Corticosteroids have been used as drug treatment for some time. Lewis Sarett of Merck & Co. was the first to synthesize cortisone, using a complicated 36-step process that started with deoxycholic acid, which was extracted from ox bile .  The low efficiency of converting deoxycholic acid into cortisone led to a cost of US $200 per gram. Russell Marker , at Syntex , discovered a much cheaper and more convenient starting material, diosgenin from wild Mexican yams . His conversion of diosgenin into progesterone by a four-step process now known as Marker degradation was an important step in mass production of all steroidal hormones, including cortisone and chemicals used in hormonal contraception .  In 1952, . Peterson and . Murray of Upjohn developed a process that used Rhizopus mold to oxidize progesterone into a compound that was readily converted to cortisone.  The ability to cheaply synthesize large quantities of cortisone from the diosgenin in yams resulted in a rapid drop in price to US $6 per gram, falling to $ per gram by 1980. Percy Julian's research also aided progress in the field.  The exact nature of cortisone's anti-inflammatory action remained a mystery for years after, however, until the leukocyte adhesion cascade and the role of phospholipase A2 in the production of prostaglandins and leukotrienes was fully understood in the early 1980s.
In a double-blind randomized controlled trial that evaluated the emergency department treatment of migraine in 66 patients, the combination of IV prochlorperazine (10 mg) and IV diphenhydramine ( mg) was significantly more effective than subcutaneous sumatriptan (6 mg) for the reduction of pain intensity at 80 minutes or time of discharge [ 78 ]. Diphenhydramine was used with prochlorperazine to prevent akathisia and dystonic reactions. However, the possibility of migraine benefit from diphenhydramine cannot be completely discounted. A high drop-out rate upon attempted telephone contact at 72 hours precluded meaningful assessment of headache recurrence, although none of the enrolled patients returned to the emergency department with complaint of headache.