Chemical differentiation of histamine H1- and H2-receptor agonists.
Histamine exists predominantly as the NT-H tautomer of the monocation (IIa) at a physiological pH of 7.4 and structure-activity studies indicate that this tautomer is likely to be the pharmacologically active species for both H1 and H2 receptors. Effective H2-receptor agonists appear to require a prototropic tautomeric system whereas H1-receptor agonists do not need to be tautomeric. This identifies a chemical difference in the receptor requirements which provides the basis for obtaining selective histamine H1-receptor agonists. Thus 2-(2-aminoethyl)thiazole and 2-(2-aminoethyl)pyridine are nontautomeric and are highly selective agonists for histamine H1 receptors (H1:H2 ca. 90:1 and 30:1, respectively). In conjunction with the selective H2-receptor agonist, 4-methylhistamine, they are of great value for studying the pharmacology of histamine receptors.
D000818:Animals; D005260:Female; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D006168:Guinea Pigs; D006632:Histamine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007536:Isomerism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D011955:Receptors, Drug; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship
D011955:Receptors, Drug; D006632:Histamine