of people with epilepsy, thereby realigning the bone plates of the skull, taking pressure
off the brain, and alleviating the curse of epilepsy.
By the Middle Ages, alchemy and astronomy formed the scientific foundations of
epilepsy therapy. The use of “magical prescriptions” flourished. These remedies ranged
from grotesque therapies, such as the ingestion of dog bile or human urine, to the use of
somewhat more innocuous precious stone amulets. During the Renaissance, these magi-
cal treatments were rejected by the medical profession in favor of “rational and scientific”
Galenic therapies. These treatments relied extensively upon forced vomiting and bowel
purging with concomitant oral administration of peony extracts. Also, during this time, the
notion of epilepsy being secondary to hypersexuality emerged, and castration, circumci-
sion, or clitoridectomy were widely advocated. Occasionally, various pharmacologically
active organic molecules (e.g., strychnine, curare, atropine, valerian, picrotoxin, and qui-
nine) were also used, but all ultimately failed—sometimes killing the unfortunate patient.
Inorganic salts were also considered as putative therapies during the late Renaissance.
Copper-based therapy flourished during the eighteenth and nineteenth centuries. Aretaios
had introduced the use of antiepileptic copper salts in the first century AD, and had
described significant therapeutic successes. These reported successes with copper therapy
were embraced during the 1700s, leading to other therapeutic attempts with lead, bismuth,
tin, silver, iron, and mercury, thus giving rise to metallotherapy. The subsequent wide-
spread failure of metallotherapy, due to lack of efficacy and excessive toxicity, led to its
abandonment during the late pre-modern era.
Thus, in the millennia extending from antiquity to the mid-nineteenth century,
epilepsy remained a medical condition surrounded by mystique—permitting charla-
tanism, superstition, and quackery to prosper. In general, the therapies of this time were
without merit, as demonstrated by the detailed but disturbing description of King
Charles II’s death, which provides a comprehensive summary of the complexity and
futility of seizure therapy during the pre-modern era.
In 1685, the king fell backward and had a violent convulsion. Treatment was
begun immediately by a dozen physicians. He was bled to the extent of 1 pint
from his right arm. Next, his shoulder was incised and cupped, depriving him of
another 8 oz. of blood. After an emetic and 2 purgatives, he was given an enema
containing antimony, bitters, rock salt, mallow leaves, violets, beet root,
chamomile flowers, fennel seed, linseed, cinnamon, cardamom seed, saffron and
aloes. The enema was repeated in 2 hours and another purgative was given. The
king’s head was shaved and a burn blister was raised on his scalp. A sneezing
powder of hellebore root and one of cowslip flowers were administered to
strengthen the king’s brain. Soothing drinks of barley water, licorice and sweet
almond were given, as well as extracts of mint, thistle leaves, rue, and angelica.
For external treatment, a plaster of Burgundy pitch and pigeon dung was liberally
applied to the king’s feet. After continued bleeding and purging, to which were
added melon seed, manna, slippery elm, black cherry water, and dissolved pearls,
the king’s condition did not improve and, as an emergency measure, 40 drops
of human skull extract were given to allay convulsions. Finally, bezoar stone
was forced down the king’s throat and into his stomach. As the king’s condition
grew increasingly worse, the grand finale of Raleigh’s antidote, pearl julep, and
ammonia water were pushed into the dying king’s mouth. (Swinyard, 1980)DESIGNING DRUG MOLECULES TO FIT RECEPTORS 109