The anxiolytic and analgesic properties of fenobam, a potent mGlu5 receptor antagonist, in relation to the impairment of learning

Allosteric Modulation of Family C G-Protein-Coupled Receptors: from Molecular Insights to Therapeutic Perspectives

“…These effects were not seen in mGlu5 receptor knockout mice. The beneficial effects of fenobam, however might, be limited by a lack of therapeutic window (Jacob et al, 2009). Apparently successful phase II clinical trials with the negative allosteric mGlu5 receptor modulator ADX10059 (Bolea et al, 2004) in the indication migraine have been summarized by Jaeschke et al (2008) and by Gasparini et al (2008).…”

Effects of mGluR5 positive and negative allosteric modulators on brain damage evoked by hypoxia-ischemia in neonatal rats

“…As pharmacological tools we used fenobam and ADX47273, which are selective mGluR5 negative and positive allosteric modulators, respectively [16,25]. Oral fenobam administration in adult rats (10-30 mg/kg) exerted analgesic and anxiolytic-like effects and impaired learning [13], whereas the behavioral effects of ADX47273 were observed in rats treated with 10 and 30 mg/kg i.p. [16].…”

“…Fenobam is a selective negative allosteric modulator of mGluR5, with anxiolytic and analgesic properties [13,25]. Recently mGluR5 PAMs emerged as a new group of drugs that may potentiate NMDAR-mediated currents by utilizing the functional coupling between mGluR5 and NMDARs [6].…”

Brain concentrations of mGluR5 negative allosteric modulator MTEP in relation to receptor occupancy – Comparison to MPEP

“…This does not seem to be 342 a general feature of mGluR5 NAMs as for MPEP this factor was 12 343 (but note that only in vitro recovery data are available). Similarly, 344 fenobam, another mGluR5 NAM seems to reach in the 345 brain concentrations of 650 nM after behaviorally active dose of 346 30 mg/kg po [29], which is around 10 times higher than the affinity 347 for the receptor (60-70 nM) [30]. 348 While microdialysis methods do not measure levels at the 349 synapse, they do seem to provide an index of the unbound fraction 350 that presumably is available to interact directly at the target.…”