Therapeutically used drugs

Cytochrome P450 enzymes have been the subject of a number of recent reviews in which their mechanism and scope of action are covered in much detail [1, 6, 10, 11]. The reader is referred to these articles for a more thorough account of the mechanism and reactivity of cytochrome P450 enzymes, while we present a few representative examples of cytochrome P450-catalyzed epoxidation below. The enzymes we chose are all involved in the biosynthesis of polyketide natural products. Polyketides are a large, structurally diverse family of compounds and have provided a wealth of therapeutically useful drugs and drug leads. 

Brogden RN, Goa KL Flumazenil a preliminary review of its benzodiazepine antagonist properties, intrinsic activity and therapeutic use. Drugs 35 448 67, 1988... 

Y. W. Chien, Human Insubn Basic Sciences to Therapeutic Uses , Drug Dev. Ind. Pharm. 1996, 22, 753-789. 

Maton PN, Burton ME. Antacids revisited a review of their clinical pharmacology and recommended therapeutic use. Drugs 1999 57(6) 855-70. 

Campoli-Richards D.M., J.P. Monk, and A. Price (1988). Ciprofloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 35 373 147. 

Bellantuono, C., Reggi, V, Tognoni, G., and Garattini, S. (1980) Benzodiazepines clinical pharmacology and therapeutic use. Drugs 19 195-219... 

Many therapeutically useful drugs are also used as laboratory tools. Marine origin is indicated in boldface, even in obvious cases. 

F. D. Hart, E. C. Huskinson (1984), Non-steroidal antiinflammatory drugs current status and rational therapeutic use. Drugs 27 232-255. 

Mirakhur RK. Newer neuromuscular blocking drugs An overview of their clinical pharmacology and therapeutic use. Drugs 1992 44 182-99. 

Ozmen L, Roman D, Fountoualakis M, Schmid G, Ryffel B, Garotta G. Soluble interferon-gamma receptor a therapeutically useful drug for systemic lupus erythematosus. J Interferon Res 1994 14(5) 283-284. 

R.N. Brogden, and R.C. Heel, Human insulins A review of its biological activity, pharmacokinetic and therapeutic use. Drugs 34 350-371, 1987. 

The guanidinothiazole group appears to confer high affinity at the H2-receptor, and many active derivatives are now known. Only one of these, however, has become a therapeutically useful drug this is a sulfamidoamidine analogue discovered in the laboratories of the Japanese Company, Yamanouchi. This compound, famotidine (YM 11170 Fig. 1.2) is about 30 times more potent [15] than cimeti-dine in man, and is marketed in Japan as Caster and in Western countries by Merck Sharp and Dohme (under license from Yamanouchi), under the trademark Pepcid . 

Dundee JW, Halliday NJ, Harper KW, Brogden RN. Midazolam. A review of its pharmacological properties and therapeutic use. Drugs 1984 28(6) 519—43. 

Fulton B, Benfleld P. Moclobemide. An update of Its pharmacological properties and therapeutic use. Drugs 1996 52 450-74. 

Anderson JL, Harrison DC, Meffin PJ, Winkle RA. Antiarrhythmic drugs clinical pharmacology and therapeutic uses. Drugs 1978 15(4) 271-309. 

Miller JA, Munro DD. Topical corticosteroids clinical pharmacology and therapeutic use Drugs 1980 19(2) 119-34. 

The first two of these reactions are equally relevant for biotransformation process. Amides are often more stable to enzymatic hydrolysis than the corresponding esters with similar structures. For example, phenyl-acetate is hydrolyzed much faster than acetanilide. In addition, CarbE can hydrolyze therapeutically useful drug esters, such as chloramphenicol succinate, prednisolone succinate, procaine, and methylparaben. 

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