title: N-Methyldimaprit (SK&F92054). A chemical control for the histamine H2-receptor agonist dimaprit.
abstract: Dimaprit analogues having alkyl substituents on the isothiourea group have no detectable H2-agonist activity on the guinea-pig atrium. N-Methyldimaprit [S-[3-(N,N-dimethylamino)propyl]-N'-methylisothiourea] (SK&F92054) is identified as a compound which may serve as a suitable chemical control when studying the actions of dimaprit at putative H2-histamine receptors. Concentrations of N-methyl-dimaprit (up to 3 X 10(-3) M) had no agonist activity in vitro on the guinea-pig atrium (less than 0.005% of the activity of histamine), rat uterus (up to 2 X 10(-3) M,) or as a stimulant of guinea-pig ventricular adenylate cyclase (up to 10(-3) M). N-Methyldimaprit at 10(-3) M also did not significantly stimulate acid secretion in the rat isolated stomach preparation; it was a very weak stimulant of gastric acid secretion (less than 0.2% of the activity of histamine) in vivo in the lumen-perfused stomach of the anaesthetised rat but exhibited marked tachyphylaxis on repeated administration. N-Methyldimaprit has two basic centres, macroscopic pKa values 8.31 and 9.58 at 40 degrees C.
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D011970:Receptors, Histamine H2 / Q000187:drug effects*; D013859:Thiocarbamates / Q000494:pharmacology*
chemical_list: D011970:Receptors, Histamine H2; D013859:Thiocarbamates; C043202:N-methyldimaprit; D006632:Histamine; D000262:Adenylyl Cyclases