There are several kalkon derived compounds that have been tested for efficacy as antifungi, antibacterial, anticancer and antitumor that is compound 2-hydroxy kalkon and 2-hydroxy-4-dimethylamino kalkon. Both compounds are shown to have an effect as antifungal, antibacterial, anticancer and antitumor. Other derived kalkon derived compounds still have many benefits to other organs in the body. In 2016 a study of kalkon derived compounds 1-(2,5-dihydroxyphenyl)-(3-pyridine-2-yl) -propenone which is the synthesis of the starting material 2,5-dihydroxyacetophenone and pyridine 2- carbaldehyde is tested as a spasmolytic agent on ACh-M3 resptors and is shown to have a competitive antagonistic effect. The purpose of this study is to examine the effect of DHPP on the contraction of the isolated guinea pig ileum which is induced by Histamine. This research uses in vitro method by isolating guinea pig ileum using organ bath. Ileum is soaked in a tyrode buffer solution which is then treated. The doses used to test DHPP compounds were 10 μM and 20 μM. While the agonist is given with a series of levels of 10-8 - 10-2 M. In vitro test will also study the type of antagonists of DHPP compounds and their reversibility properties on receptors. The results showed that the compound DHPP can inhibit ileum muscle contraction induced isolated histamine. In receptors H1 shifts the value of pD2 significant (p <0.05) only in the group of compounds DHPP 20 μM. Value PD2 control group, the compound DHPP 10 μM and 20 μM respectively of 5,84; 5.54 and 5.49. From the analysis of Schild-plot known type of antagonism is competitive (slope: 0,853, pA2:1,650). The conclusion of this study is the compound DHPP have a competitive antagonist activity at the receptor H1.