Saturday, August 2, 2008

Visible & UV Spectroscopy
Visible and Ultraviolet Spectroscopy
1. Background
An obvious difference between certain compounds is their color. Thus, quinone is yellow; chlorophyll is green; the 2,4-dinitrophenylhydrazone derivatives of aldehydes and ketones range in color from bright yellow to deep red, depending on double bond conjugation; and aspirin is colorless. In this respect the human eye is functioning as a spectrometer analyzing the light reflected from the surface of a solid or passing through a liquid. Although we see sunlight (or white light) as uniform or homogeneous in color, it is actually composed of a broad range of radiation wavelengths in the ultraviolet (UV), visible and infrared (IR) portions of the spectrum. As shown on the right, the component colors of the visible portion can be separated by passing sunlight through a prism, which acts to bend the light in differing degrees according to wavelength. Electromagnetic radiation such as visible light is commonly treated as a wave phenomenon, characterized by a wavelength or frequency. Wavelength is defined on the left below, as the distance between adjacent peaks (or troughs), and may be designated in meters, centimeters or nanometers (10-9 meters). Frequency is the number of wave cycles that travel past a fixed point per unit of time, and is usually given in cycles per second, or hertz (Hz). Visible wavelengths cover a range from approximately 400 to 800 nm. The longest visible wavelength is red and the shortest is violet. Other common colors of the spectrum, in order of decreasing wavelength, may be remembered by the mnemonic: ROY G BIV. The wavelengths of what we perceive as particular colors in the visible portion of the spectrum are displayed and listed below. In horizontal diagrams, such as the one on the bottom left, wavelength will increase on moving from left to right.
Violet: 400 - 420 nm
Indigo: 420 - 440 nm
Blue: 440 - 490 nm
Green: 490 - 570 nm
Yellow: 570 - 585 nm
Orange: 585 - 620 nm
Red: 620 - 780 nm
When white light passes through or is reflected by a colored substance, a characteristic portion of the mixed wavelengths is absorbed. The remaining light will then assume the complementary color to the wavelength(s) absorbed. This relationship is demonstrated by the color wheel shown on the right. Here, complementary colors are diametrically opposite each other. Thus, absorption of 420-430 nm light renders a substance yellow, and absorption of 500-520 nm light makes it red. Green is unique in that it can be created by absoption close to 400 nm as well as absorption near 800 nm.Early humans valued colored pigments, and used them for decorative purposes. Many of these were inorganic minerals, but several important organic dyes were also known. These included the crimson pigment, kermesic acid, the blue dye, indigo, and the yellow saffron pigment, crocetin. A rare dibromo-indigo derivative, punicin, was used to color the robes of the royal and wealthy. The deep orange hydrocarbon carotene is widely distributed in plants, but is not sufficiently stable to be used as permanent pigment, other than for food coloring. A common feature of all these colored compounds, displayed below, is a system of extensively conjugated pi-electrons.

2. The Electromagnetic Spectrum
The visible spectrum constitutes but a small part of the total radiation spectrum. Most of the radiation that surrounds us cannot be seen, but can be detected by dedicated sensing instruments. This electromagnetic spectrum ranges from very short wavelengths (including gamma and x-rays) to very long wavelengths (including microwaves and broadcast radio waves). The following chart displays many of the important regions of this spectrum, and demonstrates the inverse relationship between wavelength and frequency (shown in the top equation below the chart).
The energy associated with a given segment of the spectrum is proportional to its frequency. The bottom equation describes this relationship, which provides the energy carried by a photon of a given wavelength of radiation.
To obtain specific frequency, wavelength and energy values use this calculator.

3. UV-Visible Absorption Spectra
To understand why some compounds are colored and others are not, and to determine the relationship of conjugation to color, we must make accurate measurements of light absorption at different wavelengths in and near the visible part of the spectrum. Commercial optical spectrometers enable such experiments to be conducted with ease, and usually survey both the near ultraviolet and visible portions of the spectrum.

The visible region of the spectrum comprises photon energies of 36 to 72 kcal/mole, and the near ultraviolet region, out to 200 nm, extends this energy range to 143 kcal/mole. Ultraviolet radiation having wavelengths less than 200 nm is difficult to handle, and is seldom used as a routine tool for structural analysis.
The energies noted above are sufficient to promote or excite a molecular electron to a higher energy orbital. Consequently, absorption spectroscopy carried out in this region is sometimes called "electronic spectroscopy". A diagram showing the various kinds of electronic excitation that may occur in organic molecules is shown on the left. Of the six transitions outlined, only the two lowest energy ones (left-most, colored blue) are achieved by the energies available in the 200 to 800 nm spectrum. As a rule, energetically favored electron promotion will be from the highest occupied molecular orbital (HOMO) to the lowest unoccupied molecular orbital (LUMO), and the resulting species is called an excited state. When sample molecules are exposed to light having an energy that matches a possible electronic transition within the molecule, some of the light energy will be absorbed as the electron is promoted to a higher energy orbital. An optical spectrometer records the wavelengths at which absorption occurs, together with the degree of absorption at each wavelength. The resulting spectrum is presented as a graph of absorbance (A) versus wavelength, as in the isoprene spectrum shown below. Since isoprene is colorless, it does not absorb in the visible part of the spectrum and this region is not displayed on the graph. Absorbance usually ranges from 0 (no absorption) to 2 (99% absorption), and is precisely defined in context with spectrometer operation.
Because the absorbance of a sample will be proportional to the number of absorbing molecules in the spectrometer light beam (e.g. their molar concentration in the sample tube), it is necessary to correct the absorbance value for this and other operational factors if the spectra of different compounds are to be compared in a meaningful way. The corrected absorption value is called "molar absorptivity", and is particularly useful when comparing the spectra of different compounds and determining the relative strength of light absorbing functions (chromophores). Molar absorptivity (ε) is defined as:
Molar Absorptivity, ε = A / c l

(where A= absorbance, c = sample concentration in moles/liter & l = length of light path through the sample in cm.)
If the isoprene spectrum on the right was obtained from a dilute hexane solution (c = 4 * 10-5 moles per liter) in a 1 cm sample cuvette, a simple calculation using the above formula indicates a molar absorptivity of 20,000 at the maximum absorption wavelength. Indeed the entire vertical absorbance scale may be changed to a molar absorptivity scale once this information about the sample is in hand. Clicking on the spectrum will display this change in units.
Chromophore
Example
Excitation
λmax, nm
ε
Solvent
C=C
Ethene
π __> π*
171
15,000
hexane
C≡C
1-Hexyne
π __> π*
180
10,000
hexane
C=O
Ethanal
n __> π*π __> π*
290180
1510,000
hexanehexane
N=O
Nitromethane
n __> π*π __> π*
275200
175,000
ethanolethanol
C-X X=Br X=I
Methyl bromideMethyl Iodide
n __> σ*n __> σ*
205255
200360
hexanehexane


From the chart above it should be clear that the only molecular moieties likely to absorb light in the 200 to 800 nm region are pi-electron functions and hetero atoms having non-bonding valence-shell electron pairs. Such light absorbing groups are referred to as chromophores. A list of some simple chromophores and their light absorption characteristics is provided on the left above. The oxygen non-bonding electrons in alcohols and ethers do not give rise to absorption above 160 nm. Consequently, pure alcohol and ether solvents may be used for spectroscopic studies.The presence of chromophores in a molecule is best documented by UV-Visible spectroscopy, but the failure of most instruments to provide absorption data for wavelengths below 200 nm makes the detection of isolated chromophores problematic. Fortunately, conjugation generally moves the absorption maxima to longer wavelengths, as in the case of isoprene, so conjugation becomes the major structural feature identified by this technique.Molar absorptivities may be very large for strongly absorbing chromophores (>10,000) and very small if absorption is weak (10 to 100). The magnitude ofε reflects both the size of the chromophore and the probability that light of a given wavelength will be absorbed when it strikes the chromophore.


4. The Importance of Conjugation
A comparison of the absorption spectrum of 1-pentene, λmax = 178 nm, with that of isoprene (above) clearly demonstrates the importance of chromophore conjugation. Further evidence of this effect is shown below. The spectrum on the left illustrates that conjugation of double and triple bonds also shifts the absorption maximum to longer wavelengths. From the polyene spectra displayed in the center diagram, it is clear that each additional double bond in the conjugated pi-electron system shifts the absorption maximum about 30 nm in the same direction. Also, the molar absorptivity (ε) roughly doubles with each new conjugated double bond. Spectroscopists use the terms defined in the table on the right when describing shifts in absorption. Thus, extending conjugation generally results in bathochromic and hyperchromic shifts in absorption.The appearance of several absorption peaks or shoulders for a given chromophore is common for highly conjugated systems, and is often solvent dependent. This fine structure reflects not only the different conformations such systems may assume, but also electronic transitions between the different vibrational energy levels possible for each electronic state. Vibrational fine structure of this kind is most pronounced in vapor phase spectra, and is increasingly broadened and obscured in solution as the solvent is changed from hexane to methanol.

Terminology for Absorption Shifts
Nature of Shift
Descriptive Term
To Longer Wavelength
Bathochromic
To Shorter Wavelength
Hypsochromic
To Greater Absorbance
Hyperchromic
To Lower Absorbance
Hypochromic

To understand why conjugation should cause bathochromic shifts in the absorption maxima of chromophores, we need to look at the relative energy levels of the pi-orbitals. When two double bonds are conjugated, the four p-atomic orbitals combine to generate four pi-molecular orbitals (two are bonding and two are antibonding). This in the section concerning diene chemistry. In a similar manner, the three double bonds of a conjugated triene create six pi-molecular orbitals, half bonding and half antibonding. The energetically most favorable π __> π* excitation occurs from the highest energy bonding pi-orbital (HOMO) to the lowest energy antibonding pi-orbital (LUMO). The following diagram illustrates this excitation for an isolated double bond (only two pi-orbitals) and, on clicking the diagram, for a conjugated diene and triene. In each case the HOMO is colored blue and the LUMO is colored magenta. Increased conjugation brings the HOMO and LUMO orbitals closer together. The energy (ΔE) required to effect the electron promotion is therefore less, and the wavelength that provides this energy is increased correspondingly (remember λ = h • c/ΔE ).

Examples of π __> π* ExcitationClick on the Diagram to Advance

Many other kinds of conjugated pi-electron systems act as chromophores and absorb light in the 200 to 800 nm region. These include unsaturated aldehydes and ketones and aromatic ring compounds. A few examples are displayed below. The spectrum of the unsaturated ketone (on the left) illustrates the advantage of a logarithmic display of molar absorptivity. The π __> π* absorption located at 242 nm is very strong, with an ε = 18,000. The weak n __> π* absorption near 300 nm has an ε = 100.

Benzene exhibits very strong light absorption near 180 nm (ε > 65,000) , weaker absorption at 200 nm (ε = 8,000) and a group of much weaker bands at 254 nm (ε = 240). Only the last group of absorptions are completely displayed because of the 200 nm cut-off characteristic of most spectrophotometers. The added conjugation in naphthalene, anthracene and tetracene causes bathochromic shifts of these absorption bands, as displayed in the chart on the left below. All the absorptions do not shift by the same amount, so for anthracene (green shaded box) and tetracene (blue shaded box) the weak absorption is obscured by stronger bands that have experienced a greater red shift. As might be expected from their spectra, naphthalene and anthracene are colorless, but tetracene is orange.

The spectrum of the bicyclic diene (above right) shows some vibrational fine structure, but in general is similar in appearance to that of isoprene, Closer inspection discloses that the absorption maximum of the more highly substituted diene has moved to a longer wavelength by about 15 nm. This "substituent effect" is general for dienes and trienes, and is even more pronounced for enone chromophores.

PHARMACOGNOCY

PHARMACOGNOCY
The word "pharmacognosy" derives from the
Greek words pharmakon (drug), and gnosis or "knowledge". The term pharmacognosy was used for the first time by the Austrian physician Schmidt in 1811. Originally - during the 19th century and the beginning of the 20th century - "pharmacognosy" was used to define the branch of medicine or commodity sciences ("Warenkunde" in German) which dealt with drugs in their crude, or unprepared, form. Crude drugs are the dried, unprepared material of plant, animal or mineral origin, used for medicine. The study of pharmakognosie was first developed in German-speaking areas of Europe. The term drogenkunde ("science of crude drugs") is also used synonymously.
Although most pharmacognostic studies focus on plants and medicines derived from plants, other types of organisms are also regarded as pharmacognostically interesting, in particular, various types of microbes (bacteria, fungi, etc.), and, recently, various marine organisms.
Pharmacognosy is interdisciplinary, drawing on a broad spectrum of biological and socio-scientific subjects, including
botany, ethnobotany, medical anthropology, marine biology, microbiology, herbal medicine, chemistry (phytochemistry), pharmacology, pharmaceutics, clinical pharmacy and pharmacy practice. The contemporary study of pharmacognosy can be divided into the fields of
medical
ethnobotany: the study of the traditional use of plants for medicinal purposes;
ethnopharmacology: the study of the pharmacological qualities of traditional medicinal substances;
the study of
phytotherapy (the medicinal use of plant extracts); and
phytochemistry, the study of chemicals derived from plants (including the identification of new drug candidates derived from plant sources).
Ethnopharmacology
When studying the effectiveness of herbal medicines and other nature-derived remedies, the information of the traditional uses of certain extracts of even extract combinations plays a key role. The lack of studies proving the use of herbs in traditional care is especially an issue in the United States where the use of herbal medicine has fallen out of use since the Second World War and was considered suspect since the
Flexner Report of 1910 led to the closing of the eclectic medical schools where botanical medicine was exclusively practiced. This is further complicated by most herbal studies in the latter part of the 20th Century having been published in languages other than English such as German, Dutch, Chinese, Japanese, Korean and Persian. As it may be more difficult to review foreign language publications, many of these publications have undergone been incorporated into the US Food and Drug Administration's "FDA" determinations of drug safety. In 1994 the US Congress passed the Dietary Supplement Health and Education Act (DSHEA), regulating labeling and sales of herbs and other supplements. Most of the 2000 US companies making herbal or natural products choose to market their products as food supplements that do not require substantial testing.
Issues in Phytotherapy
The part of pharmacognosy focusing on use of crude extracts or semi-pure mixtures originating from nature, namely phytotherapy, is probably the best known and also the most debated area in pharmacognosy. Although phytotherapy is sometimes connected to
alternative medicine, when critically conducted, it may be considered the scientific study on the effects and clinical use of herbal medicines.
Constituents and Drug Synergyism
One characteristic of crude drug material is that constituents may have an opposite, moderating or enhancing effect. Hence, the final effect of any crude drug material will be a product of the interactions between the constituents and the effect of each constituent on its own. To effectively study the existence and affect of such interactions, scientific studies must examine the affect that multiple constituents, given concurrently, have on the system. Herbalists assert that as phytopharmaceuticals rely upon
synergy for their activities, plants with high levels of active constituents like ginsenosides or hypericin may not correlate with the strength of the herbs. In phytopharmaceutical or herbal medicine, the therapeutic effects of herbs cannot be determined unless its active ingredient or cofactors are identified or the herb is adminsistered as a whole. One way manufacturers have attempted to indicate strength is to engage in standardization to a marker compound. Companies use different markers, or different levels of the same markers, or different methods of testing for marker compounds. Many herbalists believe that the active ingredient in a plant is the plant itself.
Herb and Drug Interactions
The Sloan Kettering Memorial Cancer Center stated, in a review of a Juice product, which had been marketed as preventing cancer, that antioxidants could theoretically interfere with chemotherapy. A recent review of the effect of antioxidants on chemotherapy, however, found no evidence for any deleterious effects of antioxidants on chemotherapy. A study of herb drug interactions indicated that the vast majority of drug interactions occurred in four classes of drugs, the chief class being blood thinners, but also including
protease inhibitors, cardiac glycosides and certain antibiotics like cyclosporin.Cyclosporin is not an antibiotic it is an immuno-suppressant
The major herbs that have caused interactions include St. Johns Wort, which will counteract immunosupressive drugs and interfere with digoxin and protease inhibitors. A complete list can be found at: The constituents of garlic, peppermint and milk thistle have been shown to have effects on the CYP3A4 enzymes in vitro, but it is not clear whether these constituents will have the same effect in vivo (humans).
Natural products chemistry
Most bioactive compounds of natural origin are secondary metabolites, i.e. species-specific chemical agents that can be grouped into various categories. A typical protocol to isolate a pure chemical agent from natural origin is bioassay-guided fractionation, meaning step-by-step separation of extracted components based on differences in their physicochemical properties, and assessing the biological activity, followed by next round of separation and assaying. Typically, such work is initiated after a given crude drug formulation (typically prepared by solvent extraction of the natural material) is deemed "active" in a particular in vitro assay. If the end-goal of the work at hand is to identify which one(s) of the scores or hundreds of compounds are responsible for the observed in vitro activity, the path to that end is fairly straightforward: 1. fractionate the crude extract, e.g. by solvent partitioning or chromatography. 2. test the fractions thereby generated with in vitro assay. 3. repeat steps 1) and 2) until pure, active compounds are obtained. 4. determine structure(s) of active compound(s), typically by using spectroscopic methods. It should be stressed here that in vitro activity does not necessarily translate to activity in humans or other living systems. The most common means for fractionation are solvent-solvent partitioning and chromatographic techniques such as
high-performance liquid chromatography (HPLC), medium-pressure liquid chromatography, "flash" chromatography, open-column chromatography, vacuum-liquid chromatography (VLC), thin-layer chromatography (TLC), with each technique being most appropriate for a given amount of starting material. Countercurrent chromatography (CCC) is particularly well-suited for bioassay-guided fractionation because, as an all-liquid separation technique, concern about irreversible loss or denaturation of active sample components is minimized. After isolation of a pure substance, the task of elucidating its chemical structure can be addressed. For this purpose, the most powerful methodologies available are nuclear magnetic resonance spectroscopy (NMR) and mass spectroscopy (MS)[citation needed]. In the case of drug discovery efforts, structure elucidation of all components that are active in vitro is typically the end goal. In the case of phytotherapy research, the investigator may use in vitro BAGF as a tool to identify pharmacologically interesting or important components of the crude drug. The work does not stop after structural identification of in vitro actives, however. The task of "dissecting and reassembling" the crude drug one active component at a time, in order to achieve a mechanistic understanding of how it works in phytotherapy, is quite daunting. This is because it is simply too difficult, from cost, time, regulatory, and even scientific perspectives, to study experimental fractions of the crude drug in humans. In vitro assays are therefore used to identify chemical components of the crude drug that may rationally be expected to have a given pharmacological effect in humans, and to provide a rational basis for standardization of a crude drug formulation to be tested in [and sold/marketed to] humans.
Loss of Biodiversity
Farnsworth for example, has found that 25% of all prescriptions dispensed from community pharmacies in the United States from l959 to l980 contained active ingredients extracted from higher plants. A much higher percentage is found in the developing world. As many as 80% of all people living in developing countries, or roughly two thirds of the world's population, rely almost exclusively on traditional medicines using natural substances, mostly derived from plants.
Constituents of substances used by traditional healers, have been incorporated into modern medicine.
Quinine, physostigmine, d-tubocurarine, pilocarpine and ephedrine, have been demonstrated to have active effects. Knowledge of traditional medicinal practices is fast disappearing, particularly in the Amazon, as native healers die out and are replaced by more modern medical practitioners. Botanists and pharmacologists are racing to learn these ancient practiceswhich, like the forest plants they employ, are also endangered
A explanation for some species loss is habitat lost due to
invasive species introduction. Herbalist David Winston has suggested that a high proportion of nonnative species seen as invasive (kudzu, Japanese knotweed, mimosa, lonicera, St. Johnswort and purple loosestrife) may be harvested for the domestic herbal medicine market.
Species extinction is not only due to habitat loss. Overharvesting of medicinal species of plants and animals also contributes to species loss. This is particularly notable in the matter of
Traditional Chinese Medicine where crude drugs of plant and animal origin are used with increasing demand. People with a stake in TCM often seek chemical and biological alternatives to endangered species because they realize that plants and animals lost from the wild are also lost to medicine forever but different cultural attitudes bedevil conservation effortsStill conservation is not a new idea: Chinese advice against overexploitation of natural medicinal species dates from at least Mencius, a philosopher living in the 4th century BC.
Cooperation between western conservationists and practitioners have been beset by cultural difficulties. Westerners may emphasise urgency in matters of conservation, while Chinese may wish for the products used in TCM to remain publicly available. One repeated fallacyis that
rhinoceros horn is used as an aphrodisiac in TCM. It is, in fact, prescribed for fevers and convulsions by TCM practitioners. There are no peer-reviewed studies showing that this treatment is effective. In 1995 representatives of the oriental medicine communities in Asia met with conservationists at a symposium in Hong Kong, organized by TRAFFIC. The two groups established a clear willingness to cooperate through dialogue and mutual understanding. This has led to several meetings, including the 1997 First International Symposium on Endangered Species Used in Traditional East Asian Medicine where China was among 136 nations to sign a formal resolution recognizing that the uncontrolled use of wild species in traditional medicine threatens their survival and the continuation of these medical practices. The resolution, drawn up by the UN Convention on International Trade in Endangered Species (CITES), aims to initiate new partnerships in conservation.
Sustainable Sources of Plant and Animal Drugs
As species face loss of habitat or overharvesting, there have been new issues to deal with in sourcing crude drugs. These include changes to the herb from farming practices, substitution of species or other plants altogether, adulteration and cross-pollination issues. For instance, ginseng which is field farmed may have significant problems with fungus, making contamination with fungicides an issue. This may be remedied with woods grown programs, but they are insufficient to produce enough ginseng to meet demand. The wildcrafted echinacea, black cohosh and American ginseng often rely upon old growth root, often in excess of 50 years of age and it is not clear that younger stock will have the same pharmaceutical effect. Black cohosh may be adulterated with the related Chinese actea species, which is not the same. Ginseng may be replaced by ginseniodes from Jiaogulan which has been stated to have a different effect than the full panax root.
The problem may be exacerbated by the growth of pills and capsules as the preferred method of ingesting medication as they are cheaper and more available than traditional, individually tailored prescriptions of raw medicinals but the contents are harder to track. Seahorses are a case in point: Seahorses once had to be of a certain size and quality before they were accepted by practitioners and consumers. But declining availability of the preferred large, pale and smooth seahorses has been offset by the shift towards prepackaged medicines, which make it possible for TCM merchants to sell previously unused juvenile, spiny and dark-coloured animals. Today almost a third of the seahorses sold in China are prepackaged.
The farming of plant or animal species, used for medicinal purposes has caused difficulties. Rob Parry Jones and Amanda Vincent write:
One solution is to farm medicinal animals and plants. Chinese officials have promoted this as a way of guaranteeing supplies as well as protecting endangered species. And there have been some successes—notably with plant species, such as American ginseng—which is used as a general tonic and for chronic coughs. Red deer, too, have for centuries been farmed for their antlers, which are used to treat impotence and general fatigue. But growing your own is not a universal panacea. Some plants grow so slowly that cultivation in not economically viable. Animals such as musk deer may be difficult to farm, and so generate little profit.
Seahorses are difficult to feed and plagued by disease in captivity. Other species cannot be cultivated at all. Even when it works, farming usually fails to match the scale of demand. Overall, cultivated TCM plants in China supply less than 20 per cent of the required 1.6 million tonnes per annum. Similarly, China's demand for animal products such as musk and pangolin scales far exceeds supply from captive-bred sources.
Farming alone can never resolve conservation concerns, as government authorities and those who use Chinese medicine realise. For a start, consumers often prefer ingredients taken from the wild, believing them to be more potent. This is reflected in the price, with wild oriental ginseng fetching up to 32 times as much as cultivated plants. Then there are welfare concerns. Bear farming in
China is particularly controversial. Around 7600 captive bears have their bile "milked" through tubes inserted into their gall bladders. The World Society for the Protection of Animals states that bear farming is surrounded by "appalling levels of cruelty and neglect" . Chinese officials state that 10 000 wild bears would need to be killed each year to produce as much bile, making bear farming the more desirable option. The World society for the Protection of Animals, however, states that "it is commonly believed in China that the bile from a wild bear is the most potent, and so farming bears for their bile cannot replace the demand for the product extracted from wild animals".
One alternative to farming involves replacing medical ingredients from threatened species with manufactured chemical compounds. In general, this sort of substitution is difficult to achieve because the active ingredient is often not known. In addition, most TCM users believe that TCM compounds may act synergistically so several ingredients may interact to give the required effect. Thus TCM users often people prefer the wild source.
Tauro ursodeoxycholic acid, the active ingredient of bear bile, can be synthesised and is used by some Western doctors to treat gallstones, but many TCM consumers reject it as being inferior to the natural substance from wild animals.

PLANT DRUGS

PLANT DRUGS
Drugs are generally classified by effect but this is often difficult and results in ambiguity. Many drugs can produce more than one effect, depending on the quantity taken.1. Behavior stimulants - cocaine caffeine, nicotine.2. Convulsant - strychnine3. Narcotic analgesics - opium, morphine, codeine4. Psychedelics - THC, mescaline, atropine, scopolamine, LSD5. Antipsychotic agents - resperine6. Sedatives and hypnotic compounds - alcoholMost psychoactive compounds contain nitrogen and most are alkaloids. THC, alcohol, LSD and hallucinogenic terpenes are exceptions.MODE OF ACTION1. Absorption - orally, injection, membrane absorption.2. Most act on CNS, drugs reach brain faster than other tissues but passage of chemicals into brain tissue is more difficult than in other parts of body.3. Alter interactions between neurons. Neurons transmist information chemically via neurotransmitters which can cross the synapse between neurons. Sites in the receptor neuron recognize compound and bind with it, which causes a response in receptor. Psychoactive drugs alter or mimic neurotransmitters: acetylcholine, norepinephrine, serotonin, neuropeptides, dopamine, and anandamine. Check the text for a more detailed description.DRUG USAGE1. Drug usage in human cultures is very ancient and was often associated with religious and cultural ceremonies and customs.2. Reasons for drug usage in modern society are complex and difficult to understand but main difference is that usage is usually not associated with religious and cultural events unless you count rock concerts.MarijuanaCannabis sativa - cultivated for 10,000 years, source of fiber, food and oil. One of most widely used nonmedical drugs. May be 2nd most important cash crop in U.S. and #1 in California. Native to central Asia. Indians were first culture to exploit hallucinogenic properties. Discovered that active component is richest in upper leaves and bracts of female plants. Removal of males from population prevents fertilization and seed production which produces sinsemilla - most potent form. Is consumed in milk in India (bhang). Hashish is the resin - very potent.Smoking of marijuana was introduced by the Dutch. Use of marijuana in Europe was introduced by French artists and writers. Production of Cannabis was introduced in U.S. in 18th century for hemp, use as a drug first occurred in 1800's, first artists, then general use. Federal government used legends of violence associated with marijuana use to help pass 1937 Marijuana Tax Law, which taxed but did not prohibit marijuana. Use in U.S. exploded in 1960's, largely due to Vietnam War.Medical uses - relief of glaucoma, nausea caused by chemotherapy.Effects - heavy users suffer lung damage similar to cigarette smokers, general stupidity.OpiumPapaver somniferum - used for 5000 years. Arabs introduced opium to China in 7th century. Opium addiction became a problem so Chinese officials outlawed it. England traded opium to China for goods even though it was illegal in their own country and in China. China and England fought two wars over the English import of opium, China lost both, ceded Hong Kong to British at end of first war. Use of opium in China did not drop until Communist Revolution in 1949. Most opium is currently grown in SE Asia.Morphine is purified from opium and is a very potent painkiller. Many Civil War soldiers became addicted to morphine.Heroin is a derivative of morphine, is even more potent and addicting. Heroin is illegal in U.S., even for medicinal purposes.CocaineErythroxylum coca - native to Andes, used at least 3000 years, natives of the region chew on leaves to relieve hunger and work at high elevations. Cocaine was isolated in 1860. Freud recommended it as a treatment for alcoholism and morphine addiction. Coca cola contained coca extracts (still does but cocaine has been removed). Many early "remedies" contained caffeine, alcohol and cocaine. Cocaine was declared illegal in U.S. in 1914. Cocaine is expensive and a status symbol - "rich man's drug" and was not widely used until introduction of crack cocaine, which is much cheaper, potent and addictive.PeyoteLophophora williamsii - Cactus native to Rio Grande Valley, mescaline is active compound and is present in "buttons" - stem tips. Causes nausea, then hallucinations. Is illegal except for members of the Native American Church.LSDIpomoea tricolor - Morning glory. Seeds contain LSD, very dangerous since seeds are toxic. Synthetic form of LSD is 10X as potent as natural form.Tropane AlkaloidsFound in members of Solanaceae: Datura, Hyoscyamus, Atropa belladonna, Mandragona officinarum.Datura - rich in scopolamine, hallucinogenic and very toxicAtropine - "flying ointment", absorbed through skin, associated with legend of witches flying on broomsticks, werewolf legends.TobaccoSolanum nicotianum - stimulant of CNS, addictive, carcinogenic, causes heart and lung disease, miscarriages, infant health disorders.

Plant Based Drugs and Medicines

Plant Based Drugs and Medicines
By Leslie Taylor, NDOctober 13, 2000
Today there are at least 120 distinct chemical substances derived from plants that are considered as important drugs currently in use in one or more countries in the world. These chemical substances are shown in the table below. Several of the drugs sold today are simple synthetic modifications or copies of the naturally obtained substances. The original plant substance/chemical name is shown under the "Drug" column rather than the finished patented drug name. For example, many years ago a plant chemical was discovered in a tropical plant, Cephaelis ipecacuanha, and the chemical was named emetine. A drug was developed from this plant chemical called Ipecac which was used for many years to induce vomiting mostly if someone accidently swallowed a poisonous or harmful substance. Ipecac can still be found in pharmacies in many third world countries but has been mostly replaced by other drugs in the United States. Another example of this is the plant chemical named taxol shown in the drug column below. The name taxol is the name of the plant chemical orginally discovered in the plant. A pharmaceutical company copied this chemical and patented a drug named Paclitaxel™ which is used in various types of tumors today in the U.S. and many other countries.
The 120 substances shown below are sold as drugs worldwide but not in all countries. Some European countries regulate herbal sustances and products differently than in the United States. Many European countries, including Germany, regulate herbal products as drugs and pharmaceutical companies prepare plant based drugs simply by extracting out the active chemicals from the plants. A good example is the plant substance/drug shown below, cynarin. Cynarin is a plant chemical found in the common artichoke (Cynara scolymus). In Germany, a cynarin drug is sold for liver problems and hypertension which is simply this one chemical extracted from the artichoke plant or a plant extract which has been standardized to contain a specific milligram amount of this one chemical. These products are manufactured by pharmaceutical companies, sold in pharmacies in Germany and a doctor's prescription is required to purchase them. In the United States artichoke extracts are available as natural products and sold in health food stores. Some products are even standardized to contain a specific amount of the cynarin chemical. You can purchase these natural and standardized extracts over the counter without a prescription and you could not go to a pharmacy in the U.S. and obtain a cynarin drug with a prescription. Another similar example is the plant chemical, silymarin, shown in the drug column below. Silymarin is a chemical found in the milk thistle plant and natural milk thistle extracts standarized to contain specific amounts of silymarin are found in just about every health food store in the United States. However in Germany, silymarin drugs and milk thistle standardized extracts are sold only in pharmacies and require a doctor's prescription for liver problems.
Some of the drug/chemicals shown below are still sold as plant based drugs requiring the processing of the actual plant material. Others have been chemically copied or synthesized by laboratories and no plant materials are used in the manufacture of the drug. A good example of this is the plant chemical quinine, which was discovered in a rainforest tree (Cinchona ledgeriana) over 100 years ago. For many years the quinine chemical was extracted from the bark of this tree and processed into pills to treat malaria. Then a scientist was able to synthesize or copy this plant alkaloid into a chemical drug without using the original tree bark for manufacturing the drug. Today, all quinine drugs sold are manufactured chemically without the use of any tree bark. However, another chemical in the tree called quinidine which was found to be useful for various heart conditions couldn't be completely copied in the laboratory and the tree bark is still harvested and used to extract this plant chemical from it. Quinidine extracted from the bark is still used today to produce quinidine-based drugs. In the U.S. there are four patented brand-name heart drugs sold in pharmacies containing bark-extracted quinidine: Cardioquin™, Quinaglute Dura-tabs™, Quinidex Extentabs™ and Quin-Release™.
The following table below will help you begin your research on drugs made from plants. We don't have the time or resources to provide a full comprehensive list of all patented drug names and herbal drugs sold in other countries. The chemical/drug names and plant names will give you enough to start on to continue your research on important plant based drugs and medicines.

Drug/Chemical
Action/Clinical Use
Plant Source
Acetyldigoxin
Cardiotonic
Digitalis lanata
Adoniside
Cardiotonic
Adonis vernalis
Aescin
Anti-inflammatory
Aesculus hippocastanum
Aesculetin
Anti-dysentery
Frazinus rhychophylla
Agrimophol
Anthelmintic
Agrimonia supatoria
Ajmalicine
Circulatory Disorders
Rauvolfia sepentina
Allantoin
Vulnerary
Several plants
Allyl isothiocyanate
Rubefacient
Brassica nigra
Anabesine
Skeletal muscle relaxant
Anabasis sphylla
Andrographolide
Baccillary dysentery
Andrographis paniculata
Anisodamine
Anticholinergic
Anisodus tanguticus
Anisodine
Anticholinergic
Anisodus tanguticus
Arecoline
Anthelmintic
Areca catechu
Asiaticoside
Vulnerary
Centella asiatica
Atropine
Anticholinergic
Atropa belladonna
Benzyl benzoate
Scabicide
Several plants
Berberine
Bacillary dysentery
Berberis vulgaris
Bergenin
Antitussive
Ardisia japonica
Betulinic acid
Anticancerous
Betula alba
Borneol
Antipyretic, analgesic, antiinflammatory
Several plants
Bromelain
Anti-inflammatory, proteolytic
Ananas comosus
Caffeine
CNS stimulant
Camellia sinensis
Camphor
Rubefacient
Cinnamomum camphora
Camptothecin
Anticancerous
Camptotheca acuminata
(+)-Catechin
Haemostatic
Potentilla fragarioides
Chymopapain
Proteolytic, mucolytic
Carica papaya
Cissampeline
Skeletal muscle relaxant
Cissampelos pareira
Cocaine
Local anaesthetic
Erythroxylum coca
Codeine
Analgesic, antitussive
Papaver somniferum
Colchiceine amide
Antitumor agent
Colchicum autumnale
Colchicine
Antitumor agent, anti-gout
Colchicum autumnale
Convallatoxin
Cardiotonic
Convallaria majalis
Curcumin
Choleretic
Curcuma longa
Cynarin
Choleretic
Cynara scolymus
Danthron
Laxative
Cassia species
Demecolcine
Antitumor agent
Colchicum autumnale
Deserpidine
Antihypertensive, tranquillizer
Rauvolfia canescens
Deslanoside
Cardiotonic
Digitalis lanata
L-Dopa
Anti-parkinsonism
Mucuna sp
Digitalin
Cardiotonic
Digitalis purpurea
Digitoxin
Cardiotonic
Digitalis purpurea
Digoxin
Cardiotonic
Digitalis purpurea
Emetine
Amoebicide, emetic
Cephaelis ipecacuanha
Ephedrine
Sympathomimetic, antihistamine
Ephedra sinica
Etoposide
Antitumor agent
Podophyllum peltatum
Galanthamine
Cholinesterase inhibitor
Lycoris squamigera
Gitalin
Cardiotonic
Digitalis purpurea
Glaucarubin
Amoebicide
Simarouba glauca
Glaucine
Antitussive
Glaucium flavum
Glasiovine
Antidepressant
Octea glaziovii
Glycyrrhizin
Sweetener, Addison's disease
Glycyrrhiza glabra
Gossypol
Male contraceptive
Gossypium species
Hemsleyadin
Bacillary dysentery
Hemsleya amabilis
Hesperidin
Capillary fragility
Citrus species
Hydrastine
Hemostatic, astringent
Hydrastis canadensis
Hyoscyamine
Anticholinergic
Hyoscyamus niger
Irinotecan
Anticancer, antitumor agent
Camptotheca acuminata
Kaibic acud
Ascaricide
Digenea simplex
Kawain
Tranquillizer
Piper methysticum
Kheltin
Bronchodilator
Ammi visaga
Lanatosides A, B, C
Cardiotonic
Digitalis lanata
Lapachol
Anticancer, antitumor
Tabebuia sp.
a-Lobeline
Smoking deterrant, respiratory stimulant
Lobelia inflata
Menthol
Rubefacient
Mentha species
Methyl salicylate
Rubefacient
Gaultheria procumbens
Monocrotaline
Antitumor agent (topical)
Crotalaria sessiliflora
Morphine
Analgesic
Papaver somniferum
Neoandrographolide
Dysentery
Andrographis paniculata
Nicotine
Insecticide
Nicotiana tabacum
Nordihydroguaiaretic acid
Antioxidant
Larrea divaricata
Noscapine
Antitussive
Papaver somniferum
Ouabain
Cardiotonic
Strophanthus gratus
Pachycarpine
Oxytocic
Sophora pschycarpa
Palmatine
Antipyretic, detoxicant
Coptis japonica
Papain
Proteolytic, mucolytic
Carica papaya
Papavarine
Smooth muscle relaxant
Papaver somniferum
Phyllodulcin
Sweetner
Hydrangea macrophylla
Physostigmine
Cholinesterase Inhibitor
Physostigma venenosum
Picrotoxin
Analeptic
Anamirta cocculus
Pilocarpine
Parasympathomimetic
Pilocarpus jaborandi
Pinitol
Expectorant
Several plants
Podophyllotoxin
Antitumor anticancer agent
Podophyllum peltatum
Protoveratrines A, B
Antihypertensives
Veratrum album
Pseudoephredrine*
Sympathomimetic
Ephedra sinica
Pseudoephedrine, nor-
Sympathomimetic
Ephedra sinica
Quinidine
Antiarrhythmic
Cinchona ledgeriana
Quinine
Antimalarial, antipyretic
Cinchona ledgeriana
Qulsqualic acid
Anthelmintic
Quisqualis indica
Rescinnamine
Antihypertensive, tranquillizer
Rauvolfia serpentina
Reserpine
Antihypertensive, tranquillizer
Rauvolfia serpentina
Rhomitoxin
Antihypertensive, tranquillizer
Rhododendron molle
Rorifone
Antitussive
Rorippa indica
Rotenone
Piscicide, Insecticide
Lonchocarpus nicou
Rotundine
Analagesic, sedative, traquillizer
Stephania sinica
Rutin
Capillary fragility
Citrus species
Salicin
Analgesic
Salix alba
Sanguinarine
Dental plaque inhibitor
Sanguinaria canadensis
Santonin
Ascaricide
Artemisia maritma
Scillarin A
Cardiotonic
Urginea maritima
Scopolamine
Sedative
Datura species
Sennosides A, B
Laxative
Cassia species
Silymarin
Antihepatotoxic
Silybum marianum
Sparteine
Oxytocic
Cytisus scoparius
Stevioside
Sweetner
Stevia rebaudiana
Strychnine
CNS stimulant
Strychnos nux-vomica
Taxol
Antitumor agent
Taxus brevifolia
Teniposide
Antitumor agent
Podophyllum peltatum
a-Tetrahydrocannabinol(THC)
Antiemetic, decrease occular tension
Cannabis sativa
Tetrahydropalmatine
Analgesic, sedative, traquillizer
Corydalis ambigua
Tetrandrine
Antihypertensive
Stephania tetrandra
Theobromine
Diuretic, vasodilator
Theobroma cacao
Theophylline
Diuretic, brochodilator
Theobroma cacao and others
Thymol
Antifungal (topical)
Thymus vulgaris
Topotecan
Antitumor, anticancer agent
Camptotheca acuminata
Trichosanthin
Abortifacient
Trichosanthes kirilowii
Tubocurarine
Skeletal muscle relaxant
Chondodendron tomentosum
Valapotriates
Sedative
Valeriana officinalis
Vasicine
Cerebral stimulant
Vinca minor
Vinblastine
Antitumor, Antileukemic agent
Catharanthus roseus
Vincristine
Antitumor, Antileukemic agent
Catharanthus roseus
Yohimbine
Aphrodisiac
Pausinystalia yohimbe
Yuanhuacine
Abortifacient
Daphne genkwa
Yuanhuadine
Abortifacient
Daphne genkwa

Nuclear MEDICINE

Nuclear MEDICINE
Nuclear medicine is a branch of medicine and medical imaging that uses the nuclear properties of matter in diagnosis and therapy. More specifically, nuclear medicine is a part of molecular imaging because it produces images that reflect biological processes that take place at the cellular and subcellular level.