THERE HAVE BEEN SEVERAL...METABOLIC STUDIES OF TYRAMINE IN MAMMALS, & TRACERS HAVE BEEN USED. ...SMALL AMT OF P-HYDROXYMANDELIC ACID, VANILMANDELIC ACID, & HOMOVANILLIC ACID /HAVE BEEN INDENTIFIED/.
...TYRAMINE...PRESENT IN CHEESE AND IN YEAST EXTRACT...IS NORMALLY DETOXICATED BY MONOAMINE OXIDASE, PRESENT IN INTESTINE AND LIVER, TO YIELD PARA-HYDROXYPHENYLETHANOL, PARA-HYDROXYPHENYLACETIC ACID AND ITS GLYCINE CONJUGATE, PARA-HYDROXYPHENACETURIC ACID, AND...N-ACETYLTYRAMINE.
Tyramine is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.
参考文献:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-批准的药物标签用于研究药物诱导的肝损伤,《药物发现今天》,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: 按照在人类中发展药物诱导肝损伤风险排名的最大参考药物清单。《药物发现今天》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
96% OF (14)C WAS EXCRETED IN 24-HR URINE OF RATS GIVEN IP DOSE OF...(14)C TYRAMINE. 67% WAS EXCRETED IN 3 HR, BUT THIS AMT WAS MARKEDLY REDUCED IF RATS WERE PRETREATED WITH MONOAMINE OXIDASE INHIBITOR. /HUMANS/...EXCRETED 58% OF (14)C IN 24-HR URINE FOLLOWING IV DOSE...
WHEN TYRAMINE...WAS INJECTED INTO RATS, MAJOR URINARY METABOLITE WAS FREE P-HYDROXYPHENYLACETIC ACID...(77% OF THAT PROPORTION OF DOSE EXCRETED IN URINE)...
.../TYRAMINE IS/ POORLY ABSORBED FROM BOWEL, BUT.../IS/ READILY ABSORBED FROM SC INJECTION. .../IT/ MAY BE ABSORBED TO A GREATER OR LESS EXTENT FROM NASAL MUCOSA.
(14)C-LABELED TYRAMINE BOUND TO PLASMA PROTEINS OF RABBITS IN DOSE- & TIME OF INCUBATION-RELATED MANNER. MAX BINDING CAPACITY EST AS 70.2 UG/G. AFFINITY FOR PLASMA PROTEINS MUCH LOWER THAN THAT OF NORADRENALINE.
[EN] THIOPHENE DERIVATIVES FOR THE TREATMENT OF DISORDERS CAUSED BY IGE<br/>[FR] DÉRIVÉS DE THIOPHÈNE POUR LE TRAITEMENT DE TROUBLES PROVOQUÉS PAR IGE
申请人:UCB BIOPHARMA SRL
公开号:WO2019243550A1
公开(公告)日:2019-12-26
Thiophene derivatives of formula (I) and a pharmaceutically acceptable salt thereof are provided. These compounds have utility for the treatment or prevention of disorders caused by IgE, such as allergy, type 1 hypersensitivity or familiar sinus inflammation.
[EN] OXAZOLIDINONE COMPOUNDS AND METHODS OF USE THEREOF AS ANTIBACTERIAL AGENTS<br/>[FR] COMPOSÉS OXAZOLIDINONE ET PROCÉDÉS D'UTILISATION DE CES DERNIERS EN TANT QU'AGENTS ANTIBACTÉRIENS
申请人:MERCK SHARP & DOHME
公开号:WO2017066964A1
公开(公告)日:2017-04-27
The present invention relates to oxazolidinone compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, E, and R1 are as defined herein. The present invention also relates to compositions which comprise at least one oxazolidinone compound of the invention. The invention also provides methods for inhibiting growth of mycobacterial cells as well as a method of treating mycobacterial infections by Mycobacterium tuberculosiscomprising administering a therapeutically effective amount of an oxazolidinone of the invention and/or apharmaceutically acceptable salt thereof, or a composition comprising such compound and/or salt.
Leukotriene A4 hydrolase (LTA4H) inhibitors, compositions containing them, and methods of use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and/or conditions associated with inflammation.
[EN] PHENOTHIAZINE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE PHÉNOTHIAZINE ET LEURS UTILISATIONS
申请人:CAMP4 THERAPEUTICS CORP
公开号:WO2019195789A1
公开(公告)日:2019-10-10
The present invention provides phenothiazine compounds, processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment of various diseases or conditions, for example ribosomal disorders and ribosomopathies, e.g. Diamond Blackfan anemia (DBA).