Central nervous system drugs, natural product-derived

The most remarkable property of these derivatives of microbial natural products is the wide margin of safety accorded to treated mammals - the reason being that the drug does not readily cross the blood-brain barrier to any extent (18). Fortunately in mammals, GABA mediated nerves only occur in the central nervous system. 

One of the most fascinating products containing multiple components is a combination of the natural product reserpine, hydralazine hydrochloride, and hydrochlorothiazide. This drug product is available in tablet form and contains 0.1 mg of reserpine USP, 25 mg of hydralazine hydrochloride, and 15 mg of hydrochlorothiazide (Fig. 6). Reserpine is an indole alkaloid derived from the dried root of Rauwolfia serpentina and is well known for its complex molecular architecture, the challenges faced during its total synthesis, and its profound effect on the central nervous system as an antihypertensive. Hydralazine is also an antihypertensive and hydrochlorothiazide has diuretic properties. The combination of these three very different molecular structures brings diversity to the analytical testing required. 

The study of natural products, or Nature s Combinatorial Library , has had a long history as a source of drugs, and plants have historically been at the forefront of natural product drug discovery. In the anticancer area, for example, vinblastine and vincristine, etoposide, paclitaxel (Taxol), docetaxel, topotecan, and irinotecan, among others, are all plant-derived natural products or modified versions of plant compounds, while antimalarial therapy would be much poorer without quinine and artemisinin and the drugs derived from these plant products. This chapter provides an overview of the major medicinal agents that are themselves natural products isolated from plants or are chemical modifications of such lead compounds. It covers the therapeutic areas of cancer, HIV, malaria, cardiovascular, and central nervous system (CNS) diseases. Natural plant products have also made contributions in areas such as immunomodulatory and antibiotic activities," and the reader is referred to the cited reviews for information on these areas. 

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