Drugs

A drug is, in the broadest of terms, a chemical substance that has known biological effects on humans or other animals.^[5] Foods are generally excluded from this definition, in spite of their physiological effects on animal species.^[6][7][8]

In pharmacology, a drug is "a chemical substance used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being."^[6] Pharmaceutical drugs may be used for a limited duration, or on a regular basis for chronic disorders.^[9]

Psychoactive drugs are chemical substances that affect the function of the nervous system, altering perception, mood or consciousness.^[10] Alcohol, nicotine, and caffeine are the most widely consumed psychoactive drugs worldwide.^[11]

Recreational drugs are drugs that are not used for medicinal purposes, but are instead used for pleasure.^[12] Common recreational drugs include alcohol, nicotine and caffeine, as well as other substances such as opiates and amphetamines.

Etymology

In English, the noun "drug" is thought to originate from Old French "drogue", possibly deriving later into "droge-vate" from Middle Dutch meaning "dry barrels", referring to medicinal plants preserved in them.^[15] The transitive verb "to drug" (meaning intentionally administer a substance to someone, often without their knowledge) arose later and invokes the psychoactive rather than medicinal properties of a substance.^[16]

Medication

Nexium is a proton pump inhibitor. It is used to reduce the production of stomach acid.

Main article: pharmaceutical drug

A medication or medicine is a drug taken to cure and/or ameliorate any symptoms of an illness or medical condition, or may be used as preventive medicine that has future benefits but does not treat any existing or pre-existing diseases or symptoms.

Dispensing of medication is often regulated by governments into three categories—over-the-counter (OTC) medications, which are available in pharmacies and supermarkets without special restrictions, behind-the-counter (BTC), which are dispensed by a pharmacist without needing a doctor's prescription, and prescription only medicines (POM), which must be prescribed by a licensed medical professional, usually a physician.

In the United Kingdom, BTC medicines are called pharmacy medicines which can only be sold in registered pharmacies, by or under the supervision of a pharmacist. These medications are designated by the letter P on the label.^[17] The range of medicines available without a prescription varies from country to country.

Medications are typically produced by pharmaceutical companies and are often patented to give the developer exclusive rights to produce them. Those that are not patented (or with expired patents) are called generic drugs since they can be produced by other companies without restrictions or licenses from the patent holder.

Spiritual and religious use

This article's tone or style may not reflect the encyclopedic tone used on Wikipedia. See Wikipedia's guide to writing better articles for suggestions. (March 2015)

Main article: Entheogen

Flowering San Pedro, a psychotropic cactus that has been used for over 3,000 years.^[18] Today the vast majority of extracted mescaline is from columnar cacti, not vulnerable peyote.^[19]

The spiritual and religious use of drugs has been occurring since the dawn of our species. Drugs that are considered to have spiritual or religious use are called entheogens. Some religions are based completely on the use of certain drugs. Entheogens are mostly hallucinogens, being either psychedelics or deliriants, but some are also stimulants and sedatives.

Self-improvement

This article's tone or style may not reflect the encyclopedic tone used on Wikipedia. See Wikipedia's guide to writing better articles for suggestions. (March 2015)

Main article: Nootropic

Nootropics, also commonly referred to as "smart drugs", are drugs that are claimed to improve human cognitive abilities. Nootropics are used to improve memory, concentration, thought, mood, learning, and many other things. Some nootropics are now beginning to be used to treat certain diseases such as attention-deficit hyperactivity disorder, Parkinson's disease, and Alzheimer's disease. They are also commonly used to regain brain function lost during aging. Similarly, drugs such as steroids improve human physical capabilities and are sometimes used (legally or not) for this purpose, often by professional athletes.

Recreational drug use

Cannabis is another commonly used recreational drug.^[20]

Main article: Recreational drug use

Further information: Prohibition of drugs

Recreational drugs use is the use of a drug (legal, controlled, or illegal) with the primary intention of altering the state of consciousness through alteration of the central nervous system in order to create positive emotions and feelings.

Some national laws prohibit the use of different recreational drugs, and medicinal drugs that have the potential for recreational use are often heavily regulated. On the other hand, there are many recreational drugs that are legal in many jurisdictions and widely culturally accepted. There may be an age restriction on the consumption and purchase of legal recreational drugs. Some recreational drugs that are legal and accepted in many places include alcohol, tobacco, betel nut, and caffeine products, and in some areas of the world the legal use of drugs such as khat is common.

Administering drugs

Drugs, both medicinal and recreational, can be administered in a number of ways, or routes. Many drugs can be administered via more than one route.

• Bolus is the administration of a medication, drug or other compound that is given to raise its concentration in blood to an effective level. The administration can be given intravenously, by intramuscular, intrathecal or subcutaneous injection.
• Inhaled, (breathed into the lungs), as an aerosol or dry powder. (This includes smoking a substance)
• Injected as a solution, suspension or emulsion either: intramuscular, intravenous, intraperitoneal, intraosseous.
• Insufflation, or snorted into the nose.
• Orally, as a liquid or solid, that is absorbed through the intestines.
• Rectally as a suppository, that is absorbed by the rectum or colon.
• Sublingually, diffusing into the blood through tissues under the tongue.
• Topically, usually as a cream or ointment. A drug administered in this manner may be given to act locally or systemically.^[21]
• Vaginally as a suppository, primarily to treat vaginal infections.

Some drugs can cause addiction and habituation ^[13] and all drugs can cause side effects.^[14] Many drugs are illegal for recreational purposes and international treaties such as the Single Convention on Narcotic Drugs exist for the purpose of legally prohibiting certain substances.

Drug development

New chemical entity development[edit]

Regulation of therapeutic goods in the United States
Prescription drugs Over-the-counter drugs
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Broadly, the process of drug development can be divided into pre-clinical and clinical work.

Pre-clinical[edit]

New chemical entities (NCEs, also known as new molecular entities or NMEs) are compounds which emerge from the process of drug discovery. These will have promising activity against a particular biological target thought to be important in disease; however, little will be known about the safety, toxicity, pharmacokinetics andmetabolism of this NCE in humans. It is the function of drug development to assess all of these parameters prior to human clinical trials. A further major objective of drug development is to make a recommendation of the dose and schedule to be used the first time an NCE is used in a human clinical trial ("first-in-man" [FIM] or First Human Dose [FHD]).

In addition, drug development is required to establish the physicochemical properties of the NCE: its chemical makeup, stability, solubility. The process by which the chemical is made will be optimized so that from being made at the bench on a milligram scale by a medicinal chemist, it can be manufactured on the kilogram and then on the ton scale. It will be further examined for its suitability to be made into capsules, tablets, aerosol, intramuscular injectable, subcutaneous injectable, or intravenous formulations. Together these processes are known in preclinical development as Chemistry, Manufacturing and Control (CMC).

Many aspects of drug development are focused on satisfying the regulatory requirements of drug licensing authorities. These generally constitute a number of tests designed to determine the major toxicities of a novel compound prior to first use in man. It is a legal requirement that an assessment of major organ toxicity be performed (effects on the heart and lungs, brain, kidney, liver and digestive system), as well as effects on other parts of the body that might be affected by the drug (e.g. the skin if the new drug is to be delivered through the skin). While, increasingly, these tests can be made using in vitro methods (e.g. with isolated cells), many tests can only be made by using experimental animals, since it is only in an intact organism that the complex interplay of metabolism and drug exposure on toxicity can be examined.

The information is gathered from this pre-clinical testing, as well as information on CMC, and submitted to regulatory authorities (in the US, to the FDA), as an Investigational New Drug application or IND. If the IND is approved, development moves to the clinical phase.

Clinical phase[edit]

Clinical trials involves three or four steps:^[1]

• Phase I trials, usually in healthy volunteers, determine safety and dosing.
• Phase II trials are used to get an initial reading of efficacy and further explore safety in small numbers of sick patients.
• Phase III trials are large, pivotal trials to determine safety and efficacy in sufficiently large numbers of patients.
• Phase IV trials are post-approval trials that are sometimes a condition attached by the FDA, also called post-market surveillance studies.

The process of drug development doesn't stop once an NCE begins human clinical trials. In addition to the tests required to move a novel drug into the clinic for the first time it is also important to ensure that long-term or chronic toxicities are determined, as well as effects on systems not previously monitored (fertility, reproduction, immune system, etc.). The compound will also be tested for its capability to cause cancer (carcinogenicity testing).

If a compound emerges from these tests with an acceptable toxicity and safety profile, and it can further be demonstrated to have the desired effect in clinical trials, then it can be submitted for marketing approval in the various countries where it will be sold. In the US, this process is called a New Drug Application or NDA. Most NCEs, however, fail during drug development, either because they have some unacceptable toxicity, or because they simply do not work in clinical trials.

Cost[edit]

The full cost of bringing a new drug (i.e. a drug that is a new chemical entity) to market – from discovery through clinical trials to approval – is complex and controversial; typically it is hundreds of millions or billions of U.S. dollars. One element of the complexity is that the much-publicized final numbers often do not include just the simple out-of-pocket expenses, but also include "capital costs", which are included to take into account the long time period (often at least ten years) during which the out-of-pocket costs are expended; additionally it is often not stated whether a given figure includes the capitalized cost or comprises only out-of-pocket expenses. Another element of complexity is that all estimates are based on confidential information owned by drug companies, released by them voluntarily. There is currently no way to validate these numbers. The numbers are controversial, as drug companies use them to justify the prices of their drugs and various advocates for lower drug prices have challenged them. The controversy is not only between "high" and "low" – the numbers also vary greatly at the high end.

A study published by Steve Paul et al. in 2010 in Nature Reviews: Drug Discovery compares many of the studies, provides both capitalized and out-of-pocket costs for each, and lays out the assumptions each makes: see Supplemental Box 2.^[2] The authors offer their own estimate of the capitalized cost as being ~$1.8B, with out-of-pocket costs of ~$870M.

Studies published by diMasi et al. in 2003, report an average pre-tax, capitalized cost of approximately $800 million to bring one of the drugs from the study to market. Also, this $800 million figure includes opportunity costs of $400 million.^[3] A study published in 2006 estimates that costs vary from around $500 million to $2 billion depending on the therapy or the developing firm.^[4] A study published in 2010 in the journal Health Economics, including an author from the US Federal Trade Commission, was critical of the methods used by diMasi et al. but came up with a higher estimate of ~$1.2 billion.^[5]

Valuation[edit]

The nature of a drug development project is characterised by high attrition rates, large capital expenditures, and long timelines. This makes the valuation of such projects and companies a challenging task. Not all valuation methods can cope with these particularities. The most commonly used valuation methods are risk-adjusted net present value (rNPV), decision trees,real options, or comparables.

The most important value drivers are the cost of capital or discount rate that is used, phase attributes such as duration, success rates, and costs, and the forecasted sales, including cost of goods and marketing and sales expenses. Less objective aspects like quality of the management or novelty of the technology should be reflected in the cash flows estimation.^[6][7]

Success rate[edit]

Candidates for a new drug to treat a disease might theoretically include from 5,000 to 10,000 chemical compounds. On average about 250 of these will show sufficient promise for further evaluation using laboratory tests, mice and other test animals. Typically, about ten of these will qualify for tests on humans.^[8] A study conducted by the Tufts Center for the Study of Drug Development covering the 1980s and 1990s found that only 21.5 percent of drugs that start phase I trials are eventually approved for marketing.^[9] The high failure rates associated with pharmaceutical development are referred to as the "attrition rate" problem. Careful decision making during drug development is essential to avoid costly failures.^[10] In many cases, intelligent programme and clinical trial design can prevent false negative results. Well designed dose-finding studies and comparisons against both a placebo and a gold-standard treatment arm play a major role in achieving reliable data.^[11]

Novel initiatives to boost drug development[edit]

Novel initiatives include partnering between governmental organizations and industry. The world's largest such initiative is the Innovative Medicines Initiative (IMI), and examples of major national initiatives are Top Institute Pharma in the Netherlands and Biopeople in Denmark. In 2004, the FDA created the “Critical Path Initiative” (CPI) project to guide the new drug development process

Drug discovery

In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered.

Historically, drugs were discovered through identifying the active ingredient from traditional remedies or by serendipitous discovery. Later chemical libraries of synthetic small molecules, natural products or extracts were screened in intact cells or whole organisms to identify substances that have a desirable therapeutic effect in a process known as classical pharmacology. Since sequencing of the human genome which allowed rapid cloning and synthesis of large quantities of purified proteins, it has become common practice to use high throughput screening of large compounds libraries against isolated biological targets which are hypothesized to be disease modifying in a process known as reverse pharmacology. Hits from these screens are then tested in cells and then in animals for efficacy.

Modern drug discovery involves the identification of screening hits, medicinal chemistry and optimization of those hits to increase the affinity, selectivity (to reduce the potential of side effects), efficacy/potency, metabolic stability (to increase the half-life), and oral bioavailability. Once a compound that fulfills all of these requirements has been identified, it will begin the process of drug development prior to clinical trials. One or more of these steps may, but not necessarily, involve computer-aided drug design. Modern drug discovery is thus usually a capital-intensive process that involves large investments by pharmaceutical industry corporations as well as national governments (who provide grants and loan guarantees). Despite advances in technology and understanding of biological systems, drug discovery is still a lengthy, "expensive, difficult, and inefficient process" with low rate of new therapeutic discovery.^[1] In 2010, the research and development cost of each new molecular entity (NME) was approximately US$1.8 billion.^[2] Drug discovery is done by pharmaceutical companies, with research assistance from universities. The "final product" of drug discovery is a patent on the potential drug. The drug requires very expensive Phase I, II and III clinical trials, and most of them fail. Small companies have a critical role, often then selling the rights to larger companies that have the resources to run the clinical trials.

Discovering drugs that may be a commercial success, or a public health success, involves a complex interaction between investors, industry, academia, patent laws, regulatory exclusivity, marketing and the need to balance secrecy with communication.^[3] Meanwhile, for disorders whose rarity means that no large commercial success or public health effect can be expected, the orphan drug funding process ensures that people who experience those disorders can have some hope of pharmacotherapeutic advances.

Historical background[edit]

The idea that the effect of a drug in the human body is mediated by specific interactions of the drug molecule with biological macromolecules, (proteins or nucleic acids in most cases) led scientists to the conclusion that individual chemicals are required for the biological activity of the drug. This made for the beginning of the modern era in pharmacology, as pure chemicals, instead of crude extracts, became the standard drugs. Examples of drug compounds isolated from crude preparations are morphine, the active agent in opium, and digoxin, a heart stimulant originating from Digitalis lanata. Organic chemistry also led to the synthesis of many of the natural products isolated from biological sources.

Historically substances, whether crude extracts or purified chemicals were screened for biological activity without knowledge of the biological target. Only after an active substance was identified was an effort made to identify the target. This approach is known as classical pharmacology, forward pharmacology,^[4] or phenotypic drug discovery.^[5]

Later, small molecules were synthesized to specifically target a known physiological/pathological pathway, rather than adopt the mass screening of banks of stored compounds. This led to great success, such as the work of Gertrude Elion and George H. Hitchings on purine metabolism,^[6][7] the work of James Black^[8] on beta blockers and cimetidine, and the discovery ofstatins by Akira Endo.^[9] Another champion of the approach of developing chemical analogues of known active substances was Sir David Jack at Allen and Hanbury's, later Glaxo, who pioneered the first inhaled selective beta2-adrenergic agonist for asthma, the first inhaled steroid for asthma, ranitidine as a successor to cimetidine, and supported the development of the triptans.^[10]

Gertrude Elion, working mostly with a group of fewer than 50 people on purine analogues, contributed to the discovery of the first anti-viral; the first immunosuppressant (azathioprine) that allowed human organ transplantation; the first drug to induce remission of childhood leukaemia; pivotal anti-cancer treatments; an anti-malarial; an anti-bacterial; and a treatment for gout.

Cloning of human proteins made possible the screening of large libraries of compounds against specific targets thought to be linked to specific diseases. This approach is known as reverse pharmacology and is the most frequently used approach today.^[11]

Drug targets[edit]

The definition of "target" itself is something argued within the pharmaceutical industry. Generally, the "target" is the naturally existing cellular or molecular structure involved in the pathology of interest that the drug-in-development is meant to act on. However, the distinction between a "new" and "established" target can be made without a full understanding of just what a "target" is. This distinction is typically made by pharmaceutical companies engaged in discovery and development of therapeutics. In an estimate from 2011, 435 human genome products were identified as therapeutic drug targets of FDA-approved drugs.^[12]

"Established targets" are those for which there is a good scientific understanding, supported by a lengthy publication history, of both how the target functions in normal physiology and how it is involved in human pathology. This does not imply that the mechanism of action of drugs that are thought to act through a particular established targets is fully understood. Rather, "established" relates directly to the amount of background information available on a target, in particular functional information. The more such information is available, the less investment is (generally) required to develop a therapeutic directed against the target. The process of gathering such functional information is called "target validation" in pharmaceutical industry parlance. Established targets also include those that the pharmaceutical industry has had experience mounting drug discovery campaigns against in the past; such a history provides information on the chemical feasibility of developing a small molecular therapeutic against the target and can provide licensing opportunities and freedom-to-operate indicators with respect to small-molecule therapeutic candidates.

In general, "new targets" are all those targets that are not "established targets" but which have been or are the subject of drug discovery campaigns. These typically include newly discovered proteins, or proteins whose function has now become clear as a result of basic scientific research.

The majority of targets currently selected for drug discovery efforts are proteins. Two classes predominate: G-protein-coupled receptors (or GPCRs) and protein kinases.

Screening and design[edit]

The process of finding a new drug against a chosen target for a particular disease usually involves high-throughput screening (HTS), wherein large libraries of chemicals are tested for their ability to modify the target. For example, if the target is a novel GPCR, compounds will be screened for their ability to inhibit or stimulate that receptor (see antagonist and agonist): if the target is a protein kinase, the chemicals will be tested for their ability to inhibit that kinase.

Another important function of HTS is to show how selective the compounds are for the chosen target. The ideal is to find a molecule which will interfere with only the chosen target, but not other, related targets. To this end, other screening runs will be made to see whether the "hits" against the chosen target will interfere with other related targets - this is the process of cross-screening. Cross-screening is important, because the more unrelated targets a compound hits, the more likely that off-target toxicity will occur with that compound once it reaches the clinic.

It is very unlikely that a perfect drug candidate will emerge from these early screening runs. It is more often observed that several compounds are found to have some degree of activity, and if these compounds share common chemical features, one or more pharmacophores can then be developed. At this point, medicinal chemists will attempt to use structure-activity relationships (SAR) to improve certain features of the lead compound:

• increase activity against the chosen target
• reduce activity against unrelated targets
• improve the druglikeness or ADME properties of the molecule.

This process will require several iterative screening runs, during which, it is hoped, the properties of the new molecular entities will improve, and allow the favoured compounds to go forward to in vitro and in vivo testing for activity in the disease model of choice.

Amongst the physico-chemical properties associated with drug absorption include ionization (pKa), and solubility; permeability can be determined by PAMPA and Caco-2. PAMPA is attractive as an early screen due to the low consumption of drug and the low cost compared to tests such as Caco-2, gastrointestinal tract (GIT) and Blood–brain barrier (BBB) with which there is a high correlation.

A range of parameters can be used to assess the quality of a compound, or a series of compounds, as proposed in the Lipinski's Rule of Five. Such parameters include calculated properties such as cLogP to estimate lipophilicity, molecular weight, polar surface area and measured properties, such as potency, in-vitro measurement of enzymatic clearance etc. Some descriptors such as ligand efficiency^[13] (LE) and lipophilic efficiency^[14][15] (LiPE) combine such parameters to assess druglikeness.

While HTS is a commonly used method for novel drug discovery, it is not the only method. It is often possible to start from a molecule which already has some of the desired properties. Such a molecule might be extracted from a natural product or even be a drug on the market which could be improved upon (so-called "me too" drugs). Other methods, such as virtual high throughput screening, where screening is done using computer-generated models and attempting to "dock" virtual libraries to a target, are also often used.

Another important method for drug discovery is drug design, whereby the biological and physical properties of the target are studied, and a prediction is made of the sorts of chemicals that might (e.g.) fit into an active site. One example is fragment-based lead discovery (FBLD). Novel pharmacophores can emerge very rapidly from these exercises. In general, computer-aided drug design is often but not always used to try to improve the potency and properties of new drug leads.

Once a lead compound series has been established with sufficient target potency and selectivity and favourable drug-like properties, one or two compounds will then be proposed for drug development. The best of these is generally called the lead compound, while the other will be designated as the "backup".

Nature as source of drugs[edit]

Traditionally many drugs and other chemicals with biological activity have been discovered by studying allelopathy - chemicals that organisms create that affect the activity of other organisms in the fight for survival.^[16]

Despite the rise of combinatorial chemistry as an integral part of lead discovery process, natural products still play a major role as starting material for drug discovery.^[17] A 2007 report^[18] found that of the 974 small molecule new chemical entities developed between 1981 and 2006, 63% were natural derived or semisynthetic derivatives of natural products. For certain therapy areas, such as antimicrobials, antineoplastics, antihypertensive and anti-inflammatory drugs, the numbers were higher. In many cases, these products have been used traditionally for many years.

Natural products may be useful as a source of novel chemical structures for modern techniques of development of antibacterial therapies.^[19]

Despite the implied potential, only a fraction of Earth’s living species has been tested for bioactivity.

Plant-derived[edit]

Main article: Bark isolates

Prior to Paracelsus, the vast majority of traditionally used crude drugs in Western medicine were plant-derived extracts. This has resulted in a pool of information about the potential of plant species as an important source of starting material for drug discovery. A different set of metabolites is sometimes produced in the different anatomical parts of the plant (e.g. root, leaves and flower), and botanical knowledge is crucial also for the correct identification of bioactive plant materials.

Microbial metabolites[edit]

Main articles: Streptomyces isolates and Medicinal molds

Microbes compete for living space and nutrients. To survive in these conditions, many microbes have developed abilities to prevent competing species from proliferating. Microbes are the main source of antimicrobial drugs. Streptomyces species have been a valuable source of antibiotics. The classical example of an antibiotic discovered as a defense mechanism against another microbe is the discovery of penicillin in bacterial cultures contaminated by Penicillium fungi in 1928.

Marine invertebrates[edit]

Main article: Sponge isolates

Marine environments are potential sources for new bioactive agents.^[20] Arabinose nucleosides discovered from marine invertebrates in 1950s, demonstrating for the first time that sugar moieties other than ribose and deoxyribose can yield bioactive nucleoside structures. However, it was 2004 when the first marine-derived drug was approved. The cone snail toxinziconotide, also known as Prialt, was approved by the Food and Drug Administration to treat severe neuropathic pain. Several other marine-derived agents are now in clinical trials for indications such as cancer, anti-inflammatory use and pain. One class of these agents are bryostatin-like compounds, under investigation as anti-cancer therapy.

Chemical diversity of natural products[edit]

As above mentioned, combinatorial chemistry was a key technology enabling the efficient generation of large screening libraries for the needs of high-throughput screening. However, now, after two decades of combinatorial chemistry, it has been pointed out that despite the increased efficiency in chemical synthesis, no increase in lead or drug candidates has been reached.^[18] This has led to analysis of chemical characteristics of combinatorial chemistry products, compared to existing drugs or natural products. The chemoinformatics concept chemical diversity, depicted as distribution of compounds in the chemical space based on their physicochemical characteristics, is often used to describe the difference between the combinatorial chemistry libraries and natural products. The synthetic, combinatorial library compounds seem to cover only a limited and quite uniform chemical space, whereas existing drugs and particularly natural products, exhibit much greater chemical diversity, distributing more evenly to the chemical space.^[17] The most prominent differences between natural products and compounds in combinatorial chemistry libraries is the number of chiral centers (much higher in natural compounds), structure rigidity (higher in natural compounds) and number of aromatic moieties (higher in combinatorial chemistry libraries). Other chemical differences between these two groups include the nature of heteroatoms (O and N enriched in natural products, and S and halogen atoms more often present in synthetic compounds), as well as level of non-aromatic unsaturation (higher in natural products). As both structure rigidity and chirality are both well-established factors in medicinal chemistry known to enhance compounds specificity and efficacy as a drug, it has been suggested that natural products compare favourable to today's combinatorial chemistry libraries as potential lead molecules.

Natural product drug discovery[edit]

Screening[edit]

Two main approaches exist for the finding of new bioactive chemical entities from natural sources.

The first is sometimes referred to as random collection and screening of material, but in fact the collection is often far from random in that biological (often botanical) knowledge is used about which families show promise, based on a number of factors, including past screening. This approach is based on the fact that only a small part of earth’s biodiversity has ever been tested for pharmaceutical activity. It is also based on the fact that organisms living in a species-rich environment need to evolve defensive and competitive mechanisms to survive, mechanisms which might usefully be exploited in the development of drugs that can cure diseases affecting humans. A collection of plant, animal and microbial samples from rich ecosystems can potentially give rise to novel biological activities worth exploiting in the drug development process. One example of a successful use of this strategy is the screening for antitumour agents by the National Cancer Institute, started in the 1960s. Paclitaxel was identified from Pacific yew tree Taxus brevifolia. Paclitaxel showed anti-tumour activity by a previously undescribed mechanism (stabilization of microtubules) and is now approved for clinical use for the treatment of lung, breast and ovarian cancer, as well as for Kaposi's sarcoma. Early in the 21st century, Cabazitaxel (made by Sanofi, a French firm), another relative of taxol has been shown effective against prostate cancer, also because it works by preventing the formation of microtubules, which pull the chromosomes apart in dividing cells (such as cancer cells). Still another examples are: 1. Camptotheca (Camptothecin · Topotecan · Irinotecan · Rubitecan · Belotecan); 2. Podophyllum (Etoposide · Teniposide); 3a. Anthracyclines (Aclarubicin · Daunorubicin · Doxorubicin · Epirubicin · Idarubicin · Amrubicin · Pirarubicin · Valrubicin · Zorubicin); 3b. Anthracenediones (Mitoxantrone · Pixantrone).

Nor do all drugs developed in this manner come from plants. Professor Louise Rollins-Smith of Vanderbilt University's Medical Center, for example, has developed from the skin of frogs a compound which blocks AIDS. Professor Rollins-Smith is aware of declining amphibian populations and has said: "We need to protect these species long enough for us to understand their medicinal cabinet."

The second main approach involves Ethnobotany, the study of the general use of plants in society, and ethnopharmacology, an area inside ethnobotany, which is focused specifically on medicinal uses.

Both of these two main approaches can be used in selecting starting materials for future drugs. Artemisinin, an antimalarial agent from sweet wormtree Artemisia annua, used in Chinese medicine since 200BC is one drug used as part of combination therapy for multiresistant Plasmodium falciparum.

Structural elucidation[edit]

The elucidation of the chemical structure is critical to avoid the re-discovery of a chemical agent that is already known for its structure and chemical activity. Mass spectrometry is a method in which individual compounds are identified based on their mass/charge ratio, after ionization. Chemical compounds exist in nature as mixtures, so the combination of liquid chromatography and mass spectrometry (LC-MS) is often used to separate the individual chemicals. Databases of mass spectras for known compounds are available, and can be used to assign a structure to an unknown mass spectrum. Nuclear magnetic resonance spectroscopy is the primary technique for determining chemical structures of natural products. NMR yields information about individual hydrogen and carbon atoms in the structure, allowing detailed reconstruction of the molecule’s architecture.