHYSIOLOGICALLY ACTIVE SUBSTANCE OR SALT THEREOF, AND METHOD FOR PRODUCING SAME
申请人：GLYTECH INC.
公开号：US20150306235A1
公开（公告）日：2015-10-29
To provide a carrier linker that is capable of improving the water solubility of a physiologically active substance and more quickly releasing the physiologically active substance under specific conditions without utilizing light or enzymatic cleavage.
[Solution]A novel sugar chain-attached linker comprising a sugar chain that is attached as a carrier.
CONJUGATE-BASED ANTIFUNGAL AND ANTIBACTERIAL PRODRUGS
申请人：Bapat Abhijit S.
公开号：US20140364595A1
公开（公告）日：2014-12-11
The invention provides conjugate-based antifungal or antibacterial prodrugs formed by coupling at least one anti-fungal agent or antibacterial agent with at least one linker and/or carrier. The prodrugs are of formula: (i) (AFA)
m
-X-(L)
n
; (ii) [(AFA)
m′
-X]
p
-L; (iii) AFA-[X-(L)
n′
]
q
; or (iv) (AFA)
m″
-X, wherein: AFA is an antifungal agent or an antibacterial agent; L is a carrier; X is a linker; m ranges from 1 to 10; n ranges from 2 to 10; m′ is 1 to 10; p is 1 to 10; n′ is 1 to 10; and q is 1 to 10, provided that q′ and n are not both 1; and m″ is 1 to 10. The invention also provides nanoparticles comprising the conjugate-based prodrugs. Additionally, the invention also provides non-conjugated antifungal and antibacterial agents in the form of nanoparticles.
该发明提供了由至少一种抗真菌剂或抗菌剂与至少一种连接剂和/或载体偶联形成的基于共轭的抗真菌或抗菌前药。这些前药的公式为：(i) (AFA)
m
-X-(L)
n
; (ii) [(AFA)
m′
-X]
p
-L; (iii) AFA-[X-(L)
n′
]
q
; 或 (iv) (AFA)
m″
-X，其中：AFA是抗真菌剂或抗菌剂；L是载体；X是连接剂；m范围从1到10；n范围从2到10；m′为1到10；p为1到10；n′为1到10；q为1到10，前提是q'和n不同时为1；m″为1到10。该发明还提供了包含基于共轭的前药的纳米粒子。此外，该发明还提供了以纳米粒子形式的非共轭抗真菌和抗菌剂。
Structure–activity relationship and biological evaluation of berberine derivatives as PCSK9 down-regulating agents
deficiency markedly enhanced the survival rate of patient with cardiovascular diseases (CVDs). Forty berberine (BBR) derivatives were synthesized and evaluated for their activities on down-regulating the transcription of PCSK9 in HepG2 cells, taking BBR as the lead. Structure–activityrelationship (SAR) analysis revealed that 2,3-dimethoxy moiety might be beneficial for activity. Among them, 9k displayed the
[EN] NOVEL INDOLE AND PYRROLOPYRIDINE AMIDES<br/>[FR] NOUVEAUX AMIDES D'INDOLE ET DE PYRROLOPYRIDINE
申请人：ACTELION PHARMACEUTICALS LTD
公开号：WO2012114252A1
公开（公告）日：2012-08-30
The present invention relates to indole and pyrrolopyridine amide derivatives of formula (I) wherein R1, R 2, R 3, U, V, W, X, Y, Z and ring A are as described in the description, to their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), and especially to their use as orexin receptor antagonists.
