Novel non-benzodiazepine anxiolytics

Fenobam: A Clinically Validated Nonbenzodiazepine Anxiolytic Is a Potent, Selective, and Noncompetitive mGlu5 Receptor Antagonist with Inverse Agonist Activity

“…Fenobam was active in a comparable dose range after oral administration in all tests (MED 10 -30 mg/kg p.o.). These data confirm the previously reported preclinical studies with fenobam (i.e., rat conflict tasks including Geller-Seifter and Vogel) (Patel et al, 1982;Goldberg et al, 1983). The data are also in line with previous findings with selective mGlu5 receptor antagonists, particularly the prototypical mGlu5 receptor antagonist MPEP (for review, see Spooren et al, 2001).…”

“…Interestingly, fenobam (McN-3377) was originally developed as a nonbenzodiazepine anxiolytic (by McNeil Laboratories, 1978, with an unknown molecular target. In preclinical studies, fenobam is reported to be active in rat models of anxiety (conflict tasks including Geller-Seifter and Vogel) (Patel et al, 1982), and this activity was not blocked by a benzodiazepine antagonist (Goldberg et al, 1983).…”

Anticonflict Action of Tandospirone in a Modified Geller-Seifter Conflict Test in Rats.

“…For example, in rat conflict tests, which are the most widely used animal behavioral para digms for recognizing potential anxiolytic drug activity, some groups, including our own, were able to demonstrate anticonflict activities of azapirones (5,(12)(13)(14), while others failed to find any positive effects (15)(16)(17). Moreover, in the former cases, the efficacies of azapir ones were substantially lower than those of benzodiazepines.…”

Behavioral analysis of zopiclone on the basis of their discriminative stimulus properties in the rat.

“…From this point, it is pos sible to consider that the zopiclone stimulus is related to an anxiolytic activity. However, the pyrazolopyridine derivative tracazolate, which has an anxiolytic profile in a punished drinking test (20,21), failed to generalize to the zopiclone stimulus. In binding studies, tracazolate increased the affinity of benzo diazepines for their binding sites, probably through an action at the picrotoxin site (20).…”