and similar guanidine analogues were investigated until the ultimate discovery of cimetidine. the compound was synthesized in 1972 and evaluated for toxicology by 1973. it passed all trials. cimetidine was first marketed in the united kingdom in 1976, and in the u.s. in august 1977; therefore, it took 12 years from initiation of the h2 receptor antagonist program to commercialization. by 1979, tagamet was being sold in more than 100 countries and became the top-selling prescription product in the u.s., canada, and several other countries. in november 1997, the american chemical society and the royal society of chemistry in the u.k. jointly recognized the work as a milestone in drug discovery by designating it an international historic chemical landmark during a ceremony at smithkline beecham's new frontiers science park research facilities in harlow, england. the commercial name "tagamet" was decided upon by fusing the two words "antagonist" and "cimetidine". subsequent to the introduction onto the u.s. drug market, two other h2 receptor antagonists were approved, ranitidine (zantac, glaxo labs) and famotidine (pepcid, yamanouchi, ltd.) cimetidine became the first drug ever to reach more than $1 billion a year in sales, thus making it the first blockbuster drug. in a deal expected to take effect in 2012, glaxosmithkline sold tagamet and 16 other brands to prestige brands. tagamet has now been largely replaced by the proton pump inhibitors for treating peptic ulcers, but is now available as an over-the-counter medicine for heartburn in many countries.