IDENTIFICATION AND USE: Trigonelline is a solid. Trigonelline, an alkaloid with potential antidiabetic activity, is present in considerable amounts in coffee. It is used in biochemical research. HUMAN EXPOSURE AND TOXICITY: Trigonelline promotes functional neurite outgrowth in human neuroblastoma SK-N-SH cells. ANIMAL STUDIES: Trigonelline showed significant central nervous system (CNS) stimulant activities in rats. Trigonelline differentially affected the skeletal system of rats with streptozotocin-induced metabolic disorders, intensifying the osteoporotic changes in streptozotocin-treated rats and favorably affecting bones in the non-hyperglycemic (nicotinamide/streptozotocin-treated) rats. The results indicate that, in certain conditions, trigonelline may damage bone. In rats, estrogen deficiency caused worsening of bone mineralization and mechanical properties of the tibial metaphysis, as well as increases in bone turnover markers. Administration of trigonelline did not affect the investigated parameters in nonovariectomized rats, but it worsened the mineralization and mechanical properties of cancellous bone in ovariectomized rats. Unfavorable effects of trigonelline on the skeletal system depended on the estrogen status. They were observed only in cancellous bone of estrogen-deficient rats. The results of bacteria mutation assays (Salmonella typhimurium strains TA98, YG1024 and YG1029) showed that trigonelline, alone or in combination with most of the single amino acids and mixtures of amino acids, yielded potent mutagenic activity. However, in another study it was found not mutagenic in the Salmonella plate incorporation assay and mouse lymphoma L5178Y TK +/- assay.
The effects of both coffee components and coffee extract on the electrical responses of GABA(A) receptors expressed in Xenopus oocytes were studied by injecting cRNAs of the alpha(1) and beta(1) subunits of the bovine receptors. The aqueous extract of coffee dose-dependently inhibited the GABA-elicited responses, whereas the lipophilic extract of coffee by diethyl ether slightly potentiated it at low doses (0.1-0.4 uL/mL) but showed inhibition at high doses (0.5-0.8 uL/mL). Theophylline inhibited the response in a noncompetitive mechanism (K(i) = 0.55 mM), whereas theobromine and trigonelline hydrochloride inhibited it in a competitive manner, K(i) = 3.8 and 13 mM, respectively... /Trigonelline hydrochloride/
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
解毒与急救
/SRP:/ 高级治疗：对于昏迷、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用带气囊的面罩进行正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W TKO /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸钠林格氏液（LR）。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。/毒物A和B/
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
... The concentration-time curves of trigonelline in rabbits after ... iv administration were shown to fit one-compartment and two-compartment open model, respectively. The main parameters after iv /administration/ of trigonelline were as follows: T1/2 alpha was 10.8 min, T1/2 beta was 44.0 min, K21 was 0.044 min-1, K10 was 0.026 min-1, K12 was 0.017 min-1, AUC was 931.0 mg.min/L . /It was concluded that/ trigonelline showed a middle rate of absorption and fast rate of elimination in rabbit...
Cerebral function enhancers: acyclic amide derivatives of
申请人：Bristol-Myers Squibb Company
公开号：US05338738A1
公开（公告）日：1994-08-16
A series of acyclic amide derivatives of pyrimidinylpiperazines of Formula I ##STR1## wherein R.sup.1 is alkyl, phenalkyl, phenyl-hydroxyalkyl, phenyl and pyridinyl; R.sup.2 and R.sup.3 are hydrogen and alkyl; and R.sup.4 is hydrogen, halogen, and trifluoromethyl. Compounds of the invention can be incorporated into pharmaceutical compositions for use in enhancing cerebral function. The compounds are envisioned as being useful in restoration of cerebral function in degenerative disorders; in amnesia reversal; and in improvement of memory and learning processes.
The present invention relates to novel therapeutic dendrimer conjugates configured for the treatment and/or prevention of organophosphate poisoning. In particular, the present invention is directed to dendrimers complexed with organophosphate poisoning antidotes (e.g., pralidoxime (2-PAM) (4-PAM), obidoxime, trimedoxime, asoxime (HI-6), hydroxamate, and related analogs, salts and derivatives thereof), compositions comprising such dendrimer conjugates, related methods of synthesizing such dendrimer conjugates, as well as systems and methods utilizing such dendrimer conjugates (e.g., in diagnostic and/or therapeutic settings (e.g., for the delivery of therapeutics, imaging, and/or targeting agents (e.g., in the treatment and/or prevention of organophosphate poisoning)).
[EN] SMALL MOLECULE INDUCERS OF REACTIVE OXYGEN SPECIES AND INHIBITORS OF MITOCHONDRIAL ACTIVITY<br/>[FR] INDUCTEURS DE PETITES MOLÉCULES DE DÉRIVES RÉACTIFS DE L'OXYGÈNE ET INHIBITEURS DE L'ACTIVITÉ MITOCHONDRIALE
申请人：UNIV MICHIGAN REGENTS
公开号：WO2017155991A1
公开（公告）日：2017-09-14
This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a quinazolinedione structure which function as reactive oxygen species (ROS) inducers and inhibitors of mitochondrial activity within cancer cells (e.g., pancreatic cancer cells), and their use as therapeutics for the treatment of cancer (e.g., pancreatic cancer) and other diseases.
[EN] COMPOSITIONS COMPRISING LIPOPHILIC DIESTERS OF CHELATING AGENTS NON-COVALENTLY ASSOCIATED WITH ORGANIC AMINES<br/>[FR] COMPOSITIONS COMPRENANT DES DIESTERS LIPOPHILES D'AGENTS CHÉLATANTS EN ASSOCIATION NON COVALENTE AVEC DES AMINES ORGANIQUES
申请人：DPHARM LTD
公开号：WO2015092788A1
公开（公告）日：2015-06-25
The present invention provides pharmaceutical compositions comprising lipophilic diesters of l,2-bis(2-aminophenoxy)ethane-N,N,N',N' -tetraacetic acid denoted herein as B APTA-DE, or salts thereof, in non-covalent association with a free amino acid, wherein a stoichiometric ratio of the free amino acid and the lipophilic diester in the composition is at least 3: 1, M denotes a hydrogen ion and/or a physiologically acceptable cation, and wherein R is selected from the group consisting of CnH2n+1 (n=1-10), CnH2n+1(OCH2CH2)m (n=1-20, m=1-6), (CnH2n+1)2N(CH2)m (n=1-6, m=1-6) and substituted or unsubstituted ArCH2; the substituents on the aromatic rings being in the ortho position. The invention further concerns use of said pharmaceutical compositions in the treatment of neurological conditions or diseases related to abnormal levels of divalent metal ions, said treatment resulting in minimizing the risk of developing undesired side effects associated with the therapeutic use of the lipophilic diester salts.
本发明提供了包含疏水性二酯化合物 l,2-双(2-氨基苯氧基)乙烷-N,N,N',N' -四乙酸（在此称为 B APTA-DE）或其盐的药物组合物，与游离氨基酸非共价结合，其中组合物中游离氨基酸和疏水性二酯之间的化学计量比至少为 3:1，M 代表氢离子和/或生理上可接受的阳离子，R 选自由 CnH2n+1（n=1-10）、CnH2n+1(O )m（n=1-20，m=1-6）、(CnH2n+1)2N(CH2)m（n=1-6，m=1-6）和取代或未取代的 Ar 组成的基团；芳香环上的取代基位于邻位。该发明还涉及上述药物组合物在治疗与二价金属离子异常水平相关的神经病症或疾病中的应用，该治疗有助于减少与疏水性二酯盐的治疗应用相关的不良副作用的风险。
