Novel anxiolytics that act as partial agonists at benzodiazepine receptors.
Benzodiazepines in clinical use have a range of pharmacological activities. Some, e.g. sedation, tolerance and addiction, are not welcome. Undesirable side-effects of drugs are often controlled by developing compounds that bind more selectively to one particular receptor subtype. An alternative approach, discussed here by Willy Haefely and colleagues, is the development of partial agonists which exploit regional differences in receptor reserve to tease apart biological responses. Partial agonists for the benzodiazepine modulatory site on the GABAA complex have been developed and their pharmacological profiles can be interpreted to suggest that neurons mediating anticonvulsant and anti-anxiety effects do indeed have a higher receptor reserve than neurons mediating other unwanted effects. This suggests that benzodiazepine receptor partial agonists may have important therapeutic potential.
Haefely
W
W
Pharmaceutical Research Department, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Martin
J R
JR
Schoch
P
P
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D002998:Clonazepam / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects*
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D002243:Carbolines; D007093:Imidazoles; D011725:Pyridines; D011963:Receptors, GABA-A; D002998:Clonazepam; C052036:alpidem; C062769:abecarnil; C054626:bretazenil