ERIBULIN MESYLATE (HALAVEN®) is a microtubule dynamics inhibitor. It is a synthetic analog of halichondrin B, a product isolated from the marine sponge Halichondria okadai. ERIBULIN MESYLATE (HALAVEN®) inhibits the growth phase of microtubules without affecting the shortening phase and sequesters tubulin into nonproductive aggregates. It exerts its effects via a tubulin-based antimitotic mechanism leading to G2/M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death after the prolonged mitotic blockage. ERIBULIN MESYLATE (HALAVEN®) is indicated for the treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. It is also indicated for the treatment of patients with unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen.

Ceftaroline is a fifth-generation broad-spectrum cephalosporin with potent antimicrobial activity against Gram-positive and Gram-negative pathogens. Ceftaroline is the bioactive metabolite of ceftaroline fosamil, an N-phosphonoamino water-soluble cephalosporin prodrug, which is rapidly converted in vivo upon the hydrolysis of the phosphonate group by plasma phosphatises. Ceftaroline fosamil is being developed by Forest Laboratories, under a license from Takeda. In 2010, the U.S. Food and Drug Administration (FDA) approved ceftaroline fosamil for use in the treatment of acute bacterial skin and skin structure infections as well as community-acquired pneumonia. Ceftaroline has bactericidal activity against methicillin-resistant Staphylococcus aureus, therefore serving as an attractive alternative agent for the treatment of methicillin-resistant Staphylococcus aureus bacteremia when approved agents are contraindicated or treatment failures have occurred. Like other β-lactams, ceftaroline’s mechanism of action is mediated by binding to the penicillin-binding protein (PBP), the enzyme mediating the cross-linking transpeptidation of the peptidoglycan which are the terminal steps in completing formation of the bacterial cell wall. MRSA strains have a mutated PBP2a which prohibits β-lactam antibiotics from accessing its active site that mediates the transpeptidation reaction. Ceftaroline possesses an ethoxyimino side-chain mimicking a portion of a cell wall structure, which acts as a “Trojan horse”, allosterically opening and facilitating access to the active site of the PBP2a. Based on clinical trial data to date, ceftaroline appears to be safe and well-tolerated. Since ceftaroline is a cephalosporin, it has caused serious hypersensitivity reactions in patients who are allergic to cephalosporins and among some patients with penicillin allergies.

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.

Saxagliptin is an orally active hypoglycemic (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. FDA approved on July 31, 2009. Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor antidiabetic for the treatment of type 2 diabetes. DPP-4 inhibitors are a class of compounds that work by affecting the action of natural hormones in the body called incretins. Incretins decrease blood sugar by increasing consumption of sugar by the body, mainly through increasing insulin production in the pancreas, and by reducing production of sugar by the liver. [Bristol-Myers Squibb Press Release] DPP-4 is a membrane associated peptidase which is found in many tissues, lymphocytes and plasma. DPP-4 has two main mechanisms of action, an enzymatic function and another mechanism where DPP-4 binds adenosine deaminase, which conveys intracellular signals via dimerization when activated. Saxagliptin forms a reversible, histidine-assisted covalent bond between its nitrile group and the S630 hydroxyl oxygen on DPP-4. The inhibition of DPP-4 increases levels active of glucagon like peptide 1 (GLP-1), which inhibits glucagon production from pancreatic alpha cells and increases production of insulin from pancreatic beta cells.

Dronedarone is an antiarrhythmic that is FDA approved for the treatment of atrial fibrillation in patients in sinus rhythm with a history of paroxysmal or persistent atrial fibrillation (AF). Dronedarone is multichannel blocker. Common adverse reactions include abdominal pain, diarrhea, indigestion, nausea, vomiting, asthenia and raised serum creatinine. Dronedarone has potentially important pharmacodynamics interactions: Digoxin: Consider discontinuation or halve dose of digoxin before treatment and monitor; Calcium channel blockers (CCB): Initiate CCB with low dose and increase after ECG verification of tolerability; Beta-blockers: May provoke excessive bradycardia, Initiate with low dose and increase after ECG verification of tolerability.

Lumefantrine is an antimalarial agent used to treat acute uncomplicated malaria. It is administered in combination with artemether for improved efficacy (Coartem tablets). Lumefantrine is a blood schizonticide active against erythrocytic stages of Plasmodium falciparum. The exact mechanism by which lumefantrine exerts its antimalarial effect is unknown. The most common adverse reactions of Coartem in adults are headache, anorexia, dizziness, asthenia, arthralgia and myalgia.

Iloperidone, also known as Fanapt, Fanapta, and previously known as Zomaril, is an atypical antipsychotic for the treatment of schizophrenia. Iloperidone shows high affinity and maximal receptor occupancy for dopamine D2 receptors in the caudate nucleus and putamen of the brains of schizophrenic patients. The improvement in cognition is attributed to iloperidone's high affinity for α adrenergic receptors. Iloperidone also binds with high affinity to serotonin 5-HT2a and dopamine 3 receptors. Iloperidone binds with moderate affinity to dopamine D4, serotonin 5-HT6 and 5-HT7, and norepinephrine NEα1 receptors. Furthermore, iloperidone binds with weak affinity to serotonin 5-HT1A, dopamine D1, and histamine H1 receptors. Iloperidone is indicated for the treatment of acute schizophrenia.

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.

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.

Dextromilnacipran (1R, 2S/F2696) is an enantiomer of milnacipran, a serotonin/norepinephrine (5-HT/NE) reuptake inhibitor. Dextromilnacipran is pharmacologically less active as compared with racemic mixture and levomilnacipran (1S, 2R/F2695).