New anxiolytics in development.
Benzodiazepines (BDZ), the most popular drug of choice for treating anxiety disorders, present side-effects such as sedation, muscular disorders, abuse liability and synergistic effect with alcohol and CNS depressant drugs. At present, pharmacological research is focusing to find anxiolytic drugs as efficacious as benzodiazepines but without side-effects. This review reports the status of the pharmaceutical research and development on novel drugs for the treatment of anxiety disorders. A close analysis of the items selected by the N5C "Pharmaprojects" search (anxiolytic class) yielded the following classification: A) Drugs interacting with the GABA-A receptor complex, which includes BDZ-like drugs, partial BDZ agonists (beta-carbolines) and drugs interacting with the GABA-A complex through an as yet unidentified mechanism (15 compounds), B) Drugs acting as CCK-B antagonists (5 compounds), C) Drugs interacting with serotonergic function (30 compounds) subdivided into: (i) agonists at the 5-HT1A receptor, (ii) antagonists at the 5-HT2 receptor, and (iii) antagonists at the 5-HT3 receptor; D) Drugs with other mechanisms (22 compounds). Based on these results, it is not possible to identify a common mechanism through which the selected drugs under development exert their anxiolytic effect. Therefore, it appears that different biological mechanisms are specifically involved in the different anxiety disorders.
Mosconi
M
M
Medical Directorate, Glaxo, Verona, Italy.
Chiamulera
C
C
Recchia
G
G
D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000188:drug therapy*; D001569:Benzodiazepines; D002986:Clinical Trials as Topic; D006801:Humans; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D011963:Receptors, GABA-A / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*
D014151:Anti-Anxiety Agents; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D011963:Receptors, GABA-A; D011985:Receptors, Serotonin; D001569:Benzodiazepines