Shaman Pharmaceuticals: Integrating Indigenous Knowledge,
Tropical Medicinal Plants, Medicine, Modern Science and
Reciprocity into a Novel Drug Discovery Approach
Shaman Pharmaceuticals, Inc.
213 East Grand Ave.
South San Francisco, CA 94080
Tropical forest plant species have served as a source of medicines for people of the tropics for millennia. Many medical practitioners with training in pharmacology and/or pharmacognosy are well aware of the number of modern therapeutic agents that have been derived from tropical forest species. In fact, over 120 pharmaceutical products currently in use are plant-derived, and some 75% of these were discovered by examining the use of these plants in traditional medicine(1). Of these, as shown in Table I, a large portion have come from tropical forest species. Yet while many modern medicines are plant-derived, the origins of these pharmaceutical agents and their relationship to the knowledge of the indigenous people in the tropical forests is usually omitted.
Today, five centuries after the Old World and the New World first collided, it is no longer a question of whether indigenous peoples should benefit from products that have been developed on the basis of their knowledge. Individual ethnobiologists and organizations such as the Society of Economic Botany, the International Society of Ethnobiology, and the American Anthropological Association have emphatically stated the importance of ethical reciprocal conduct by all parties who perform research with indigenous peoples(2-6). The most challenging issues which remain are: How do indigenous and local peoples, themselves, define benefits, and through what mechanisms can individuals and organizations working with these groups provide such benefits? These are questions which one pioneering pharmaceutical company, Shaman Pharmaceuticals, addresses as part of its ethical obligation of doing business.
Shaman Pharmaceuticals, Inc. is a South San Francisco-based pharmaceutical company that focuses on isolating bioactive compounds from tropical plants that have a history of medicinal use. Shaman is working to promote the conservation of tropical forests and bridge the gap between the biomedical needs of both indigenous cultures and the rest of the global population. Eschewing the mass screening approach typically done by many pharmaceutical companies, Shaman has pioneered a novel approach to drug discovery, integrating traditional plant natural products chemistry, the science of ethnobotany, medicine, and medicinal chemistry while maintaining a commitment of reciprocity to the indigenous cultures.
The Rainforest as a Source For New Pharmaceuticals
Until the early 1970's, there was a strong interest in looking at plants as sources of new pharmaceutical agents. In fact, many modern pharmaceutical companies can trace their origins to products originating from plants. However, advances in molecular biology, genetic engineering, and computational chemistry in the late 1970's and 1980's and, even more recently, advances in combinatorial chemistry(7,8) created much promise within the pharmaceutical industry without the need to explore nature's chemical diversity.
Natural product chemists and phytochemists recognize that plant species contain a bewildering diversity of secondary metabolites. Individual plant species often contain over 1,000 unique chemical entities (or the enzymatic machinery needed to produce compounds upon the proper stimulus). One of the most compelling explanations for this vast array of chemical diversity, which resides within the biological diversity of tropical plant species, is the science of chemical ecology. Plants living in tropical forest habitats have had to develop and survive under intense competition for resources and nutrients. They have also had to develop an extraordinary array of defenses, most of them chemical, to protect themselves from viral diseases, fungal pathogens, insects and mammalian predators. The biodiversity of tropical forest plant species, coupled with the chemical diversity found within each plant, leads one to the conclusion that tropical plants are perhaps the most valuable source of new bioactive chemical entities.
The enormous chemical diversity of the tropical rain forest can be best appreciated if one considers the relative abundance and diversity of plants on earth. It is estimated that there are roughly 500,000 higher flowering plant species occupying terrestrial habitats. Of these 500,000 species, many await discovery description by scientists. A large number of species has only been very superficially examined for their pharmacological and medical application. Less than 1% of these species has been thoroughly investigated for their potential use as novel therapeutic agents.
The development of robotics for high-throughput, random screening in the 1980's and an ability to handle large numbers of samples, coupled with the need to find new bioactive chemical entities has renewed interest in looking once again at novel tropical plant species, and has stimulated a long overdue renaissance of activities in the areas of plant natural product chemistry, pharmacognosy, and ethnomedical research. One approach that this renewed interest in plant natural product chemistry has taken involves a return to the classic random collection of plants that are incorporated into high throughput screening programs with a variety of mechanism-based assays with specific applications to numerous therapeutic areas. This methodology is well-suited to the infrastructure and philosophical approach to drug discovery of traditional yet highly successful pharmaceutical firms.
A more integrated approach involves a highly-focused collective program for medicinal plants with a primary emphasis on the use of plants by indigenous people in the tropical regions of the world. This latter methodology is the one utilized by Shaman Pharmaceuticals since its inception, and the approach has been highly effective. As depicted in Figure 1, the ethnomedically driven approach to drug discovery differs from other drug discovery processes by beginning and ending in humans.
Shaman relies extensively and intensively on the primary fieldwork of internationally recognized ethnobotanists who work closely with their indigenous colleagues and shamans (traditional doctors in cultures) in tropical regions of Asia, Africa and Latin America. This approach requires a great deal of research well before any plant material is collected and brought into the company for investigation, and involves examining all the known information regarding the use of plants by people in any given tropical forest habitats to treat a variety of illnesses. Before any research expedition is undertaken, we prepare a full regional study on the epidemiology, traditional medicine, culture and ecology of the people and the environment in which they live. Information on the plants known to be utilized in any given area is assembled by searching several international databases on ethnomedicine, medicinal activities of plants and any known chemistry of plants with such activity. We also search for data from international and national hospitals in remote areas and treatment programs that work with local and native people. All of this information is synthesized and integrated into our field research program.
Shaman Pharmaceutical's field research teams are then sent to selected tropical regions to collect indigenous information and witness first-hand the use of plant medicines to treat various illnesses. These field research teams are comprised of ethnobotanists, western trained medical doctors, local botanical collaborators and indigenous healers and herbalists. This combination of expertise allows for a highly focused selection of plant candidates for screening and subsequent development.
Since all of the tropical plant species collected by Shaman have a history of ethnomedical use in humans (Figure 1), the need to screen tens of thousands of plant species and plant species extracts is unnecessary. In essence, the rainforest, its associated ethnomedical history, and the field research prioritization serves as the initial biological screen. Instead, the in vivo laboratory screening serves as a confirmatory screen. The most promising plant leads are then subjected to fractionation campaigns, whereby natural product chemists use state-of-the-art chemical separation techniques to separate the chemical entity responsible for the observed activity from its inactive components. Modern spectroscopic techniques are then used to elucidate the chemical structure of the active compound.
Shaman Pharmaceutical's operations began in 1990. Utilizing the ethnobotanical/ethnomedical approach to collecting tropical medicinal plant species, Shaman has been successful in bringing two products into clinical trials within 24 months of that time. This focused approach (Figure 1) is currently being used in Shaman's antidiabetic discovery program. Since the inception of the diabetes program two years ago, Shaman has discovered multiple new chemical leads from plant sources and, to date, patents have been filed on five of them. Each of these chemical leads is currently undergoing preclinical evaluation.
The Rainforest as a Source For Medicinal Chemistry Leads
Three years ago, Shaman decided to augment its drug discovery effort using medicinal chemistry. One of medicinal chemistry's missions is to provide synthetic support for natural product leads in the event that the isolated natural product is available in a low yield and/or the plant source is not amenable to sustainable harvesting. In this situation, when feasible, a synthetic approach to the natural product is considered. An equally important medicinal chemistry mission is to use the isolated natural product as a template for further structural modification to reduce toxicity and/or improve potency. As a result of this process, new chemical leads can be generated from the initial orally active natural product lead. The medicinal chemistry program has been highly successful: Two total syntheses originating from an antifungal natural product isolated from Irlbachia alata and Anthocleista djalonensis were completed and have been published,(9,10) and a structural modification study originating from a natural product isolated from Ambrosia chamissonis resulted in four patents and has recently been published.(11) More recently in the antidiabetic discovery area, the advantage of the Shaman Pharmaceutical process -- beginning with an orally active natural product lead as the template -- has led, through further synthetic modification, to the discovery of two new orally active synthetic leads. A patent has been filed on one of these with the second patent soon to follow, and both are currently undergoing preclinical evaluation.
Shaman's Reciprocity Strategies
The idea of compensating indigenous people for the use of knowledge about biological diversity is one based on fairness and equity. A logical means of compensating indigenous peoples for their role in a drug discovery process would be to accord them a share of the profits from the drug, once it is commercialized. However, because of the long period of time needed for commercial drug discovery and development, often ten years or more, such a mechanism for reciprocity requires a long waiting period before any benefit is realized by the indigenous peoples. Furthermore, in most instances, the indigenous knowledge gathered would not lead to a commercial product and thus, no benefit of any kind would come to the local people.
From its inception, Shaman has been committed to the concept of reciprocal benefits: to developing new therapeutic agents by working with indigenous and local peoples of the tropical rainforests and, in the process, contributing to the conservation of biological and cultural diversity, or "biocultural diversity".(12-14) The kind and type of reciprocity is driven by the expressed needs of the people themselves. We place a high value on the knowledge that we receive from our collaborators, and for this reason, feel it absolutely necessary to reciprocate the contribution to our drug development process. Inherent in our commitment is a direct acknowledgment, in both ethical and financial terms, of the intellectual property rights of the indigenous people with whom we work. In our opinion, their traditional knowledge is an irreplaceable cultural resource. Thus, we believe that our company has the dual obligation to provide compensation for that knowledge and to help our collaborators maintain it.
The needs of the indigenous people with whom we work are often immediate. Shaman considers it unacceptable to delay compensation to the indigenous peoples until a product is developed and generating a profit on the market. Our approach to appropriate reciprocity was developed in part to address the needs of the indigenous peoples and to address a potential conflict between our company's recognized obligations and the nature of the pharmaceutical industry. Thus, Shaman's approach to reciprocity instead involves three timeframes -- immediate, medium-term, and long-term. A number of articles describing specific aspects of our biocultural diversity and reciprocity programs has been published, and those interested should consult these articles.(15,16) Here, only a brief overview of our reciprocity program is offered.
Short-term reciprocity can take many forms, but the underlying theme is that it addresses the immediate needs of the community. While short-term reciprocity is a novel concept amongst the pharmaceutical industry, it really is quite simple. We ask the local people with whom we collaborate to identify compensation options. Some examples of short-term compensation have included building an airstrip extension in the Ecuadorian Amazon, organizing community-based public health workshops and forest conservation workshops, and offering direct medical care to our partner communities. One example of the latter involved a request by the Yanomami Indians in the Northern Brazilian Amazon. Their people were dying from a chloroquinine-resistant strain of malaria which was introduced by the gold miners. Shaman subsequently contacted Hoffman LaRoche, Inc., the manufacturer of Lariam, a synthetic compound which is effective against chloroquinine-resistant malaria. Hoffman LaRoche responded with a donation of Lariam. We forwarded the medication to the Commission for the Creation of a Yanomami Preserve in São Paulo, which delivered it to the Yanomami for use among the most critical cases. A second example involved a Papua New Guinea collaborator who had been poked in the eye with a thorn while doing his field botanical work six months prior to our visit. Subsequently, the man had developed a cataract which made him blind. Upon our medical evaluation of this man, we determined that his sight could be restored with routine cataract surgery and an intraocular lens implant. Since this man did not have the money to pay for the surgery, Shaman paid for all of his surgery and travel fees. Shaman has also provided and completed two clean drinking water systems to communities in Ecuador and Indonesia.
Medium-term reciprocity focuses on providing benefits that may not be immediately apparent, but that will nonetheless provide benefit to the community before profit sharing might. One method used is to enhance the communities scientific and research capability. Specific examples of this have included providing chemical reagents, high pressure liquid chromatography equipment, scientific software, books, and other resources used for training the local country scientists. Another method used has been to provide scholarships and fellowships to scientists working on traditional medicine. Shaman also has an ongoing exchange program, whereby local scientists have come to Shaman for a period of 1-9 months to learn new scientific technology. Another form of medium-term reciprocity has included the commissioning of sustainable harvesting studies of plant species that are important for local traditional medicine and also are of interest to Shaman.
The long-term reciprocity involves returning a portion of the profits to the indigenous communities once a commercial product is realized. However, Shaman does not advocate only compensating the community or communities directly responsible for the commercial product. Instead, Shaman will provide a portion of the profits of any and all products to all of the communities and countries in which we have worked.
An important aspect of this long-term strategy is the mechanism that will be used to distribute the compensation. At the same time that Shaman was incorporated as a for-profit company, it founded the Healing Forest Conservancy as a nonprofit organization with an independent board of directors and advisors. The Healing Forest Conservancy is dedicated to conserve cultural and biological diversity and to sustain the development and management of the natural and biocultural resources that are a part of the heritage of native populations. The Conservancy was founded because no governmental organization existed to provide a formal and consistent process to compensate countries and communities for ethnobotanical leads which subsequently are developed into commercial product. The Conservancy ensures a mechanism for the species-rich tropical countries and the small-scale indigenous communities in tropical forests to be equitably compensated for their participation in the development of therapeutic agents. A number of pilot programs have been initiated and described in recent publications.(14,17,18)
It is a fact that the tropical rainforest regions of the world are disappearing due to a multitude of commercial interests. With this destruction comes the loss of cultural habitat and indigenous knowledge which has been gained and utilized for millennia. As part of our drug discovery effort, we work with indigenous cultures to provide alternative income-generating activities, such as sustainable harvesting and extraction industries, to large-scale logging or clearing of the land for livestock.(14) Such sustainable harvesting activities can contribute to the conservation of the biological and cultural diversity of the region. Our novel reciprocity programs demonstrate the value we place on indigenous knowledge. To preserve the rainforest without preservation of shamanic knowledge of the plants in the forest would be to cut ourselves off from the cures for present and future diseases. In order to preserve that knowledge, we must ensure that it is passed on from generation to generation by promoting cultural diversity. In contrast to most pharmaceutical drug discovery efforts, Shaman has developed a pioneering technology platform, integrating the sciences of ethnobotany, ethnomedicine, medicine, modern separation science, medicinal chemistry, and primary in vivo screening. The process has led to the discovery of multiple orally active antihyperglycemic leads in our diabetes drug discovery program that are currently undergoing preclinical evaluation. We are currently entering Phase II clinical trials with ProvirTM, an oral product for the treatment of secretory diarrhea, beginning a pivotal Phase III clinical study on Virend®, a topical antiviral for the treatment of herpes, and plan to file in 1996 an Investigational New Drug application (IND) to begin Phase I testing on Nikkomycin Z, an oral antifungal for the treatment of endemic mycoses.
The authors would like to acknowledge the contributions of Lisa Conte, Shaman's Scientific Strategy Team, outside investigators and the entire research, development and administration teams of Shaman Pharmaceuticals. Special thanks are due to all of the indigenous and local scientists with whom we work in the tropics of Asia, Africa and Latin America, especially Coweña, Huepe, Coba, Tiro, Coba and César Gualinga.
(1) Farnsworth, N. R.; Akerele, O.; Bingel, A. S. Bull. World Health Org., 1985, 63, 965-981.
(2) Anon. The Manila Declaration Concerning the Ethical Utilization of Asian Biological Resources. UNESCO Regional Network for the Chemistry of Natural Products in Southeast Asia, Selangor, Malaysia: 1992.
(3) Boom, B. Ethics in Ethnopharmacology. In Proceedings of the First Congress of Ethnobiology; Elizabetsky, E., ed.; Museu Paraense Emilio Goeldi: Belem, Brazil, 1990; Vol. 2, Part F, 147-153.
(4) Boom, B. Garden, 1990, 14, 28-31.
(5) Cunningham, A. B. Cultural Survival Quarterly (summer), 1991, 15, 1-4.
(6) Cox, P. A.; Balick, M. J. Scientific American, 1994, 270, 82-87.
(7) Borman, S. Chemical & Engineering News, February 12, 1996, 74(7), 29-54.
(8) Baum, R. Chemical & Engineering News, February 12, 1996, 74(7), 28, and references cited therein.
(9) Bierer, D. E.; Dubenko, L. G.; Gerber, R. E.; Litvak, J.; Chu, J.; Thai, D. L.; Tempesta, M. S.; Truong, T. V. J. Org. Chem., 1995, 60, 7646.
(10) Bierer, D. E.; Gerber, R. E.; Jolad, S. D.; Ubillas, R. P.; Randle, J.; Nauka, E.; LaTour, J.; Dener, J. M.; Fort, D. M.; Kuo, J. E.; Inman, W. D.; Dubenko, L. G.; Ayala, F.; Ozioko, A.; Obialor, C.; Elisabetsky, E.; Carlson, T.; Truong, T. V.; Bruening, R. C. J. Org. Chem., 1995, 60, 7022.
(11) Bierer, D. E.; Dener, J. M.; Dubenko, L. G.; Gerber, R. E.; Litvak, J.; Peterli, S.; Peterli-Roth, P.; Truong, T. V.; Mao, G.; Bauer, B. E. J. Med. Chem., 1995, 38, 2628.
(12) King, S. R. Cultural Survival Quarterly, 1991, 15(3), 19-22.
(13) King, S. R. Conservation and Tropical Medicinal Plant Research. In Medicinal Resources of the Tropical Forest; Balick, M. J.; Elisabetsky, E.; Laird, S. A., eds.; Columbia University Press: New York, 1996; pp 63-74.
(14) Moran, K. Ethnobiology and US Policy. In Sustainable Harvest and Marketing of Rainforest Products, Plotkin, M. Famolare, L., eds.; Island Press: Washington, D. C., 1992; Chapter 5.
(15) King, S. R.; Carlson, T. J. Intersciencia, 1995, 20 (3), 134-139.
(16) King, S. R.; Carlson, T. J.; Moran, K. Biological Diversity, Indigenous Knowledge, Drug Discovery, and Intellectual Property Rights. In Valuing Local Knowledge: Indigenous People and Intellectual Property Rights; Brush, S.; Stabinsky, D., eds.: Island Press: Washington, D. C., 1996; Chapter 8, pp 167-185.
(17) Moran, K. Biocultural Diversity Conservation Through the Healing Forest Conservancy. In Intellectual Property Rights for Indigenous Peoples, A Source Book; Greaves, T., ed.; Society for Applied Anthropology: Oklahoma City, OK, 1994; pp 101-109.
(18) King, S. R.; Carlson, T. J.; Moran, K. J. Ethnopharm., 1996, 51, 45-57.
About the Authors
Dr. Donald E Bierer is Group Leader of Medicinal Chemistry for Shaman Pharmaceuticals, Inc. Previously, Dr. Bierer was a scientist with Procter & Gamble Pharmaceuticals in Norwich, NY, and prior to that, was a postdoctoral research associate with Professor Henry Rapoport at the University of California, Berkeley. He received his Ph.D. in organic chemistry in 1988 from the University of Tennessee and his B.S. degree in chemistry and pre-law from Indiana University of Pennsylvania. Address: Shaman Pharmaceuticals, Inc. 213 East Grand Ave. South San Francisco, CA 94080; fax: 415-873-8377; e-mail: email@example.com
Dr. Thomas J. Carlson is Senior Director of Ethnobotanical Field Research for Shaman Pharmaceuticals, Inc. Dr. Carlson develops and coordinates the medical and public health components of the ethnobotanical expeditions at Shaman Pharmaceuticals, is a medical advisor to the Healing Forest Conservancy and is also an Assistant Clinical Professor at Stanford University Medical Center. He received his M.D. degree at Michigan State University and received his B.S and M.S. degrees in botany from the University of Michigan. Address: Shaman Pharmaceuticals, Inc. 213 East Grand Ave. South San Francisco, CA 94080; fax: 415-873-8367; e-mail: firstname.lastname@example.org
Dr. Steven R. King is Senior Vice-President for Ethnobotany and Conservation for Shaman Pharmaceuticals, Inc. Formerly the chief botanist for Latin America at Arlington Virginia's Nature Conservancy, Dr. King has also worked as a research associate for the Committee on Managing Global Genetic Resources at the National Academy of Sciences, and was a doctoral fellow at The New York Botanical Garden's Institute of Economic Botany. His Ph.D. and M.S. degrees were earned from City University of New York, and his research experience covers such countries as Papua New Guinea, Paraguay, Indonesia, Mexico, Columbia, Ecuador, Peru, Bolivia, and Guatemala. Dr. King helped found Shaman Pharmaceuticals in 1990. Address: Shaman Pharmaceuticals, Inc. 213 East Grand Ave. South San Francisco, CA 94080; fax: 415-873-8367; e-mail: email@example.com
CLINICALLY USEFUL DRUGS FROM TROPICAL RAIN FOREST PLANTS
|Compound Name||Plant Source||Therapeutic Category|
|in Medical Sciences|
|Ajmalicine||Rauvolfia serpentina (L.) Benth. ex Kurz||Circulatory stimulant|
|(Apocynaceae) (Indian snakeroot)|
|Andrographolide||Andrographis paniculata Nees (Acanthaceae)||Antibacterial|
|Arecoline||Areca catechu L. (Palmae) (Betek-nut palm)||Anthelmintic|
|Asiaticoside||Centella asiatica (L.) Urban||Vulnerary|
|(Umbelliferae) (Indian pennywort)|
|*Atropine||Duboisia myoporoides R.Br. (Solanaceae)||Anticholinergic|
|(Australian cork tree)|
|*Bromelain||Ananas comosus (L.) Merrill (Bromeliaceae)||Antiinflammatory;|
|*Camphor||Cinnamomum camphora (L.) Nees & Eberm.||Rubefacient|
|(Lauraceae) (Camphor tree)|
|*Chymopapain||Carica papaya L. (Caricaceae) (Papaya)||Proteolytic;|
|*Cocaine||Erythroxylum coca Lam. (Erythroxylaceae)||Local anesthetic|
|Curcumin||Curcuma longa L. (Zingiberaceae) (Turmeric)||Choleretic|
|*Deserpidine||Rauvolfia tetraphylla L. (Apocynaceae)||Antihypertensive;|
|*L-Dopaa||Mucuna deeringiana (Bort.) Merrill||Antiparkinsonism|
|(Leguminosae) (Velvet Bean)|
|*Emetine||Cephaelis ipecacuanha (Brot.) A. Richard||Amebicide;|
|Glaucarubin||Simarouba glauca DC. (Simaroubaceae)||Amebicide|
|Glaziovine||Ocotea glaziovii Mez (lauraceae)||Antidepressant|
|Gossypol||Gossypium spp. (Malvaceae) (Cotton)||Male contraceptive|
|*Hyoscyamine||Duboisia Myoporoides R.Br. (Solanaceae)||Anticholinergic|
|(Australian cork tree)|
|Kawaina||Piper methysticum Forst. f. (Piperaceae)||Tranquilizer|
|Monocrotaline||Crotalaria spectabilis Roth (Leguminosae)||Antitumor agent|
|Neoandrographolide||Andrographis paniculata Nees (Acanthaceae)||Dysentery|
|Nicotine||Nicotiana tabacum L. (Solanaceae)||Insecticide|
|*Ouabain||Strophanthus gratus (Hook.) Baill.||Cardiotonic|
|(Apocynaceae) (Twisted flower)|
|*Papain||Carica papaya L. (Caricaceae) (Papaya)||Proteolytic; Mucolytic|
|*Physostigmine||Physostigma venenosum Balf. (Leguminosae)||Anticholinesterase|
|Picrotoxin||Anamirta cocculus (L.) Wright & Arn.||Analeptic|
|*Pilocarpine||Pilocarpus jaborandi Holmes (Rutaceae)||Parasympathomimetic|
|*Quinidine||Cinchona ledgeriana Moens ex Trimen||Antiarrhytmic|
|(Rubiaceae) (Yellow cinchona)|
|*Quinine||Cinchona ledgeriana Moens ex Trimen||Antimalarial;|
|(Rubiaceae) (Yellow cinchona)||Antipyretic|
|Quisqualic acid||Quisqualis indica L. (Combretaceae)||Anthelminthic|
|*Rescinnami||Rauvolfia serpentina (L.) Benth. ex Kurz||Anthypertensive;|
|(Apocynaceae) (Indian snakeroot)||Tranquilizer|
|*Reserpine||Rauvolfia serpentina (L.) Benth. ex Kurz||Antihypertensive;|
|(Apocynaceae) (Indian snakeroot)||Tranquilizer|
|Rorifone||Rorippa indica (L.) Hiern (Cruciferae)||Antitussive|
|Rotenone||Lonchocarpus nicou (Aubl.) DC.||Piscicide|
|(Leguminosae) (Cube root)|
|*Scopolamine||Datura metel L. (Solanaceae)||Sedative|
|Stevioside||Stevia rebaudiana Hemsley (Compositae)||Sweetener|
|(Sweet herb; Ka'a He'e)|
|Strychnine||Strychnos nux-vomica L. Loganiaceae||CNS stimulant|
|Theobromine||Theobroma cacao L. (Sterculiaceae)||Diuretic; Vasodilator|
|*Tubocurarine||Chondrodendron tomentosum R. & P.||Skeletal muscle|
|Vasicine (Peganine)||Adhatoda vasica Nees (Acanthaceae)||Oxytocic|
|*Vinblastine||Catharanthus roseus (L.) G.Don||Antitumor agent|
|(Apocynaceae) (Madagascan periwinkle)|
|Yohimbine||Pausinystalia yohimba (K.Schum.) Pierre||Adrenergic blocker;|
|ex Beille (Rubiaceae)||Aphrodisiac|
(1) Farnsworth, N. R Screening Plants for New Medicines. In Biodiversity; Wilson, E. O., ed.; National Academy Press: Washington, D. C., 1988; pp 83-97.
(2) Soejarto, D. D.; Farnsworth, N. R. Perspect. Biol. Med., 1989, 32, 244-256.
* Currently used in the United States.
a Now also synthesized commercially.
A Comparison of Shaman's Ethnomedically Driven Drug Discovery Process with the Traditional Mass Screening Drug Discovery Approach.
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