Natural soft drugs

Derivatives of natural hormones and other biologically active agents such as neurotransmitters have well-developed mechanisms for their disposition and, therefore, can be considered natural soft drugs (e.g., hydrocortisone, dopamine). Because their metabolism is usually fast and their transport is specific, they can become useful as drugs only if sustained, local, or site-specific delivery is developed for them. Compounds designed for such purposes can also be considered pro-soft drugs. 

A possible example for sustained chemical release at the site of application for hydrocortisone (116), a natural soft drug, is shown in Fig. 15.29. The 4,5-unsaturated 3-ketone group, being essential for binding and activity, is a good target for modification. Spirothiazo-lidine derivatives (113)were selected (230) be-... 

Figure 15.29. Hydrocortisone (116) can be regarded as a natural soft drug, and a spirothiazolidine derivative (113) serves as apro-soft drug for controlled release. Opening of the thiazolidine ring (114) is followed by disulfide bridging (115) to trap the steroid at the site of application.

There is a frequent misconception regarding soft drugs, particularly soft steroids, that has to be clarified. Often, the soft nature is associated with fast hydrolytic degradation, but this is not necessarily so. If hydrolysis is too rapid, then only weak activity may be ob-... 

Caffeine is an addictive drug used in soft drinks as a stimulant. It occurs naturally in coffee, tea, and chocolate. 

Any formal models of the conduct of research work and success are often soft or fuzzy in nature, and so may be distrusted by those used to hard evidence. There is a particular distrust of opaque, black box solutions, and numerate managers rightly demand to see the detailed assumptions made in any decision analysis. The most controversial assumptions tend to be those about project future costs, chance of success, and potential value within drug... 

The implication of these problems is daunting and has led researchers to overlook some of the nasty details and to develop what might be called practical strategies . This situation is just another example of the heuristic nature of many of the computational methods employed in biological research in general and drug research in particular. What is described in this chapter is a practical procedure based on a soft, heuristic approach to the problem of compound acquisition that has been implemented and used at Pharmacia over the last several years. 

Caffeine is the most widely consumed stimulant drug in the world. It occurs naturally in coffee, tea, and the cola nut and is added to many soft drinks. Many of us consume coffee and soft drinks because of the desirable stimulatory effects produced by caffeine many of us have consumed too much caffeine and felt the consequences. The undesirable effects of caffeine, the agitation, the inability to concentrate, the mild tremors, and the general unpleasantness, are a form of neurotoxicity. Literally your brain, and more specifically, the adenosine receptors in your brain, has too much caffeine. These effects are a reversible form of neurotoxicity. Fortunately, we metabolize caffeine quickly and the undesirable effects end. By experience we have learned how to moderate our caffeine consumption to avoid the unpleasant side effects. A great deal of money is made from the neuroactive and physiological effects of caffeine. You can learn more about this fascinating drug in the chapter on caffeine. 

Proving effective reversed targeting, which results from the soft nature of this steroid, systemic levels or effects cannot be detected even after chronic ocular administration [57], Plasma levels of loteprednol etabonate and its primary metabolite (PJ-91) were less than the 1 ng/L detection limit in 10 healthy volunteers who received the drug in both eyes eight times daily for 2 days and four times daily for a further 41 days [57], In addition to its already approved uses, loteprednol etabonate is also being developed for the treatment of colitis, atopic dermatitis, and asthma based on promising results from animal studies [47, 48],... 

In terms of skin irritation and user compliance, elastic backing is more desirable. However, elastic backing materials such as polyurethane and EVA copolymer cannot be used as themselves due to their drug-permeable nature. Recently, PET/EVA laminate and PET/non-woven fabrics laminate backings are becoming popular for systemic TDS. These laminated materials are expected to add a soft feeling to the hard backing layer. 

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