Abstract
Antagonism of the bradykinin B(1) receptor was demonstrated to be a potential treatment for chronic pain and inflammation. Novel benzodiazepines were designed that display subnanomolar affinity for the bradykinin B(1) receptor (K(i) = 0.59 nM) and high selectivity against the bradykinin B(2) receptor (K(i) > 10 microM). In vivo efficacy, comparable to morphine, was demonstrated for lead compounds in a rodent hyperalgesia model.
MeSH terms
-
Animals
-
Benzodiazepines / chemical synthesis*
-
Benzodiazepines / chemistry
-
Benzodiazepines / pharmacology
-
Bradykinin Receptor Antagonists*
-
CHO Cells
-
Cricetinae
-
Humans
-
Hyperalgesia / chemically induced
-
Hyperalgesia / drug therapy
-
Radioligand Assay
-
Rats
-
Rats, Sprague-Dawley
-
Receptor, Bradykinin B1
-
Receptor, Bradykinin B2
-
Structure-Activity Relationship
Substances
-
Bradykinin Receptor Antagonists
-
Receptor, Bradykinin B1
-
Receptor, Bradykinin B2
-
Benzodiazepines