Putting a spring in your step with strychnine

Everyone should be familiar with this favourite of crime fiction. Strychnine is not the most poisonous substance known to man (you need at least 50 mg to kill someone), but a you'd have to go a long way to find something that provokes a more violent death. So why the hell would you try to use it as a medicine?

Strychnine has two notable actions. Firstly, its taste is intensely bitter, and can be detected in quite dilute solutions. Secondly, it blocks receptors for the neurotransmitter glycine, which is present in the spinal cord, brain and retina. Glycine is an inhibitory neurotransmitter, meaning that when it is released and binds to receptors on other neurons, its effect is to reduce neuronal activity. It is important in the spinal cord, most notably because inhibitory neurons are required in the quite precise way the nervous system controls our muscles. When one muscle contracts, the neuronal circuitry in the spinal cord simultaneously ensures that any apposing muscles do not, using inhibitory neurotransmission to the neurons that control them. If you block glycine receptors, the delicate control system is lost and the result is violent, uncontrollable convulsions all over the body. Eventually, control of respiration ceases and death follows. Because glycine is also an inhibitory neurotransmitter in the eye, victims often notice visual disturbances as well.

Strychnine is isolated from nux vomica, the seeds of Strychnos nux-vomica. Nux vomica may ring a few bells, because it is a favourite of homeopaths. Of course, homeopaths dilute strychnine down until no active ingredient can possibly be left, and like all their potions, nux vomica is nothing but water. Conventional medicine, it turns out, has treated strychnine in a ironically similar way. It is the bitter taste of strychnine that is the key to this interesting story.

Strychnine was promoted as a "tonic" (a dangerously vague term) well into the twentieth century, having first appeared in routine medical use in the 18 century. It properties as a tonic were thought to be two-fold: stimulation of appetite and digestion and an increase in the excitability of muscle. You can taste the bitterness of strychnine at quite dilute, and harmless, concentrations. Bitterness was long held to stimulate the stomach, and indeed there is something to this theory. Reflex (Pavlovian, if you like) stimulation of gastric secretion by a bitter taste in the mouth probably does occur. Most 'digestive' drinks in many cultures have a bitter taste. But remember, this is all about bitterness, and not any effect on the central nervous system. The supposed effect on the excitability of muscles was presumed, based on the observations of the effects of poisoning; it was thought that at lower doses a useful, milder version of events would unfold. Although it sounds reasonable, the doses of strychnine that were taken for the 'tonic' effect would have no effect on the nervous system at all. To quote my battered copy of Goodman and Gilman's The pharmacological basis of therapeutics (1975):

"To the drug have been ascribed properties that it does not possess, or that is exhibits only when administered in toxic doses"

People took this bitter placebo for a couple of hundred years, all the same.