Alkaloid

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Alkaloid

Alkaloids are chemical compounds found in plants that can react with acids to form salts. All alkaloids contain the element nitrogen , usually in complex, multi-ring structures.

Role in the plant

Between 10% and 15% of all plants contain some type of alkaloid. It is unclear why alkaloids are so common, and it is a matter of controversy among scientists. Some believe that plants rid themselves of excess nitrogen through the production of alkaloids just as humans and other mammals convert excess nitrogen into urea to be passed in the urine. Some modify this theory by suggesting that plants use alkaloids to temporarily store nitrogen for later use, instead of discarding altogether this difficult-to-obtain element.

Perhaps the most likely theory is that the presence of alkaloids discourages insects and animals from eating plants. The poisonous nature of most alkaloids supports this theory, although various alkaloids that are employed in small quantities for specific purposes can be useful to man.

Role in animals

Many alkaloids act by blocking or intensifying the actions of neurotransmitters, chemicals released by nerve cells in response to an electrical impulse called a neural signal. Neurotransmitters diffuse into neighboring cells where they produce an appropriate response, such as an electrical impulse, in another nerve cell or contraction in a muscle cell.

Each nerve cell produces only one type of neurotransmitter ; acetylcholine and norepinephrine are the most common. Cells may respond to more than one type of neurotransmitter, however, and the response to each type may be different.

Medical use

A number of alkaloids are used as drugs. Among the oldest and best known of these is quinine , derived from the bark of the tropical cinchona tree . Indians of South America have long used cinchona bark to reduce fever, much as willow bark was used in Europe as a source of aspirin. In the 1600s Europeans discovered that the bark could actually cure malaria—one of the most debilitating and fatal diseases of tropical and subtropical regions.

Quinine was purified as early as 1823, and soon it replaced crude cinchona bark as the standard treatment for malaria . Not until the 1930s was quinine replaced by synthetic analogues that offered fewer side effects and a more reliable supply. Quinine is still used as the principal flavoring agent in tonic water—a beverage named for its ability to prevent malarial symptoms.

Cinchona bark also produces quinidine. It is used primarily to control abnormalities of heart rhythm such as fibrillation, a series of rapidly quivering beats that do not pump any blood , and heart block, a condition in which electrical currents fail to coordinate the contractions of the upper and lower chambers of the heart.

Vincaleukoblastine and vincristine, two alkaloids derived from the periwinkle plant (Catharanthus roseus), are used effectively for the treatment of white-blood-cell cancers. Vincaleukoblastine is especially useful against lymphoma (cancer of the lymph glands ), while vincristine is used against the most common form of childhood leukemia .

Atropine is an alkaloid produced by several plants, including deadly nightshade (Atropa belladonna), Jimson weed (Datura stramonium), and henbane (Hyoscyamus niger). It has a variety of medical uses, as it is able to relax smooth muscle by blocking action of the neurotransmitter acetylcholine. Atropine is most commonly used to dilate the pupil during eye examinations. Atropine also relieves nasal congestion and serves as an antidote to nerve gas and insecticide poisoning.

Pilocarpine, derived from several Brazilian shrubs of the genus Pilocarpus, is another alkaloid used in ophthalmology, the medical specialty that treats the eye. This drug stimulates the drainage of excess fluid from the eyeball, relieving the high pressure in the eye caused by glaucoma. If untreated, glaucoma can lead to blindness.

Introduction of reserpine in the 1950s revolutionized high blood pressure treatment and brought new hope to those suffering from this previously untreatable and life-threatening condition. Derived from tropical trees and shrubs of the genus Aauwolfia, reserpine works by depleting the body's stores of the neurotransmitter norepinephrine. Among its other functions, norepinephrine contracts the arteries and thereby contributes to high blood pressure.

Unfortunately, reserpine also causes drowsiness and sometimes severe depression . Medications without these side effects have been developed in recent decades, and reserpine is rarely used.

Alkaloids for pain and pleasure

Many medically useful alkaloids act by way of the peripheral nervous system ; others work directly on the brain . Prominent among the latter are the pain relievers morphine and codeine , derived from the opium poppy (Papaver somniferum). Morphine is the stronger of the two, but codeine is often prescribed for moderate pain. Codeine is also an effective cough suppressant; for years it was a standard component of cough syrups. Now, however, it has been replaced for the most part by drugs that do not have the psychological side effects of codeine.

Both morphine and codeine are addictive drugs that produce a state of relaxed, dreamy euphoria—an exaggerated state of "feeling good," referred to by drug addicts as a "high." The equivalent street drug is heroin, derived from morphine by a simple chemical modification. Heroin addicts typically believe that their drug is stronger and produces a more pronounced "high" than morphine; however, since heroin is rapidly converted to morphine once it enters the body, most medical scientists consider the two drugs completely equivalent.

The effects of cocaine are almost the opposite of those of morphine; cocaine's legal classification as a narcotic—a drug that produces stupor—is misleading from a medical standpoint. This product of the coca plant, native to the Andes Mountains in South America, produces a state of euphoric hyperarousal. The user feels excited, elated, and intensely aware of his or her surroundings, with an impression of enhanced physical strength and mental ability. These feelings are accompanied by the physical signs of arousal: elevated heart rate and blood pressure. The increased heart rate caused by a high dose may lead to fibrillation and death.

A cocaine "high," unlike the "highs" from most abused drugs, lasts less than half an hour—often much less. Once an individual becomes addicted, he or she needs large amounts of the expensive drug. Users' enhanced aggressiveness and physical self-confidence further increase cocaine's social dangers. Cocaine usage over time can result in paranoid schizophrenia , a type of insanity characterized by unfounded suspicion and fantasies of persecution; when this psychological condition is combined with continued cocaine use, the addict may perform violent acts against the supposed plotters.

Cocaine is also a local anesthetic, and was used medically for that purpose in the early part of the century. Procaine and xylocaine, synthetic local anesthetics introduced during the mid-1900s, have replaced cocaine as a medical drug.

Another pleasurable yet addictive drug is nicotine , usually obtained by either smoking or chewing leaves of the tobacco plant, Nicotiana tabacum. Ground-up leaves, known as snuff, may be placed in the nose or cheek, allowing the nicotine to diffuse through the linings of the cavities into the bloodstream.

With the possible exception of alcohol , nicotine is the world's most widely used addictive drug. Its attractiveness undoubtedly results from the drug's paradoxical combination of calming and stimulating properties—it can produce either relaxation or arousal, depending on the user's state. Its physical effects, however, are primarily stimulatory. By increasing the heart rate and blood pressure while constricting the arteries—including those in the heart—nicotine significantly increases the risk of a heart attack.

Some alkaloid stimulants are not addictive, however. These include caffeine and the related compounds theophylline and theobromine. Caffeine is found in coffee, made from beans of Coffea arabica; in tea, from leaves of Camellia sinensis; in cocoa and chocolate, from seeds of Theobroma cacao; and in cola drinks, which contain flavorings derived from nuts of Cola plants. In northern Argentina and southern Brazil, leaves of Ilex paraguariensis (a type of holly) are used to make maté, a drink more popular there than either coffee or tea.

In addition to caffeine, tea also contains small amounts of theophylline, while theobromine is the major stimulant in cocoa. Large amounts of coffee, tea, cocoa, or cola drinks (more than 6-12 cups of coffee a day, for example), can produce nervousness, shakiness (muscle tremors), and insomnia , and may increase the risk of heart attack. Adverse effects from smaller amounts of these beverages have been claimed but never clearly demonstrated.

Black pepper falls into an entirely different category of the pain/pleasure grouping. This spice derives its burning flavor primarily from the alkaloids piperine, piperidine, and chavicine.

Addiction

Addiction was originally defined by the appearance of physical symptoms—such as sweating, sniffling, and trembling—when a drug was withdrawn from an addicted person or animal . It was also thought that addiction was accompanied by adaptation , in which more and more of the drug is required to produce the same effect.

So long as the focus was on opium-derived drugs such as morphine and heroin, this definition was appropriate. Beginning in the 1960s, however, scientists realized that it did not define the properties that render cocaine and other drugs so dangerous. Cocaine does not produce adaptation, and its withdrawal does not result in physical symptoms that can be seen in laboratory animals. Cocaine withdrawal does, however, produce an intense depression that disappears when the drug is again available. Similarly, nicotine withdrawal produces psychological symptoms such as restlessness, anxiety , irritability, difficulty in concentrating, and a craving for the drug. Today these psychological withdrawal symptoms are recognized as valid indicators of addiction.

Poisonous alkaloids

Nearly all of the alkaloids mentioned so far are poisonous in large amounts. Some alkaloids, however, are almost solely known as poisons. One of these is strychnine, derived from the small Hawaiian tree Strychnos nux-vomica. Symptoms of strychnine poisoning begin with feelings of restlessness and anxiety, proceeding to muscle twitching and exaggerated reflexes. In severe poisoning, a loud sound can cause severe muscle spasms throughout the entire body. These spasms may make breathing impossible and result in death.

In the early part of the twentieth century, strychnine was widely used as a rat poison. In recent decades, however, slower-acting poisons have been used for rodent control; since rats can remember which foods have made them sick, one that receives a non-fatal dose of a fast-acting poison such as strychnine will never again take that type of poisonous bait.

A number of other plants also derive their lethal properties from alkaloids of one type or another. Among these are poison hemlock (Conium maculatum) and plants of the genus Aconitum, commonly called monkshood—known by devotees of werewolf stories as wolfsbane. Other examples include shrubs of the genus Calycanthus, known as Carolina allspice, spicebush, and sweet betty, among other names; vines of the genus Solandra, such as the chalice vine, cup-of-gold, silver cup, and trumpet plant; trees or shrubs of the genus Taxus, such as yews; plants of the lily-like genus Veratrum, including false hellebore; and the golden chain or bean tree (Laburnum anagyroides).

Although vines and non-woody plants of the genus Solanum pose a real danger only to children, they represent an extremely varied group. Poisonous members of this genus range from the common potato to the nightshade (not the same as the deadly nightshade that produces atropine). The group also includes the Jerusalem cherry, the false Jerusalem cherry, the love apple, the Carolina horse nettle, the bittersweet, the nipplefruit, the star-potato vine, and the apple of Sodom.

Poisoning by ordinary potatoes usually results from eating uncooked sprouts or sun-greened skin. These parts should be cut away and discarded. For other plants in the group, it is the immature fruit that is most likely to be poisonous. In contrast to the nervous-system effects of most alkaloids, the alkaloids found in the genus Solanum produce mainly fever and diarrhea.