Vertebrate tissue extracts have also been used as medicines for thousands of years. In fact, many prescriptions containing animal products are listed in Egyptian papyrus. In recent years, the pharmacology of various extracts, particularly of endocrine organs, has been investigated. Extracts from pituitary, thyroid and adrenal glands have been shown to exhibit dramatic effects when administered to vertebrates, and the active principles of these extracts have been isolated. The chemistry and biological activity of many important endogenous constituents of endocrine organs, such as epinephrine, thyroxine, corticosterone, insulin, prostaglandins, leukotrienes, endorphins, atrial natriuretic factor, nitric oxide, and endothelin have been elucidated, and information obtained from these studies has been used as a basis for the development of many clinically useful drugs.
Natural products from marine organisms have also been shown to have marked biological effects . Didemnin B and bryostatin I are being tested for antitumor activity. Ciguatoxin is responsible for the human illness caused by the consumption of ciguateric fishes. Manoalide, which is isolated from the sponge, Luffariella variabilis is an irreversible inhibitor of phospholipase A2 and has been investigated for the treatment of various skin diseases.
Several natural products produce chemicals that are effective as ionophores . These molecules were first recognized in mitochondrial membrane-linked energy functions. Ionophores can form lipid-soluble complexes with polar cations like potassium, sodium, calcium, and magnesium, and these complexes can diffuse through cell membranes and carry these cations into the cytosol along their concentration gradient. The ionophore, monensin, selectively binds sodium ion; valinomycin and nigericin are selective for potassium ion; and calcimycin is selective for calcium ion. In contrast, lasalocid is a nonselective ionophore that transports all three ions, sodium, potassium and calcium, across membranes. Although many ionophores are too toxic to be used in humans, a new synthetic ionophore that is chemically related to calcimycin and selectively complexes with calcium is being tested as a cardiotonic drug. It is also interesting that topically applied valinomycin lowers the intraocular pressure in laboratory animals and may be useful for the treatment of glaucoma.
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