Chemical differentiation of histamine H1- and H2-receptor agonists.
J Med Chem, 1975/9;18(9):905-9.
Durant GJ, Ganellin CR, Parsons ME
PMID: 240025
Impact factor: 8.039
Abstract
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.
MeSH terms
Animals; Female; Gastric Juice; Gastric Mucosa; Guinea Pigs; Histamine; Hydrogen-Ion Concentration; Ileum; In Vitro Techniques; Isomerism; Male; Muscle Contraction; Muscle, Smooth; Rats; Receptors, Drug; Stimulation, Chemical; Structure-Activity Relationship
More resources
EndNote: Download