Drug Indications Module

Drug Indications Module Identification of all drug products available to treat a specific condition. 

Endothelin converting enzyme (ECE) has yet to be fully characterized. It is a membrane-located enzyme found in the vascular endothelium. It is essential in the production of endothelin in the body since it converts the inactive precursor big ET-1 to endothelin-1. It is an unusual enzyme because it cleaves at a Tyr-Val link. Like endopeptidase-24.11, it is inhibited by phosphoramidon (so is a metalloproteinase), and these two enzymes are often colocated. Furthermore, monoclonal antibody co-precipitation studies indicate they share a common epitope, and a homology to the extent of about 39%, ECE is also similar to the bacterial metalloprotease thermolysin, but is more specific. If a specific inhibitor is discovered that can act in vivo, then clearly such a drug could modulate endothelin production throughout the body, which would have important consequences (e.g. in antihypertensive therapy). 

Oxcarbazepine Modulate sodium channels Loading dose Not recommended due to excessive adverse effects Maintenance dose 600-1200 mg/day. Start at 300 mg twice daily and titrate upward as indicated by response Half-life Not established Parent drug 2 hours 1 0-monohydroxy metabolite 9 hours Apparent volume of distribution 0.5-0.7 L/kg Protein binding 40% Primary elimination route Hepatic Diplopia, dizziness, somnolence Hyponatremia, 25-30% cross sensitivity in patients with hypersensitivity to carbamazepine... 

Figure 12 Schematic representation for reversibly changing drug permeation through membranes by external modulation. M, indicates the diffused amount of drug at time t. 

Because of the continued need for better drugs to treat depression and the opportunities for new clinical indications, efforts to discover novel monoamine reuptake inhibitors continue unabated. This review will highlight developments in the discovery of novel agents that work via monoamine reuptake inhibition primarily based on publications that have appeared between 2005 and early 2007. New clinical indications for monoamine reuptake inhibitors will also be highlighted. A comprehensive review of publications on monoamine reuptake inhibitors between 2000 and July 2005 is available [3]. Approaches for the treatment of depression involving the augmentation of monoamine reuptake inhibitors with other CNS receptor modulators, and non-monoamine-based strategies have also been reviewed recently [6-8]. 

A large number of patent applications has been filed, most recently describing imidazothiazoles [70], oxazolopyridines [71], benzimidazoles [72], benzothiazoles [73] and imidazopyridines [74] as sirtuin modulators, however it is not yet possible to determine which compound classes will prove most promising. Overall, due to their potential applications as new drug candidates for various indications, the class III HDAC inhibitors are currently a rapidly growing field of interest. 

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