Biomaterial Database

Dimaprit, (S-[3-(N,N-dimethylamino)propyl]isothiourea). A highly specific histamine H2-receptor agonist. Part 2. Structure-activity considerations. 1977

G J Durant, and C R Ganellin, and M E Parsons

Dimaprit, S-[3-(N,N-dimethylamino)propyl]isothiourea, appears to be a highly specific histamine H2-receptor agonist. Further indications of specificity are obtained from chemical considerations. Dimaprit has two basic centres (pKa values respectively 8.23 and 9.23, at 40 degrees) and at pH 7.4 about 5% of the molecules will be present as the monocation analogous to histamine monocation. Chemical comparison suggests that the --N+HMe2 group corresponds to the --N+H3 of histamine, and that the isothiourea group of dimaprit (which can undergo 1,3-prototropic tautomerism) may simulate the imidazole ring of histamine and function as a proton transfer agent at H2 receptors. Simple structural analogues of dimaprit are only weakly active, indicating a high degree of chemical specificity for H2-receptor stimulation; such compounds (e.g. the lower homologue, SK & F 91487) may serve as useful chemical controls when studying the actions of dimaprit.

UI	MeSH Term	Description	Entries
D007536	Isomerism	The phenomenon whereby certain chemical compounds have structures that are different although the compounds possess the same elemental composition. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)	Isomerisms
D011968	Receptors, Histamine	Cell-surface proteins that bind histamine and trigger intracellular changes influencing the behavior of cells. Histamine receptors are widespread in the central nervous system and in peripheral tissues. Three types have been recognized and designated H1, H2, and H3. They differ in pharmacology, distribution, and mode of action.	Histamine Binding Sites,Histamine Receptors,Histamine Receptor,Binding Sites, Histamine,Receptor, Histamine,Sites, Histamine Binding
D011970	Receptors, Histamine H2	A class of histamine receptors discriminated by their pharmacology and mode of action. Histamine H2 receptors act via G-proteins to stimulate ADENYLYL CYCLASES. Among the many responses mediated by these receptors are gastric acid secretion, smooth muscle relaxation, inotropic and chronotropic effects on heart muscle, and inhibition of lymphocyte function. (From Biochem Soc Trans 1992 Feb;20(1):122-5)	Histamine H2 Receptors,H2 Receptors,Receptors, H2,H2 Receptors, Histamine
D006632	Histamine	An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.	Ceplene,Histamine Dihydrochloride,Histamine Hydrochloride,Peremin
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013890	Thiourea	A photographic fixative used also in the manufacture of resins. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance may reasonably be anticipated to be a carcinogen (Merck Index, 9th ed). Many of its derivatives are ANTITHYROID AGENTS and/or FREE RADICAL SCAVENGERS.