N-Methyldimaprit (SK&F92054). A chemical control for the histamine H2-receptor agonist dimaprit.

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.

Icotidine, an antagonist of histamine at both H1 and H2 receptors.

SK&F 93319 (icotidine), 2-[4-(3-methoxypyrid-2-yl)butylamino]-5-[(6-methylpyrid-3-yl )-methyl]- pyrimidin-4-one trihydrochloride, has been identified as a novel agent which combines into one molecule the ability to antagonize the actions of histamine at H1 and H2 receptors across a similar concentration or dose range. The degree of antagonism of vascular responses to histamine exceeds that possible with either an H1- or H2-receptor histamine antagonist alone. SK&F 93319 may have therapeutic utility in conditions requiring simultaneous antagonism of histamine at H1 and H2 receptors.