Chapter 6 Pharmacological activities of natural products

As indicated in Chapter 2, a valid scheme for the study of medicinal plants and their products, and one which emphasizes pharmaceutical use, can be based on pharmacological action. The scheme can be extended to include numerous plants which, although eliciting a pharmacological response, are not, for varied reasons, used as drugs. In the latter category would be placed hundreds of alkaloid- and glycoside-containing plants.

Some major pharmacological groupings involve drugs which act on the nervous systems, heart and blood vessels, lungs, gastrointestinal tract, kidneys, liver, reproductive organs, skin and mucous membranes. Other categories include hormones, vitamins and chemotherapeutic drugs used for the treatment of infections and malignant diseases. Some plants (e.g. Papaver, ipecacuanha and liquorice) contain a range of compounds with differing pharmacological properties. Oliver-Bever’s classical review (J. Ethnopharmacol., 1983, 7, 1) on West African plants which act on the nervous system well illustrates the problems of constructing a purely pharmacological classification for herbal materials. A system based on clinical usage may be more straightforward for the throughly studied allopathic drugs used in Western medicine but difficulties can arise for plants used in traditional medicine because of the often numerous conditions for which any one drug may be employed. However, this is a very active area of research and the situation for a particular drug becomes clearer as the chemical nature of the active constituents together with their pharmacological properties are elucidated.

DRUGS ACTING ON THE NERVOUS SYSTEM

The nervous system coordinates and regulates the various voluntary and involuntary activities of the body and is conveniently considered under two headings—the central nervous system (CNS) and the autonomic nervous system. The two are interlinked and some drugs which affect the CNS may also produce reactions associated with the autonomic system. In the case of others which act via the autonomic system it is sometimes more convenient to classify them under other headings appropriate to the organs involved; thus, those producing vasoconstriction or vasodilation may appear under the consideration of the circulatory and respiratory systems.

THE CENTRAL NERVOUS SYSTEM

The central nervous system comprises the brain (cerebrum, cerebellum, medulla oblongata) and the spinal cord. It coordinates the voluntary activities of the body and exhibits numerous interactions within the system together with linkages to the autonomic system. Drugs involved with the CNS can be broadly classified according to whether they have a general stimulatory or depressant action with further subdivision regarding specific actions such as anticonvulsant and psychopharmacological activities. Some of the most useful natural drugs of the group are the narcotic (opioid) analgesics; a number of herbal drugs are popular sedatives and others such as the hallucinogenic drugs have important sociological implications. See Table 6.1 for a summary of drugs acting on the central nervous system.

Table 6.1 Drugs acting on the central nervous system.

Drugs affecting mental activity
Lysergic acid diethylamide	Hallucinogenic. Prepared by partial synthesis from ergot alkaloids or by artificial culture
Mescaline	Hallucinogenic. Obtained from peyote cactus
Cannabis	Hallucinogenic. Active constituents contained in the resin of Cannabis sativa
Purine bases (e.g. caffeine, theophylline, theobromine)	Stimulate mental activity; constituents of beverages—coffee, tea, cocoa, kola, maté
Cocaine	One of the earliest drugs used as a mental stimulant. Produces addiction. Contained in the leaves of Erythroxylum coca
Ginkgo biloba	Improves short term memory
Ginseng	Improves mental concentration particularly in the elderly
Galanthamine	Promising Amaryllidaceous alkaloid for treatment of Alzheimer’s disease
Hops	Sedative, often combined with other herbs
Hypericum	Popular herbal remedy for relief of mild–moderate depression
Passiflora	Treatment of insomnia often in combination
Sage	Revived interest in its use for counteracting memory loss
St John’s wort	Antidepressant, may adversely react with some mainstream drugs
Reserpine	Depresses mental activity. Used in psychiatric treatment. Obtained from Rauwolfia spp.
Yohimbine	Similar action to reserpine but its antiadrenaline reactions and effect on heart muscle render it of no clinical use. Found in various species of the Apocynaceae
Valerian	Sedative and hypnotic; aids sleeplessness and improves sleep quality
Analeptic drugs (stimulants of the CNS in addition to the mental stimulants indicated above)
Picrotoxin	Analeptic previously used in the treatment of barbiturate poisoning. Obtained from berries of Anamirta cocculus
Lobeline	Obtained from Lobelia inflata
Strychnine	Weak analeptic; toxic doses produce spinal convulsions. Obtained from the seeds of Strychnos spp.
Camphor	Weak analeptic. Obtained from Cinnamomum camphora and by synthesis
Central depressants of motor function
Tropane alkaloids (e.g. hyoscine, atropine, etc.)	Formerly the only drugs effective in the alleviation of the symptoms of Parkinson’s disease. Used in treatment of travel sickness and delirium tremens
Gelsemium root	Rarely employed clinically owing to high toxicity. Galenical preparations occasionally used as antispasmodics
Analgesic drugs
Morphine	Effective for relief of severe pain. Depressant action on the cough and respiratory centres. The principal alkaloid of opium
Codeine	Although less active than morphine it is a much safer drug for the relief of mild pain and for use as a cough suppressant

THE AUTONOMIC NERVOUS SYSTEM

The autonomic nervous system supplies the smooth muscle tissues and glands of the body. Its function is complex, involving ganglia situated outside the spinal cord; it is composed of two divisions, the sympathetic (thoracolumbar or adrenergic) division, which arises from the thoracic and lumbar regions; and the parasympathetic (craniosacral or cholinergic) division, originating in the brain and in the sacral region. In general, an increase in activity of the sympathetic system gears the body for immediate action (fight and flight), whereas stimulation of the parasympathetic or vagal system produces effects more associated with those occurring during sleep and with energy conservation. Two important neurotransmitter substances of the autonomic nervous system are acetylcholine and noradrenaline and its derivatives; hence, other substances which either mimic or antagonize the action of either of these will produce a marked physiological response. Drugs acting on the autonomic nervous system are summarized in Table 6.2.

Table 6.2 Drugs acting on the autonomic nervous system.

Acetylcholine-like drugs
Pilocarpine	From leaves of Pilocarpus microphyllus
Arecoline	From seeds of Areca catechu
Muscarine	From Amanita spp. and other fungi
Physostigmine	A cholinesterase inhibitor from seeds of Physostigma venenosum
Antagonists of acetylcholine
Tropane ester alkaloids (e.g. hyoscine, atropine)	From a number of Solanaceae (e.g. Duboisia, Atropa, Datura etc.) They have widespread uses involving their gastrointestinal, bronchial, genito-urinary and ophthalmic effects in addition to the CNS activity (q.v.)
Neuromuscular blocking agents (e.g. tubocurarine)	From leaves and stems of Chondodrendon tomentosum
Ganglion blocking agents (e.g. tubocurarine in large doses) (not clinically important)
Adrenaline-like drugs
Ephedrine	From stems of Ephedra spp.; mainly synthetic
Antagonists of adrenaline
Ergot alkaloids (e.g. ergotamine)	From sclerotia of Claviceps spp.
Noradrenaline depletion
Reserpine	Has antihypertensive effect resulting from dilation of heart and circulatory vessels
Ophthalmic preparations
The eye, being under the control of the autonomic nervous system, is affected by some of the drugs mentioned above; these include atropine, hyoscine, physostigmine and pilocarpine