Approximately 80% of body calcium is excreted in the feces as insoluble salts; urinary excretion accounts for the remaining 20%.
来源:DrugBank
毒理性
副作用
Dermatotoxin - 皮肤烧伤。
Dermatotoxin - Skin burns.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
毒理性
相互作用
在Sesamum indicum cv. PB-1的早期生长阶段，与同水平的Pb2+和Cu2+相比，1.0 mM Cd2+处理下，鲜重和干重的减少更为显著。当向生长中的幼苗提供10.0 mM（1.9 EC）氯化钙，并与各种金属盐组合使用时，可以从金属胁迫中显著恢复根的鲜重，几乎完全恢复根的干重。在没有或存在10.0 mM氯化钙的情况下，二价Pb、Cd和Cu的积累对于金属和植物部位是不同的。内源金属积累的顺序是Cu > Cd > Pb，无论是否提供氯化钙，根部的金属积累量都高于叶片。氯化钙可以恢复由任何金属组合引起的根中活体NRA的损失，而当叶子中的NRA损失仅由Pb---Cd（每种1.0 mM）引起时，该盐可以恢复。另一方面，当使用体外分析测试方法直接测定酶时，根和叶的NRA反应是不同的，盐极大地加速了酶活性的损失。然而，仅用氯化钙和以各种组合提供的金属，根和叶的有机氮含量显著增加（p < 0.001）。数据表明，在根环境中存在10.0 mM氯化钙的情况下，尽管根部和叶部积累了大量的二价Cu、Cd和Pb，但金属毒性在很大程度上得到了恢复，这涉及到幼苗的根和叶的生长和硝酸盐还原。
In the early growth phase of Sesamum indicum cv. PB-1, the decrease in fresh and dry mass was higher with 1.0 mM Cd2+ than with the same level of Pb2+ and Cu2+. Recovery from the metal stress was considerable in the root fresh weight and almost completely in the root dry weight when 10.0 mM (1.9 EC), calcium chloride was supplied to the growing seedlings along with the metal salts in various combinations. Accumulation of /divalent/ Pb, Cd and Cu was differential to the metals and the plant parts when supplied without or with 10.0 mM calcium chloride. The order of endogenous metal accumulation was Cu Cd Pb and roots accumulated more metal than the leaves in the absence, as well as in the presence, of calcium chloride. Calcium chloride could recover loss of in vivo NRA in roots caused by either of the metal combinations, whereas the salt could recover the loss in leaf NRA caused only by Pb---Cd (1.0 mM each). Response of root and leaf NRA was on the other hand, different when the enzyme was assayed directly using an in vitro assay method, and the salt accelerated the loss in enzyme activity drastically. The organic-N content of root and leaf was, however, increased significantly (p < 0.001) with calcium chloride alone and with the metals supplied in various combinations. /The/ data indicate that instead of a high endogenous accumulation of /divalent/ Cu, Cd and Pb in roots and leaves the metal toxicity is recovered to a great extent in the presence of 10.0 mM calcium chloride in the root environment regarding growth and nitrate reduction of the roots and leaves of young sesame seedlings.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
相互作用
地尔硫卓通常用于治疗伴有快速心室反应的心房颤动或扑动（AFF）。尽管它在控制心率方面非常有效，但据报道，地尔硫卓引起的低血压（定义为收缩压（SBP）< 90 mm Hg）的患病率高达18%，从超过450名患者的研究中报告的平均低血压发生率为9.7%。这种低血压可能会使治疗复杂化。本研究的目的是确定氯化钙（CaCl2）预处理是否能够减弱静脉注射地尔硫卓后的SBP下降，同时保持地尔硫卓的有效性。进行了一项前瞻性、随机、双盲、安慰剂对照研究。共纳入78名心房颤动且心室率大于或等于120次/分钟的患者。一半接受了静脉注射CaCl2预处理；另一半接受了安慰剂。然后所有患者接受标准、基于体重的静脉注射地尔硫卓。如果临床上需要额外的速率控制，则根据指示给予第二剂CaCl2预处理或安慰剂和地尔硫卓。CaCl2和安慰剂预处理组的心率降低程度相同（p < 0.001）。钙预处理研究组中没有不良事件。安慰剂组中有1名患者在注射地尔硫卓后心率反常地加快并且出现呼吸暂停。尽管静脉注射CaCl2与安慰剂作为预处理相比在治疗伴有RVR的AFF方面似乎同样安全，但研究者们未能发现CaCl2静脉预处理对SBP下降有统计学意义上的显著抑制作用。
Diltiazem is commonly used to treat atrial fibrillation or flutter (AFF) with rapid ventricular response (RVR). Although it is very effective for rate control, up to an 18% prevalence of reported diltiazem-induced hypotension (defined by systolic blood pressure (SBP) < 90 mm Hg), and a mean of 9.7% hypotension have been reported from several studies totaling over 450 patients. This hypotension may complicate therapy. /This study/ objective was to determine if calcium chloride (CaCl2) pre-treatment would blunt a SBP drop after i.v. diltiazem, while allowing diltiazem to maintain its efficacy. A prospective, randomized, double-blind, placebo-controlled study was conducted. Seventy-eight patients with AFF and a ventricular rate of > or = 120 beats per minute were enrolled. Half received i.v. CaCl2 pre-treatment; the other half received placebo. All patients then received i.v. diltiazem in a standard, weight-based dose. A second dose of CaCl2 pre-treatment or placebo and diltiazem was given if clinically indicated for additional rate control. Both CaCl2 and placebo pre-treatment groups had equal lowering of heart rate (p < 0.001). There were no adverse events in the calcium pre-treatment study arm. One patient in the placebo group became paradoxically more tachycardic and apneic after the diltiazem infusion. Although i.v. CaCl2 seems to be equally safe compared to placebo as a pre-treatment in the management of AFF with RVR, /the researchers/ were unable to find a statistically significant blunting of SBP drop with CaCl2 i.v. pre-treatment.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
相互作用
长春花（Catharanthus roseus (L.) G. Don）植株在含有NaCl和CaCl2的条件下生长，以研究CaCl2对NaCl诱导的氧化应激的影响，具体包括脂质过氧化（TBARS含量）、H2O2含量、渗透调节物质浓度、脯氨酸（PRO）代谢酶、抗氧化酶活性以及吲哚生物碱积累。植株分别用80 mM NaCl、80 mM NaCl加5 mM CaCl2和单独5 mM CaCl2的溶液处理。对照组植物使用地下水灌溉。播种后90天（DAS）随机拔除植株。与对照组相比，NaCl处理的植株显示出TBARS、H2O2、甘氨酸甜菜碱（GB）和PRO含量的增加，PROX（脯氨酸氧化酶）活性降低，以及gamma-谷氨酰激酶（gamma-GK）活性的增加。向NaCl处理的植株中添加CaCl2，通过提高PROX水平和降低gamma-GK活性，降低了PRO的浓度。钙离子增加了GB的含量。CaCl2似乎通过在GB积累中与NaCl的叠加作用，提供了更大的渗透保护。在盐分条件下，超氧化物歧化酶（SOD）、过氧化物酶（POX）和过氧化氢酶（CAT）的抗氧化酶活性增加，并且由于CaCl2的处理而进一步增强。与仅NaCl处理和无处理的植株相比，NaCl加CaCl2处理的C. roseus植株在茎和根中的总吲哚生物碱含量有所增加。
Catharanthus roseus (L.) G. Don. plants were grown with NaCl and CaCl2 in order to study the effect of CaCl2 on NaCl-induced oxidative stress in terms of lipid peroxidation (TBARS content), H2O2 content, osmolyte concentration, proline (PRO)-metabolizing enzymes, antioxidant enzyme activities, and indole alkaloid accumulation. The plants were treated with solutions of 80 mM NaCl, 80 mM NaCl with 5 mM CaCl2 and 5 mM CaCl2 alone. Groundwater was used for irrigation of control plants. Plants were uprooted randomly on 90 days after sowing (DAS). NaCl-stressed plants showed increased TBARS, H2O2, glycine betaine (GB) and PRO contents, decreased proline oxidase (PROX) activity, and increased gamma-glutamyl kinase (gamma-GK) activity when compared to control. Addition of CaCl2 to NaCl-stressed plants lowered the PRO concentration by increasing the level of PROX and decreasing the gamma-GK activities. Calcium ions increased the GB contents. CaCl2 appears to confer greater osmoprotection by the additive role with NaCl in GB accumulation. The antioxidant enzymes superoxide dismutase (SOD), peroxidase (POX) and catalase (CAT) were increased under salinity and further enhanced due to CaCl2 treatment. The NaCl-with-CaCl2-treated C. roseus plants showed an increase in total indole alkaloid content in shoots and roots when compared to NaCl-treated and untreated plants.
/This study was conducted/ to evaluate the hemodynamic effects of calcium chloride in a canine model of acute propranolol toxicity. Two minutes after the completion of a propranolol infusion (10 mg/kg), a bolus of 0.125 mL/kg 10% CaCl solution followed by an infusion of 0.375 mL/kg over the next 30 minutes or a bolus and subsequent infusion of an equivalent volume of normal saline solution was administered to each dog. CaCl yielded significant improvements in propranolol-induced decreases in cardiac index and stroke volume compared with saline solution-treated control animals (overall alpha = 0.05). Furthermore, CaCl administration resulted in earlier improvement in propranolol-induced alterations in mean arterial pressure, maximal left ventricular pressure change over time, and peripheral vascular resistance compared with saline solution (overall alpha = 0.05). We observed no difference between treatment groups in response to propranolol-induced bradycardia or QRS-interval prolongation. In this model of acute propranolol toxicity, CaCl therapy improved depressed hemodynamic status, mainly by a positive inotropic action.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
消除途径
大约80%的体内钙以不溶性盐的形式通过粪便排出；其余20%通过尿液排出。
Approximately 80% of body calcium is excreted in the feces as insoluble salts; urinary excretion accounts for the remaining 20%.
A rat placenta was dually perfused in situ with modified Krebs fluid. Perfusion was carried out through the femoral artery on the maternal side and through the umbilical artery on the fetal side. Transfer of 45Ca2+ and 3(H)L-glucose across the placenta was measured in the maternal-fetal direction. The transcellular component of the maternal-fetal transport of Ca2+, Jmf,tc, was estimated from transfer rates of the two tracers and from Ca2+ concentration in maternal perfusate, [Ca2+]m. At [Ca2+]m of l.l mM (physiological concentration of Ca2+ in plasma) Jmf,tc was 92.4 + or - 13.7 nM min-l (mean + or - SD), which is about 90% of the transport expected in an intact placenta. The permeability-surface area product (PS) of the placenta to 3(H)L-glucose was 13.8 + or - 3.9 uL min-l, about 4 times higher than that expected in intact placenta. Transport of 45Ca2+ chanced rapidly when [Ca2+]m was varied. Kinetic constants of the transcellular transport of Ca2+ are the Michaelis constant~ Km, = 0.45 mM and the maximum rate of transport, Vmax, = 116 nM min-l. It follows from this that at physiological levels of Ca2+, transport of Ca2+ to the fetus is relatively independent of changes in [Ca2+]m. Strontium and barium (SrCl2 and BaC12, l mM) decreased Jmf,tc; the response was prompt and reversible. Magnesium (2 mM) had no effect. Maternal-fetal transport of 85Sr2+ and 133Ba2+ was decreased rapidly and reversibly by elevating [Ca2+]m from 0.35 to 2 mM. These observations suggest that Sr2+ and Ba2+ are transported across tile placenta by the Ca2+ transport system. This means that the transport is not substrate specific. Cadrium (1 mM-CdCl2) decreased Jmf,tc irreversibly with some latency. The slowness of the response suggests a non-competitive inhibition. Cadmium (0.02 mM-CdCl2) was without effect on Jmf,tc. 7. A Ca2+ channel blocker, nifedipine (10 uM), administered to the maternal side had no effect on Jmf,tc. /calcium salts/
The paracellular and trancellular components of Ca+2 transfer across the perfused human placental cotyledon was dissected and the nature of the transcellular component was explored. Transfer of 45 Ca+2 and ethylenediaminetetraacetic acid labeled with chromiun (51)CR was measured across the in vitro perfused cotyledon of the human placenta and paracellular and transcellular components of the transfer of Ca+2 were calculated from the transfer of the two tracers. The transcellular component of the Ca+2 transfer in the maternal-fetal direction represented about one third of the total maternal-fetal transfer. It was saturable sensitive to cyanide and insensitive to verapamil. The transcellular component in the fetal-maternal direction was not different from zero. The in vitro transfer rates correlated well with the transfer rates estimated for the in vivo situation from data published in the literature. There is a significant active transport of Ca+2 across the human placenta in the maternal-fetal direction. /calcium salts/
申请人：Agro-Chemie Novenyvedoszer Gyarto Ertekesito est Forgalmazo Kft.
公开号：US06320085B1
公开（公告）日：2001-11-20
The subject matter of the invention is the process for the preparation of mixed ethers of formula I, wherein Ar represents an aromatic or one or more heteroatom-containing moiety, optionally substituted by one or more C1-4 alkoxy, methylenedioxy, C1-4 alkyl, halogen, C1-4 haloalkyl or nitro-group, and/or condensed with a benzene ring; R1 and R2 independently mean hydrogen, C1-4 alkyl, C1-4 haloalkyl, C2-4 alkenyl, phenyl, substituted phenyl, C3-6 cycloalkyl group, R3 means C3-6 alkynyl, optionally substituted by one or more C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C1-6 haloalkyl group, or halogen atom, R3 also means a C1-4 alkyloxy-C1-4 alkyloxy-C1-4 alkyl group. The process comprises the step of reacting the compounds of general formula II with 1 to 3 molar equivalent of the alcohol of general formula IlI in the presence of acid, a Lewis acid, a metal oxide or a metal carbonate, X means hydroxy, halogen or sulphonester leaving group, the resulting ether of general formula I is isolated, if desired, stabilized by the addition of a base and/or an antioxidant; and if desired the excess of the alcohol is recovered.
The present invention is directed to piperidinone carboxamide azaindane derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.
AMINE COMPOUND AND USE THEREOF FOR MEDICAL PURPOSES
申请人：MITSUBISHI TANABE PHARMA CORPORATION
公开号：US20140296183A1
公开（公告）日：2014-10-02
A novel amine compound represented by the following formula (I), which is superior in immunosuppressive action, rejection suppressive action and the like, and shows reduced side effects such as bradycardia and the like, or a pharmaceutically acceptable acid addition salt thereof, or hydrates thereof, or solvate, as well as a pharmaceutical composition containing this compound and a pharmaceutically acceptable carrier.
wherein R is a hydrogen atom or P(═O)(OH)
2
, X is an oxygen atom or a sulfur atom, Y is CH
2
CH
2
or CH═CH, R
1
is cyano or alkyl having a carbon number of 1 to 4 and substituted by a halogen atom(s), R
2
is alkyl having a carbon number of 1 to 4 and optionally substituted by a hydroxyl group(s) or a halogen atom(s), R
3
and R
4
may be the same or different and each is a hydrogen atom or alkyl having a carbon number of 1 to 4, and n is 5-8.
IMIDAZOTHIADIAZOLE AND IMIDAZOPYRAZINE DERIVATIVES AS PROTEASE ACTIVATED RECEPTOR 4 (PAR4) INHIBITORS FOR TREATING PLATELET AGGREGATION
申请人：BRISTOL-MYERS SQUIBB COMPANY
公开号：US20150094297A1
公开（公告）日：2015-04-02
The present invention provides thiazole compounds of Formula I wherein W, Y, R
0
, R
2
, R
4
, R
5
, R
6
, R
7
, X
1
, X
2
, X
3
and X
4
are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments for treating or preventing thromboembolic disorders.
