Nitisinone, 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) is a triketone with herbicidal activity. Orfadin® capsules contain nitisinone used in the treatment of hereditary tyrosinemia type 1 (HT-1). Nitisinone is a competitive inhibitor of 4-hydroxyphenyl-pyruvate dioxygenase, an enzyme upstream of fumarylacetoacetase in the tyrosine catabolic pathway. By inhibiting the normal catabolism of tyrosine in patients with HT-1, nitisinone prevents the accumulation of the catabolic intermediates maleylacetoacetate and fumarylacetoacetate. In patients with HT-1, these catabolic intermediates are converted to the toxic metabolites succinylacetone and succinylacetoacetate, which are responsible for the observed liver and kidney toxicity. Succinylacetone can also inhibit the porphyrin synthesis pathway leading to the accumulation of 5-aminolevulinate, a neurotoxin responsible for the porphyric crises characteristic of HT-1. Zeneca Agrochemicals and Zeneca Pharmaceuticals made NTBC available for clinical use and, with the approval of the Swedish Medical Products Agency, a seriously ill child with an acute form of tyrosinaemia type 1 was successfully treated in February 1991. Nitisinone is investigated as a potential treatment for other disorders of tyrosine metabolism including alkaptonuria.

Escitalopram is one of a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs). Escitalopram, also known by the brand names Lexapro and Cipralex among others, is an antidepressant. The mechanism of antidepressant action of escitalopram, the S-enantiomer of racemic citalopram, is presumed to be linked to potentiation of serotonergic activity in the central nervous system (CNS) resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT). In vitro and in vivo studies in animals suggest that escitalopram is a highly selective serotonin reuptake inhibitor (SSRI) with minimal effects on norepinephrine and dopamine neuronal reuptake. Escitalopram is at least 100-fold more potent than the R-enantiomer with respect to inhibition of 5-HT reuptake and inhibition of 5-HT neuronal firing rate. LEXAPRO (escitalopram) is indicated for the treatment of major depressive disorder and generalized anxiety disorder .

Dutasteride is a synthetic 4-azasteroid compound that is a selective inhibitor of both the type 1 and type 2 isoforms of steroid 5 alpha-reductase (5AR), intracellular enzymes that convert testosterone to 5 alpha-dihydrotestosterone (DHT). Type I 5a-reductase is predominant in the sebaceous glands of most regions of skin, including scalp, and liver. Type I 5a-reductase is responsible for approximately one-third of circulating DHT. The Type II 5a-reductase isozyme is primarily found in prostate, seminal vesicles, epididymides, and hair follicles as well as liver, and is responsible for two-thirds of circulating DHT. Dutasteride inhibits the conversion of testosterone to 5 alpha-dihydrotestosterone (DHT), which is the androgen primarily responsible for the initial development and subsequent enlargement of the prostate gland. Testosterone is converted to DHT by the enzyme 5 alpha-reductase, which exists as 2 isoforms, type 1 and type 2. Dutasteride is a competitive and specific inhibitor of both type 1 and type 2 5 alpha-reductase isoenzymes, with which it forms a stable enzyme complex. Dissociation from this complex has been evaluated under in vitro and in vivo conditions and is extremely slow. Used for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate gland to improve symptoms, and reduce the risk of acute urinary retention and the need for surgery. Marketed under the brand name Avodart.

Imatinib (GLEEVEC®) is a tyrosine kinase inhibitor and antineoplastic agent that inhibits the BCR-ABL tyrosine kinase, the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome abnormality in chronic myeloid leukaemia (CML). It inhibits proliferation and induces apoptosis in BCR-ABL positive cell lines as well as fresh leukemic cells from Philadelphia chromosome positive CML. Imatinib (GLEEVEC®) inhibits colony formation in assays using ex vivo peripheral blood and bone marrow samples from CML patients. It is also an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-kit, and inhibits PDGF- and SCF-mediated cellular events. In vitro, imatinib (GLEEVEC®) inhibits proliferation and induces apoptosis in gastrointestinal stromal tumor (GIST) cells, which express an activating c-kit mutation.

Caspofungin is an echinocandin antifungal drug, which is approved and is sold under the brand worldwide name cancidas. Caspofungin inhibits the synthesis of beta (1,3)-D-glucan, an essential component of the cell wall of susceptible Aspergillus species and Candida species. Beta (1,3)-D-glucan is not present in mammalian cells. Cancidas is indicated for the treatment of candidemia and the following candida infections: intra-abdominal abscesses, peritonitis, and pleural space infections in adult and pediatric patients. Also is indicated for the treatment of esophageal candidiasis in adult and pediatric patients and for the treatment of invasive aspergillosis in adult and pediatric patients, but has not been studied as initial therapy for invasive aspergillosis.

Formoterol is a long-acting selective beta2-adrenergic receptor agonist (beta2-agonist). Inhaled formoterol fumarate acts locally in the lung as a bronchodilator. In vitro studies have shown that formoterol has more than 200-fold greater agonist activity at beta2-receptors than at beta1- receptors. Although beta2-receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta1-receptors are the predominant receptors in the heart, there are also beta2-receptors in the human heart comprising 10%-50% of the total beta-adrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective beta2- agonists may have cardiac effects. The pharmacologic effects of beta2-adrenoceptor agonist drugs, including formoterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3', 5'-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibits the release of pro-inflammatory mast-cell mediators such as histamine and leukotrienes. Formoterol also inhibits histamine-induced plasma albumin extravasation in anesthetized guinea pigs and inhibits allergen-induced eosinophil influx in dogs with airway hyper-responsiveness. The relevance of these in vitro and animal findings to humans is unknown. Formoterol is used for use as long-term maintenance treatment of asthma in patients 6 years of age and older with reversible obstructive airways disease, including patients with symptoms of nocturnal asthma, who are using optimal corticosteroid treatment and experiencing regular or frequent breakthrough symptoms requiring use of a short-acting bronchodilator. Not indicated for asthma that can be successfully managed with occasional use of an inhaled, short-acting beta2-adrenergic agonist. Also used for the prevention of exercise-induced bronchospasm, as well as long-term treatment of bronchospasm associated with COPD. Marketed as Foradil Aerolizer.

Galantamine (RAZADYNE®, galantamine hydrobromide) is a benzazepine derived from norbelladine. It is found in Galanthus and other Amaryllidaceae. It is a reversible, competitive acetylcholinesterase inhibitor that is used for the treatment of mild to moderate dementia of the Alzheimer’s type. Although the etiology of cognitive impairment in Alzheimer’s disease is not fully understood, it has been reported that acetylcholine-producing neurons degenerate in the brains of patients with Alzheimer’s disease. The degree of this cholinergic loss has been correlated with degree of cognitive impairment and density of amyloid plaques (a neuropathological hallmark of Alzheimer’s disease). While the precise mechanism of galantamine’s (RAZADYNE®, galantamine hydrobromide) action is unknown, it 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. If this mechanism is correct, galantamine’s (RAZADYNE®, galantamine hydrobromide) effect may lessen as the disease process advances and fewer cholinergic neurons remain functionally intact. There is no evidence that galantamine (RAZADYNE®, galantamine hydrobromide) alters the course of the underlying dementing process.

Ertapenem is a carbapenem antibiotic marketed by Merck as Invanz. The bactericidal activity of ertapenem results from the inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin binding proteins (PBPs). In Escherichia coli, it has strong affinity toward PBPs 1a, 1b, 2, 3, 4 and 5 with preference for PBPs 2 and 3. Ertapenem has been designed to be effective against Gram-negative and Gram-positive bacteria. The most common drug-related adverse experiences in patients treated with INVANZ, including those who were switched to therapy with an oral antimicrobial, were diarrhea (5.5%), infused vein complication (3.7%), nausea (3.1%), headache (2.2%), vaginitis in females (2.1%), phlebitis/thrombophlebitis (1.3%), and vomiting (1.1%). The coadministration with probenecid to extend the half-life of ertapenem is not recommended.

(R)-9-(2-Phosphonylmethoxypropyl)adenine (PMPA known as tenofovir) is an antiviral drug. Diphosphate of PMPA acts as a selective inhibitor of the HIV-1 reverse transcriptase. Tenofovir disoproxil was approved for clinical use for the treatment of HIV infection (AIDS) and chronic HBV infection.

Zoledronic acid (Reclast, Aclasta, Zometa) is an intravenous, highly potent amino-bisphosphonate approved worldwide, including in the USA, EU and Japan for use in patients with primary or secondary osteoporosis or low bone mass (approved indications vary between countries). Its high affinity to and long half-life in bone, and long duration of action allow for once-yearly administration, which has the potential to improve adherence to therapy. Zoledronic acid once yearly for up to 3 years improved bone mineral density (BMD) at several skeletal sites, reduced fracture risk and bone turnover, and/or preserved bone structure and mass relative to placebo in clinical studies in patients with primary or secondary osteoporosis. While additional benefits were seen when treatment was continued for up to 6 years, as evidenced by a reduced risk of vertebral fractures and higher BMD relative to 3 years’ therapy, there was the minimal advantage of treatment beyond 6 years. Therefore, in patients with low fracture risk, treatment discontinuation should be considered after approximately 5 years’ therapy. Zoledronic acid administered annually or once in 2 years was also effective in preventing bone loss in patients with low bone mass. Zoledronic acid was generally well tolerated, with the most common adverse events (AEs) being transient, mild-to-moderate post-infusion symptoms, which decreased with subsequent infusions.