Tuesday, September 15, 2015

Weird drug logic

In the past, pharmacology was a rather, shall we say, murky area of study. Figuring out how to treat an ailment using a drug sometimes involved a lot of educated guessing, and oftentimes the information backing up a guess wasn't particularly solid. Let's look at a couple of examples of the historically weird logic behind drug treatments.

In 1857, the famous medical journal The Lancet published an article by Sir Charles Locock, a British obstetrician who had recently retired after a storied career during which he delivered all of Queen Victoria's children. In this article, Locock recommended the use of potassium bromide (often flavoured with licorice) for the treatment of epilepsy. While this proved to be a success (it saw use for the next 100 or so years before being replaced by better drugs), the reasoning behind it was super strange. At the time, masturbation (and, more generally, just being really turned on all the time) was thought to be a major cause of epilepsy (totally wrong), and potassium bromide had been reported to reduce one's sex drive (it does make people sleepy, admittedly). Locock put two and two together, and an antiepileptic drug was accidentally born.

An alkaloid produced by a genus of shrubs (Pilocarpus, common name jaborandi) found in South America, pilocarpine was once included in hair tonic nostrums due to the mistaken belief it could combat hair loss. This idea came about in part because the drug had previously been determined to act on sebaceous glands, tiny skin-based pockets connected to hair follices. Although these glands secrete a mixture of hair-moisturizing lipids (sebum), they don't have anything to do with the development of male pattern baldness. A second line of reasoning was based on pilocarpine being capable of stimulating the parasympathetic nervous system, which operates alongside the sympathetic nervous system to regulate unconscious body functions like producing sweat or saliva. These two systems complement one other. For example, while the parasympathetic system acts to speed up the movement of digesting food through the intestines, this process is inhibited by the sympathetic system. For a time, it was thought that the element thallium, compounds of which cause hair loss, acted through the sympathetic system (nope). Based on this thinking, stimulation of the opposing parasympathetic system using pilocarpine should treat baldness. In actual fact, thallium compounds are just very toxic, with hair loss being a symptom of widespread cell damage.

Pilocarpus species are named for their cap-shaped fruit (Source)

Deadly nightshade (Atropa belladonna) is a poisonous plant fearlessly consumed by rabbits. Its toxicity is due to anticholinergic alkaloids including scopolamine and hyoscyamine, which in lower doses can be used to treat motion sickness, nausea and vomiting after surgery, and various gastrointestinal issues. They've also been used to control some of the symptoms of Parkinson's disease. For the latter use, nightshade plants from Bulgaria were briefly and incorrectly thought to be more effective than plants grown elsewhere. See, in 1926, a biologist from Shipka came up with an elaborate treatment regime for Parkinson's disease based around a decoction of nightshade root made with wine. This approach was apparently very successful, leading many to believe there were special qualities possessed by nightshade plants grown in Bulgaria. However, several studies did not find any significant difference between plants from Bulgaria and from several other European countries. Instead, the particular success of Bulgarian nightshade was attributed to the extra features of the treatment regime it was used with (e.g. physical therapy and extra nursing care).


References

Goodman L, Gilman A. 1941. The pharmacological basis of therapeutics. Macmillan Company.

Meidan VM, Touitou E. 2001. Treatments for androgenetic alopecia and alopecia areata: Current options and future prospects. Drugs 61(1):53-69.

Price JC, Merritt HH. 1941. The treatment of Parkinsonism: Results obtained with wine of Bulgarian belladonna and the alkaloids of the USP belladonna. Journal of the American Medical Association 117(5):335-337. [First page]

Rattner H. 1941. Ordinary baldness: President's address. Archives of Dermatology and Syphilology 44(2):201-213. [First page]

Zouboulis CC, Baron JM, Böhm M, Kippenberger S, Kurzen H, Reichrath J, Thielitz A. 2008. Frontiers in sebaceous gland biology and pathology. Experimental Dermatology 17(6):542-551. [Full text]

http://www.rsc.org/chemistryworld/2013/11/potassium-bromide-sedative-trenches-tea

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