Drugs acting in the central nervous system (CNS) were among the first to be discovered by primitive humans and are still the most widely used group of pharmacologic agents. In addition to their use in therapy, many drugs acting on the CNS are used without prescription to increase the sense of well-being.
The mechanisms by which various drugs act in the CNS have not always been clearly understood. In recent decades, however, dramatic advances have been made in the methodology of CNS pharmacology. It is now possible to study the action of a drug on individual cells and even single ion channels within synapses. The information obtained from such studies is the basis for several major developments in studies of the CNS.
First, it is clear that nearly all drugs with CNS effects act on specific receptors that modulate synaptic transmission. A very few agents such as general anesthetics and alcohol may have nonspecific actions on membranes (although these exceptions are not fully accepted), but even these non–receptor-mediated actions result in demonstrable alterations in synaptic transmission.
Second, drugs are among the most important tools for studying all aspects of CNS physiology, from the mechanism of convulsions to the laying down of long-term memory. As described below, agonists that mimic natural transmitters (and in many cases are more selective than the endogenous substances) and antagonists are extremely useful in such studies. The section, Natural Toxins: Tools for Characterizing Ion Channels, describes a few of these substances.
Natural Toxins: Tools for Characterizing Ion Channels
Evolution is tireless in the development of natural toxins. A vast number of variations are possible with even a small number of amino acids in peptides, and peptides make up only one of a broad array of toxic compounds. For example, the predatory marine snail genus Conus is estimated to include at least 500 different species. Each species kills or paralyzes its prey with a venom that contains 50–200 different peptides or proteins. Furthermore, there is little duplication of peptides among Conus species. Other animals with useful toxins include snakes, frogs, spiders, bees, wasps, and scorpions. Plant species with toxic (or therapeutic) substances are too numerous to mention here; they are referred to in many chapters of this book.
Since many toxins act on ion channels, they provide a wealth of chemical tools for studying the function of these channels. In fact, much of our current understanding of the properties of ion channels comes from studies utilizing only a small percentage of the highly potent and selective toxins that are now available. The toxins typically target voltage-sensitive ion channels, but a number of very useful toxins block ionotropic neurotransmitter receptors. Table 21–1 lists some of the toxins most commonly used in research, their mode of action, and their source.
Table 21–1 Some Toxins Used to Characterize Ion Channels.