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

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Showing 51 - 60 of 3913 results

Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) which is used for the treatment of HIV-1 infections in treatment-naive patients. It is active against wild-type and NNRTI-resistant HIV-1. Rilpivirine is a diarylpyrimidinethat inhibits HIV-1 replication by non-competitive inhibition of HIV-1 reverse transcriptase (RT). Rilpivirine does not inhibit the human cellular DNA polymerases α, β and γ.

Class (Stereo):
CHEMICAL (ACHIRAL)

Targets:


Deferiprone (trade name Ferriprox) is an iron chelator indicated for the treatment of patients with transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate. Deferiprone is an orally bioavailable bidentate ligand with iron chelating activity. Deferiprone binds to iron in a 3:1 (ligand:iron) molar ratio. By binding to iron, deferiprone is able to remove excess iron from the body. All the adverse effects of deferiprone are considered reversible, controllable and manageable. These include agranulocytosis with frequency of about 0.6%, neutropenia 6%, musculoskeletal and joint pains 15%, gastrointestinal complains 6% and zinc deficiency 1%.
Vilazodone is a serotonergic antidepressant. The mechanism of the antidepressant effect of vilazodone is not fully understood but is thought to be related to its inhancement of serotonergic activity in the CNS through selective inhibition of serotonin reuptake. Vilazodone is also a partial agonist at serotonergic 5-HT1A receptors; however, the net result of this action on serotonergic transmission and its role in vilazodone’s antidepressant effect are unknown. The side effects include activation of mania/hypomania in patients with bipolar disorder, seizures can occur with treatment in patients with a seizure disorder.
Ioflupane I-123 (trade name DaTscan) is a radioiodinated cocaine analogue synthesized from a key starting material Sn FP-CT via oxidative iododestannylation with sodium (123I)-iodide. Ioflupane I-123 binds reversibly with high affinity to the dopamine transporter (DaT) protein, a marker for presynaptic terminals in dopaminergic nigrostriatal neurons. It has been developed as a dopamine transporter imaging agent for single photon emission computed tomography (SPECT) which is claimed to be sensitive enough to differentiate changes in the nigrostriatal dopaminergic system in patients with Parkinsonism and healthy controls. DaTSCAN is unable to discriminate between Parkinson's Disease, Multiple System Atrophy and Progressive Supranuclear Palsy. DaTscan is an adjunct to other diagnostic evaluations. Headache, nausea, vertigo, dry mouth, or dizziness of mild to moderate severity as well as hypersensitivity reactions and injection-site pain have been reported. The DaTscan injection may contain up to 6% of free iodide (iodine 123 or I-123). To decrease thyroid accumulation of I-123, the thyroid gland has to be blocked at least one hour before administration of DaTscan because of the long-term risk for thyroid neoplasia. DaTscan was first approved in the European Union (EU) on July 27, 2000. It is also approved in Israel, Switzerland and in the United States (a total of 33 countries).

Class (Stereo):
CHEMICAL (ACHIRAL)



Clobazam belongs to the 1,5-benzodiazepine class of drugs with antiepileptic properties. It has been used to treat anxiety and epilepsy since 1970s. In the US clobazam was approved for marketing in October of 2011 for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome. It is also approved for adjunctive therapy for epilepsy in patients who have not responded to first-line drugs and in children who are refractory to first-line drugs. The mechanism of action for clobazam is not fully understood but is thought to involve what is known as potentiation of GABAergic neurotransmission resulting from binding at a benzodiazepine site at the GABA(A) receptor. Possible side effects: constipation, fever, drowsiness, sedation, ataxia, aggressive behavior, lethargy, drooling, and irritability. Other side effects include: urinary tract infection, pneumonia, cough, dysphagia, dysarthria, bronchitis, insomnia, fatigue, decreased appetite, and increased appetite.
Dalfampridine is a potassium channel blocker, used as a research tool in characterizing subtypes of the potassium channel. Dalfampridine has also been used as a drug, to manage some of the symptoms of multiple sclerosis, and is indicated for symptomatic improvement of walking in adults with several variations of the disease. The mechanism by which dalfampridine exerts its therapeutic effect has not been fully elucidated. Dalfampridine is a broad spectrum potassium channel blocker. In animal studies, dalfampridine has been shown to increase conduction of action potentials in demyelinated axons through inhibition of potassium channels.
Cabazitaxel (JEVTANA®) is an antineoplastic agent belonging to the taxane class and is used to treat people with prostate cancer that has progressed despite treatment with docetaxel. It is prepared by semi-synthesis with a precursor extracted from yew needles (10-deacetylbaccatin III). Cabazitaxel (JEVTANA®) is a microtubule inhibitor. It binds to tubulin and promotes its assembly into microtubules while simultaneously inhibiting disassembly. This leads to the stabilization of microtubules, which results in the inhibition of mitotic and interphase cellular functions. The cell is then unable to progress further into the cell cycle, being stalled at metaphase, thus triggering apoptosis of the cancer cell.
Fingolimod (FTY720) is a sphingosine 1-phosphate receptor modulator indicated and approved for the treatment of relapsing-remitting multiple sclerosis. Fingolimod (trade name Gilenya, Novartis) is metabolized by sphingosine kinase to the active metabolite, fingolimod-phosphate. Fingolimod-phosphate is a sphingosine 1-phosphate receptor modulator, and binds with high affinity to sphingosine 1-phosphate receptors 1, 3, 4, and 5. Fingolimod-phosphate blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which fingolimod exerts therapeutic effects in multiple sclerosis is unknown, but may involve reduction of lymphocyte migration into the central nervous system. Fingolimod was approved as a first-in-class, orally active drug for relapsing multiple sclerosis in 2010, and its applications in other disease conditions are currently under clinical trials.
Levomilnacipran (1S, 2R/F2695) is an enantiomer of milnacipran, a serotonin/norepinephrine (5-HT/NE) reuptake inhibitor. Levomilnacipran is pharmacologically more active as compared with racemic mixture and dextromilnacipran (1R, 2S/F2696). The safety of the drug is also higher than the safety of a racemate, resulting in a beneficial impact on the therapeutic effect. Pierre Fabre and Forest Laboratories are developing levomilnacipran extended release (ER) [FETZIMA™], an enantiomer of milnacipran, for the treatment of major depressive disorder (MDD). In addition, Pierre Fabre (the originator of the compound) is developing the drug to improve recovery in patients with ischaemic stroke.

Class (Stereo):
CHEMICAL (RACEMIC)


Conditions:

Vigabatrin is an anticonvulsant chemically unrelated to other anticonvulsants. Vigabatrin prevents the catabolism of GABA by irreversibly inhibiting the enzyme GABA transaminase. It is an analog of GABA, but it is not a receptor agonist. However, vigabatrin is not a potent inhibitor of GABA-T with a Ki of 10 mM. Vigabatrin increases brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by irreversibly inhibiting enzymes that catabolize GABA (gamma-aminobutyric acid transaminase, GABA-T). Duration of action is determined by rate of GABA-T re-synthesis. Vigabatrin may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels. Although administered as a racemic mixture, only the S(+) enantiomer is pharmacologically active. Vigabatrin is sold under the trade name SABRIL, it is indicated as adjunctive therapy for adults and pediatric patients 10 years of age and older with refractory complex partial seizures who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss.