U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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Showing 11 - 20 of 152 results

Metolazone is a thiazide-like diuretic marketed under the brand names Mykrox and Zaroxolyn. Zaroxolyn is indicated for the treatment of salt and water retention including: • Edema accompanying congestive heart failure; • Edema accompanying renal diseases including the nephrotic syndrome and states of diminished renal function. Zaroxolyn is also indicated for the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class. Metolazone is a quinazoline diuretic, with properties generally similar to the thiazide diuretics. The actions of Metolazone result from interference with the renal tubular mechanism of electrolyte reabsorption. Metolazone acts primarily to inhibit sodium reabsorption at the cortical diluting site and to a lesser extent in the proximal convoluted tubule. Sodium and chloride ions are excreted in approximately equivalent amounts. The increased delivery of sodium to the distal tubular exchange site results in increased potassium excretion. Metolazone does not inhibit carbonic anhydrase. A proximal action of Metolazone has been shown in humans by increased excretion of phosphate and magnesium ions and by a markedly increased fractional excretion of sodium in patients with severely compromised glomerular filtration. This action has been demonstrated in animals by micropuncture studies.
Rifampin is an antibiotic that inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. It is bactericidal and has a very broad spectrum of activity against most gram-positive and gram-negative organisms (including Pseudomonas aeruginosa) and specifically Mycobacterium tuberculosis. It is FDA approved for the treatment of tuberculosis, meningococcal carrier state. Healthy subjects who received rifampin 600 mg once daily concomitantly with saquinavir 1000 mg/ritonavir 100 mg twice daily (ritonavir-boosted saquinavir) developed severe hepatocellular toxicity. Rifampin has been reported to substantially decrease the plasma concentrations of the following antiviral drugs: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. These antiviral drugs must not be co-administered with rifampin. Common adverse reactions include heartburn, epigastric distress, anorexia, nausea, vomiting, jaundice, flatulence, cramps.
Flucytosine (5-flucytosine, Ancobon) is an antifungal agent used for treatment of serious fungal infections caused by Candida or Cryptococcus. A fluorinated cytosine analog it was originally developed as an anti-tumor agent, but was found to be non-effective against tumors. Monotherapy with 5-FC is limited because of the frequent development of pathogens resistance. It is often used in in combination with amphotericin B. The severe side effects of 5-flucytosine include hepatotoxicity and bone-marrow depression. 5-fluorocytosine is a prodrug to the cytotoxic compound 5-fluorouracil. Although the exact mode of action is unknown, it has been proposed that flucytosine acts directly on fungal organisms by competitive inhibition of purine and pyrimidine uptake and indirectly by intracellular metabolism to 5-fluorouracil. Flucytosine is taken up by fungal organisms via the enzyme cytosine permease. Inside the fungal cell, flucytosine is rapidly converted to fluorouracil by the enzyme cytosine deaminase. Fluorouracil exerts its antifungal activity through the subsequent conversion into several active metabolites, which inhibit protein synthesis by being falsely incorporated into fungal RNA or interfere with the biosynthesis of fungal DNA through the inhibition of the enzyme thymidylate synthetase.
Floxuridine is a pyrimidine analog that acts as an inhibitor of the S-phase of cell division. This selectively kills rapidly dividing cells. Floxuridine is an anti-metabolite. Anti-metabolites masquerade as pyramidine-like molecules which prevents normal pyrimidines from being incorporated into DNA during the S phase of the cell cycle. Flurouracil (the end-product of catabolism of floxuridine) blocks an enzyme which converts cytosine nucleosides into the deoxy derivative. In addition, DNA synthesis is further inhibited because fluoruracil blocks the incorporation of the thymdine nucleotide into the DNA strand. Floxuridine is used for palliative management of gastrointestinal adenocarcinoma metastatic to the liver, when given by continuous regional intra-arterial infusion in carefully selected patients who are considered incurable by surgery or other means. Also for the palliative management of liver cancer (usually administered by hepatic intra-arterial infusion).Floxuridine first gained FDA approval in December 1970 under the brand name FUDR. The drug was initially marketed by Roche, which also did a lot of the initial work on 5-fluorouracil. The National Cancer Institute was an early developer of the drug. Roche sold its FUDR product line in 2001 to F H Faulding, which became Mayne Pharma.
Status:
First approved in 1965

Class (Stereo):
CHEMICAL (RACEMIC)


Conditions:

Prilocaine is a local anesthetic that is similar pharmacologically to lidocaine. Prilocaine binds to the intracellular surface of sodium channels which blocks the subsequent influx of sodium into the cell. Action potential propagation and never function is, therefore, prevented. This block is reversible and when the drug diffuses away from the cell, sodium channel function is restored and nerve propagation returns. Prilocaine acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. The antiarrhythmic actions are mediated through effects on sodium channels in Purkinje fibers. Currently, Prilocaine is used most often for infiltration anesthesia in dentistry.
Tegafur (INN, BAN, USAN) is a chemotherapeutic fluorouracil prodrug used in the treatment of cancers. It is a component of the combination drugs tegafur/uracil and tegafur/gimeracil/oteracil. UFT is an anticancer medication composed of a fixed molar ration (1:4) of tegafur and uracil. This drug is commonly used in the treatment of head and neck cancer, gastric cancer, colorectal cancer, hepatic cancer, gallbladder cancer, bile-duct cancer, pancreatic cancer, lung cancer, breast cancer, bladder cancer, prostatic cancer, or uterine cervical cancer. In the body, tegafur is converted into 5-fluorouracil (5-FU), the active antineoplastic metabolite. The mechanism of cytotoxicity of 5-FU is thought to be derived from the fact that 5-fluoro-deoxyuridine-monophosphate (FdUMP), the active metabolite of 5-FU, competes with deoxyuridine-monophosphate (dUMP), thereby inhibiting thymidylate synthase and subsequently DNA synthesis. Another active metabolite of 5-FU, 5-fluorouridine-triphosphate (FUTP) is integrated into cellular RNA, inhibiting RNA function. Uracil, when combined with tegafur, enhances the antitumor activity of 5-FU due to higher 5-FU concentrations in the tumor tissue versus normal surrounding tissue compared with tegafur alone. Uracil inhibits degradation of the released 5-FU. The combination of these two drugs enhances the antitumor activity of Tegafur.
Cocaine is an alkaloid ester extracted from the leaves of plants including coca. Cocaine is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Cocaine is addictive due to its effect on the reward pathway in the brain. After a short period of use, there is a high risk that dependence will occur. Its use also increases the risk of stroke, myocardial infarction, lung problems in those who smoke it, blood infections, and sudden cardiac death. Cocaine sold on the street is commonly mixed with local anesthetics, cornstarch, quinine, or sugar which can result in additional toxicity. Following repeated doses, a person may have decreased the ability to feel pleasure and be very physically tired. Cocaine acts by inhibiting the reuptake of serotonin, norepinephrine, and dopamine. This results in greater concentrations of these three neurotransmitters in the brain. It can easily cross the blood-brain barrier and may lead to the breakdown of the barrier.
Menthyl lactate is derived from menthol, a compound that comes from peppermint oil, or is made synthetically. Menthol has a natural cooling effect, which makes it useful as a topical analgesic to treat skin irritation, pain, itching or sunburn. Despite its cooling benefits, menthol can be a skin irritant. Like menthol, menthyl lactate is cooling, but it causes less skin irritation than menthol. Menthyl lactate also has a refreshing, minty taste. For this reason, some manufacturers use it as a flavoring ingredient. The compound is recommended for use as a flavor in concentrations of 0.005% to 0.2% and in cosmetic and other external products in concentrations ranging from 0.2% to 2.0%. Menthyl lactate is a known compound available e.g. from Haarmann & Reimer GmbH (Germany) under the name FRESCOLAT, Type ML.
Status:
Investigational
Source:
NCT00839631: Phase 1 Interventional Completed Solid Tumors
(2009)
Source URL:

Class (Stereo):
CHEMICAL (ACHIRAL)


m-Chlorophenylpiperazine (meta-chlorophenylpiperazine or mCPP) is a psychoactive substance, which is illegal in many countries but can be found on the black market. It induces endocrine, neurological and psychiatric effects. mCPP is a partial agonist at the 5-HT2C receptor but antagonized the 5-HT2B and 5-HT3 receptors. mCPP is also an active metabolite of the drug trazodone, which is used as an effective antidepressant drug with a broad therapeutic spectrum, including anxiolytic efficacy. It is known, that mCPP induces migraine attacks and that the decrease of food intake induced by the mCPP depends on its ability to act as a serotonin agonist is a brain.

Showing 11 - 20 of 152 results