Potential histamine H2-receptor antagonists. 3. Methylhistamines.
Syntheses are described for all the mono- and some di- and trimethylhistamines. New methods are given for the known Npi, Ntau-, Nalpha-, 2-, and 4-methylhistamines and for the novel compounds, beta-methyl-, 4,Nalpha-dimethyl-, and 4,Nalpha,Nalpha-trimethylhistamines. Agonist activities are reported for stimulation of histamine H1 (guinea-pig ileum) and H2 (rat gastric acid secretion) receptors. H2-Receptor agonist activities indicate that a methyl group is more readily accommodated at the 4 and Nalpha positions than elsewhere in the histamine molecule and that receptor binding is substantially retained with a methyl substituent in these positions. Thus, for the design of potential antagonists, two sites are identified as being worthwhile exploring for the introduction of lipophilic substituents.
D000818:Animals; D001665:Binding Sites; D005750:Gastric Juice / Q000378:metabolism; D006168:Guinea Pigs; D006632:Histamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis*; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008745:Methylation; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D011955:Receptors, Drug
D006634:Histamine H1 Antagonists; D011955:Receptors, Drug; D006632:Histamine