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

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

    {{facet.count}}
    {{facet.count}}

Showing 251 - 260 of 34144 results

Topotecan, a semi-synthetic derivative of camptothecin (a plant alkaloid obtained from the Camptotheca acuminata tree), is an anti-tumor drug with topoisomerase I-inhibitory activity similar to irinotecan. DNA topoisomerases are enzymes in the cell nucleus that regulate DNA topology (3-dimensional conformation) and facilitate nuclear processes such as DNA replication, recombination, and repair. During these processes, DNA topoisomerase I creates reversible single-stranded breaks in double-stranded DNA, allowing intact single DNA strands to pass through the break and relieve the topologic constraints inherent in supercoiled DNA. The 3'-DNA terminus of the broken DNA strand binds covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the unaltered topoisomers that allow transcription to proceed. Topotecan interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells can be affected by the medicine, other effects may also occur. Unlike irinotecan, topotecan is found predominantly in the inactive carboxylate form at neutral pH and it is not a prodrug. Topotecan has the same mechanism of action as irinotecan and is believed to exert its cytotoxic effects during the S-phase of DNA synthesis. Topoisomerase I relieves torsional strain in DNA by inducing reversible single strand breaks. Topotecan binds to the topoisomerase I-DNA complex and prevents religation of these single strand breaks. This ternary complex interferes with the moving replication fork, which leads to the induction of replication arrest and lethal double-stranded breaks in DNA. As mammalian cells cannot efficiently repair these double strand breaks, the formation of this ternary complex eventually leads to apoptosis (programmed cell death). Topotecan mimics a DNA base pair and binds at the site of DNA cleavage by intercalating between the upstream (−1) and downstream (+1) base pairs. Intercalation displaces the downstream DNA, thus preventing religation of the cleaved strand. By specifically binding to the enzyme–substrate complex, Topotecan acts as an uncompetitive inhibitor. Topotecan is used for the treatment of advanced ovarian cancer in patients with disease that has recurred or progressed following therapy with platinum-based regimens. Also used as a second-line therapy for treatment-sensitive small cell lung cancer, as well as in combination with cisplatin for the treatment of stage IV-B, recurrent, or persistent cervical cancer not amenable to curative treatment with surgery and/or radiation therapy. Topotecan is sold under the trade name Hycamtin.

Class (Stereo):
CHEMICAL (RACEMIC)



Donepezil, marketed under the trade name Aricept, is a medication used in the palliative treatment of Alzheimer's disease. Aricept is indicated for the treatment of dementia of the Alzheimer’s type. Efficacy has been demonstrated in patients with mild to moderate Alzheimer’s Disease, as well as in patients with severe Alzheimer’s Disease. Donepezil is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by acetylcholinesterase. Donepezil has been tested in other cognitive disorders including Lewy body dementia and Vascular dementia, but it is not currently approved for these indications. Donepezil has also been studied in patients with Mild Cognitive Impairment, schizophrenia, attention deficit disorder, post-coronary bypass cognitive impairment, cognitive impairment associated with multiple sclerosis, and Down syndrome.
Azelastine, a phthalazine derivative, is an antihistamine and mast cell stabilizer. Azelastine is oxidatively metabolized to the principal active metabolite, desmethylazelastine, by the cytochrome P450 enzyme system. It is indicated for the relief of the symptoms of seasonal allergic rhinitis and perennial allergic rhinitis. The most common adverse reactions are: pyrexia, dysgeusia, nasal discomfort, epistaxis, headache, sneezing, fatigue, somnolence, upper respiratory infection, cough, rhinalgia, vomiting, otitis media, contact dermatitis, and oropharyngeal pain. Concurrent use of Azelastine with alcohol or other central nervous system depressants should be avoided because reductions in alertness and impairment of central nervous system performance may occur.
Status:
First approved in 1996

Class (Stereo):
CHEMICAL (ABSOLUTE)



Cidofovir is an antiviral nucleotide analogue with significant activity against cytomegalovirus (CMV) and other herpesviruses. Cidofovir suppresses cytomegalovirus (CMV) replication by selective inhibition of viral DNA synthesis. Biochemical data support selective inhibition of CMV DNA polymerase by cidofovir diphosphate, the active intracellular metabolite of cidofovir. Incorporation of cidofovir into the growing viral DNA chain results in reductions in the rate of viral DNA synthesis. Cidofovir is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome.
Meropenem (generic name: meropenem hydrate) is a carbapenem antibiotic for injection showing a strong antibacterial activity to a wide range of bacteria strains from Gram-positive bacteria, Gram-negative bacteria to anaerobic bacteria. It is used as single agent therapy for the treatment of the following infections: complicated skin and skin structure infections due to Staphylococcus aureus (b-lactamase and non-b-lactamase producing, methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci. This drug also used in case of Intra-abdominal Infections for the treatment complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus species. In addition is used the treatment of bacterial meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae (b-lactamase and non-b-lactamase-producing isolates), and Neisseria meningitides. The bactericidal activity of meropenem results from the inhibition of cell wall synthesis. Meropenem readily penetrates the cell wall of most Gram-positive and Gram-negative bacteria to reach penicillin-binding-protein (PBP) targets. Its strongest affinities are toward PBPs 2, 3 and 4 of Escherichia coli and Pseudomonas aeruginosa; and PBPs 1, 2 and 4 of Staphylococcus aureus. Meropenem has significant stability to hydrolysis by β-lactamases, both penicillinases and cephalosporinases produced by Gram-positive and Gram-negative bacteria. Meropenem should not be used to treat methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant Staphylococcus epidermidis (MRSE). Meropenem product with such superior effectiveness and safety has been approved for marketing by 100 countries or more in the world (as of March 2004) since its first launch in Italy in 1994.
Nevirapine is a non-nucleoside reverse transcriptase inhibitor (nNRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). HIV-2 RT and eukaryotic DNA polymerases (such as human DNA polymerases alpha, beta, or sigma) are not inhibited by nevirapine. Nevirapine is, in general, only prescribed after the immune system has declined and infections have become evident. It is always taken with at least one other HIV medication such as Retrovir or Videx. The virus can develop resistance to nevirapine if the drug is taken alone, although even if used properly, nevirapine is effective for only a limited time. Nevirapine binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site. The activity of nevirapine does not compete with template or nucleoside triphosphates. Nevirapine is used for use in combination with other antiretroviral drugs in the ongoing treatment of HIV-1 infection.

Class (Stereo):
CHEMICAL (RACEMIC)


Conditions:

Nisoldipine is a 1,4-dihydropyridine derivative with an outstanding vascular selectivity. As a specific calcium antagonist, it shortens the action potential and causes electromechanical uncoupling in ventricular myocardium. However, this effect, resulting in a negative inotropic action, appears at 100–1000 times higher concentrations of nisoldipine in comparison with its inhibition of calcium-dependent vascular contractions. Detailed analyses of pharmacological effects revealed additional properties such as enhancement of sodium excretion, an interaction with the reninangiotensin-aldosterone system and a protective effect against acute renal ischaemia, that may contribute to its therapeutic efficacy. Nisoldipine was developed at Bayer then licensed to Zeneca and marketed in the United States as SULAR. SULAR is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents. The mechanism of the therapeutic effect of nisoldipine is complex. It involves a decrease of the total peripheral vascular resistance (reduction of afterload) and an increase in coronary blood flow. Moreover, nisoldipine obviously normalises the impaired volume homoeostasis by improving renal function and thus reduces the need for activation of the ANP system. In the advanced stages of hypertension, nisoldipine prevents deleterious calcium overload and the resulting tissue damage.
Iopromide is a molecule used as a contrast medium. It is a low osmolar, non-ionic contrast agent for intravascular use. It is commonly used in radiographic studies such as intravenous urograms, brain computer tomography (CT) and CT pulmonary angiograms (CTPAs). It appears to increase the risk of biguanide induced lactic acidosis. Interleukins are associated with an increased prevalence of delayed hypersensitivity reactions after iodinated contrast agent administration. Most common adverse reactions (>1%) are headache, nausea, injection site and infusion site reactions, vasodilatation, vomiting, back pain, urinary urgency, chest pain, pain, dysgeusia, and abnormal vision.
Losartan is a selective, competitive angiotensin II receptor type 1 (AT1) antagonist. Losartant is recommended as one of several preferred agents for the initial management of hypertension. Administration of losartan reduces the risk of stroke in patients with hypertension and left ventricular hypertrophy. Losartan is indicated for the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria in patients with type 2 diabetes and a history of hypertension.
Dexlansoprazole (trade names Kapidex, Dexilant) is a proton pump inhibitor (PPI) that is marketed by Takeda Pharmaceuticals for the treatment of erosive esophagitis and gastro-oesophageal reflux disease. Dexlansoprazole is used to heal and maintain healing of erosive esophagitis and to treat heartburn associated with gastroesophageal reflux disease (GERD). It lasts longer than lansoprazole, to which it is chemically related, and needs to be taken less often. Dexlansoprazole is supplied for oral administration as a dual delayed-release formulation in capsules and orally disintegrating tablets. The capsules and tablets contain dexlansoprazole in a mixture of two types of enteric-coated granules with different pH-dependent dissolution profiles. The most significant adverse reactions (≥2%) reported in clinical trials were diarrhea, abdominal pain, nausea, upper respiratory tract infection, vomiting, and flatulence.