Back to Search
Start Over
Effects of Impromidine- and Arpromidine-Derived Guanidines on Recombinant Human and Guinea Pig Histamine H1 and H2Receptors
- Source :
- Archiv der Pharmazie. 340:9-16
- Publication Year :
- 2007
- Publisher :
- Wiley, 2007.
-
Abstract
- Imidazolylpropylguanidines derived from impromidine and arpromidine are more potent and efficacious agonists at the guinea pig histamine H2 receptor (gpH2R) than at the human H2R (hH2R) in the GTPase assay. Additionally, such guanidines are histamine H1 receptor (H1R) antagonists with preference for the human relative to the guinea pig receptor. The purpose of this study was to examine structure-activity relationships of guanidines at human and guinea pig H1R and H2R species isoforms expressed in Sf9 insect cells. Three impromidine analogues and six arpromidine analogues exhibited agonistic activity at H2R and antagonistic activity at H1R as assessed in the steady-state GTPase assay. Species selectivity of derivatives was similar as compared with the parent compounds. None of the structural modifications examined (different aromatic ring systems and different ring substituents) was superior in terms of H2R potency and efficacy relative to impromidine and arpromidine, respectively. These data point to substantial structural constraints at the agonist binding site of H2R. Guanidines exhibited distinct structure-activity relationships for H1R antagonism in a radioligand competition binding assay and the GTPase assay and for H1R inverse agonism. Our data indicate that it is difficult to obtain guanidine-type agonists with high potency and high efficacy for hH2R, but those compounds may be useful tools for exploring the antagonist binding site and constitutive activity of H1R.
- Subjects :
- Agonist
Insecta
medicine.drug_class
Recombinant Fusion Proteins
Guinea Pigs
Pharmaceutical Science
Histamine H1 receptor
Pharmacology
Transfection
Binding, Competitive
Guanidines
01 natural sciences
Cell Line
GTP Phosphohydrolases
Histamine Agonists
Guinea pig
Structure-Activity Relationship
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Impromidine
Histamine H2 receptor
Drug Discovery
GTP-Binding Protein alpha Subunits, Gs
medicine
Radioligand
Animals
Humans
Receptors, Histamine H2
Receptors, Histamine H1
030304 developmental biology
Pyrilamine
0303 health sciences
Molecular Structure
010405 organic chemistry
Chemistry
Ligand binding assay
Imidazoles
General Medicine
0104 chemical sciences
3. Good health
010404 medicinal & biomolecular chemistry
Biochemistry
030220 oncology & carcinogenesis
Histamine H1 Antagonists
GTP-Binding Protein alpha Subunits, Gq-G11
Histamine
medicine.drug
Subjects
Details
- ISSN :
- 15214184 and 03656233
- Volume :
- 340
- Database :
- OpenAIRE
- Journal :
- Archiv der Pharmazie
- Accession number :
- edsair.doi.dedup.....3740fb47dc0f0bb3dd0fdb80dc9a4d54