Certain chemical properties, which may determine the stimulatory actions of the new histamine H2 receptor antagonist, FRG-8813 (2-(furfurylsulfinyl)-N-(4-[4-(piperidinomethyl)-2-pyridyl]o xy-(Z)- 2-butenyl)acetamide), on mucin biosynthesis, were identified by considering the derivation of this drug using an organ culture system of the rat stomach. [3H]Glucosamine and [35S]sulfate incorporation was stimulated in the corpus region by FRG-8813 and its structural analog, compound A (N-[4-[[4- (piperidinylmethyl)pyridyl]-2-oxy]-(Z)-2-butenyl]phthalimide). The chronotropic response to histamine in the guinea pig right atria was suppressed by FRG-8813 in a concentration-dependent fashion. In contrast, compound A did not suppress the histamine-induced response. Ranitidine at 10(-4) M did not suppress the FRG-8813-induced increase in [3H]glucosamine incorporation into mucin. These results suggest that the pyridine derivative and amide structure are chemically important in FRG-8813 as a stimulant on mucus metabolism. Also, this effect is not directly due to histamine H2 receptor antagonism.