Alkaloid

Alkaloids are organic chemical compounds found primarily in certain plant species. Although many types of alkaloids exist, all alkaloid compounds have certain characteristics in common. Specifically, all alkaloids have complex chemical structures that include at least one nitrogen molecule and all have some sort of physiological effect on the human body. All alkaloids also react with acids to form salts. While many alkaloids are used for medicinal purposes, others are toxic enough to be considered potentially deadly. The seven major categories of alkaloids are tropanes, isoquinolines, pyridines, pyrrolizidines, quinolones, indoles, and purines. Within each of these categories are many individual alkaloids with different properties and chemical structures. Some of the most common and best-known alkaloids include caffeine, cocaine, and the deadly nightshade-derived atropine. In total, researchers have identified more than ten thousand known alkaloids with a more varied array of chemical structures than are found in any other natural product.

Brief History

Humans have been aware of the existence of alkaloids since the dawn of civilization. In fact, people have used alkaloids for medicinal purposes and in the production of various potions, teas, and poisons for at least four thousand years. One of the earliest and most common uses of alkaloids was as the deadly ingredient in poison-tipped arrows made for hunting and warfare. The term alkaloid was first proposed by pharmacist W. Meissner in 1819 to describe simple nitrogen-containing compounds found in plants. It did not, however, enjoy wide use until after it appeared in a review article in Albert Ladenburg's chemical dictionary in 1880.

The use of alkaloids for medicinal purposes arose gradually over time as people learned more about their potential healing properties. Most of the alkaloids used in medicine were isolated beginning only in the early nineteenth century. The first crude drug from which an alkaloid was definitively isolated was opium, which was long used as a narcotic and analgesic. In 1803, French pharmacist and chemist Jean-François Derosne successfully isolated this alkaloid and German pharmacist Friedrich Sertürner shortly thereafter identified it as morphine. This breakthrough eventually led to the beginning of the most prolific period of alkaloid isolation in history.

Starting in 1817, French pharmacists Joseph Caventou and Pierre Pelletier embarked on a remarkably successful effort to isolate alkaloids at the Faculty of Pharmacy in Paris. By the time they concluded their work in 1820, the pair had isolated more alkaloids from crude substances than any other single laboratory has isolated since. Some of the many alkaloids that Caventou and Pelletier successfully isolated included strychnine, caffeine, emetine, piperine, cinchonine, brucine, quinine, and colchicine. Ultimately, the work completed by Caventou and Pelletier set the stage for all of the advancements in alkaloid chemistry that have been made since that time.

As research continued, an ever-growing number of alkaloids were isolated. The number of alkaloids that had been isolated and structurally identified totaled approximately two hundred in 1939. By the late 1980s, that number soared to about ten thousand and continued to grow as scientists isolated more alkaloids in laboratories around the world.

Overview

Estimates suggest that alkaloids are found in anywhere from 10 to 25 percent of all plants, particularly among the members of the Apocynaceae, Asteraceae, Berberidaceae, Boraginaceae, Fabaceae, Papaveraceae, Ranunculaceae, Rubiaceae, Rutaceae and Solanaceae plant families. It is not clear exactly why alkaloids are this common, though researchers have developed several extant theories. One such theory holds that plants rely on alkaloids for the removal of excess nitrogen. Another hypothesizes that plants actually use alkaloids to store nitrogen for future use. A third theory postulates that plants use alkaloids—especially those that are poisonous—as a natural way of protecting themselves from being consumed by insects and other animals.

Alkaloids also have a noted effect on humans and other animals. Most importantly, alkaloids serve to either block or intensify the actions of neurotransmitters. Neurotransmitters are special chemicals released by nerve cells in response to a type of electrical stimuli known as a neural signal. When neurotransmitters are released, they diffuse into nearby cells and produce some sort of response, such as a contraction in a muscle cell. In effect, alkaloids alter the responses generated by the release of neurotransmitters.

Each of the seven alkaloid categories includes a range of related individual alkaloids with different properties, effects, and uses. Tropane alkaloids are synthesized from certain amino acids and are largely found in plants of the Solanaceae family. All tropane alkaloids are also anticholinergic, which means that they block a specific neurotransmitter called acetylcholine. Medicinally, tropane alkaloids are typically used to counteract muscle spasms and reduce secretions in the digestive tract. Some notable tropane alkaloids include atropine and the addictive narcotic cocaine.

Isoquinoline alkaloids are synthesized from the amino acid tyrosine. Many act as digestive stimulants, analgesics, expectorants, or antitussives. Some common isoquinoline alkaloids include codeine, morphine, and berberine.

Pyridine alkaloids are synthesized from the amino acid lysine. Some of these alkaloids are used as expectorants or to increase gut permeability. Among the most notable pyridine alkaloids are nicotine, lobeline, and piperine.

Pyrrole alkaloids are synthesized from the amino acid ornithine. Although these alkaloids are not widely used for medicinal purposes, several varieties exist. Some of these include hymenidin and sceptrin.

Pyrrolizidine alkaloids are also synthesized from the amino acid ornithine. These alkaloids are frequently hepatotoxic, which means that they can damage or even destroy liver cells. Sufficient exposure to pyrrolizidine alkaloids can result in liver failure and death. Examples of this type of alkaloid include retrorsine and symphytine.

Quinoline alkaloids are synthesized from the amino acid tryptophan or the alkaloid tryptamine. Some are used to treat malaria or as digestive stimulants or tonics. Examples include quinine, quinidine, and cusparine.

Indole alkaloids are also synthesized from tryptophan or tryptamine. This group contains some of the most active alkaloid agents, some of which are used to treat migraines and even cancer. Examples include vincristine, reserpine, and strychnine.

Purine alkaloids are synthesized from the purine nucleic acid xanthine. Many of these alkaloids function as central nervous system stimulants and diuretics. Examples include caffeine, theobromine, and theophylline.

Bibliography

"Alkaloids." The Naturopathic Herbalist, thenaturopathicherbalist.com/plant-constituents/alkaloids/. Accessed 21 June 2017.

Aniszewski, Tadeusz. Alkaloids: Chemistry, Biology, Ecology, and Applications. Elsevier, 2015.

Buckingham, John, et al. Dictionary of Alkaloids, Second Edition with CD-ROM. CRC Press, 2010.

Funayama, Shinji and Geoffrey A. Cordell. Alkaloids: A Treasury of Poisons and Medicines. Elsevier, 2014.

Hesse, Manfred. Alkaloids. Wiley-VCH, 2002.

Roberts, Margaret F. Alkaloids: Biochemistry, Ecology, and Medicinal Applications. Springer Science & Business Media, 2013.

Saxena, P.B. Chemistry of Alkaloids. Discovery Publishing House, 2007.

"What Is an Alkaloid?" wiseGEEK, www.wisegeek.com/what-is-an-alkaloid.htm. Accessed 21 June 2017.