Characterization of an accessory binding area in the histamine H2 receptor.
The histamine H2 receptor-blocking activity of ranitidine and lamtidine analogues has been investigated to gain information on the structure of the receptor area adjacent to the site fitted by the polar group. The introduction of differently shaped alkyl moieties on the polar group is always accompanied by maintenance or by an increase of H2 receptor antagonism with respect to the starting lead compound (KB on guinea-pig isolated atria ranging from 49 nM to 1.5 nM). The results seem to indicate the presence in the histamine H2 receptor of an area of a predominantly hydrophobic nature located at the boundary of the site fitted by the polar group.
Institute of Pharmacology and Pharmacognosy, Pharmacy School, University of Turin, Italy.
M
M
Orsetti
G
G
Sorba
D000818:Animals; D001665:Binding Sites; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002927:Cimetidine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011899:Ranitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D011970:Receptors, Histamine H2 / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000494:pharmacology
D006635:Histamine H2 Antagonists; D010880:Piperidines; D011970:Receptors, Histamine H2; D014230:Triazoles; D002927:Cimetidine; D011899:Ranitidine; C038304:lamtidine; C023990:tiotidine