Psychiatry and Central Nervous System

Neboglamine is a first-in-class functional positive modulator of NMDA receptors with potent and selective inhibitory activity of noradrenalin reuptake. The compound has completed different Phase I clinical studies and a large Phase IIb trial has been designed as proof of concept for testing its therapeutic effect in schizophrenia. In this disease, the compound may represent a new generation antipsychotic specifically effective on negative, cognitive and mood symptoms. Other target indications that will be explored include drug abuse, major depression and dementias. Extensive research in the NMDA receptor area also led to the discovery of NMDA receptor antagonists with IL-6 release inhibitory properties, whose development is being considered for Alzheimer’s disease and Parkinson disease.

Itriglumide (CR 2945) is a selective antagonist of the CCK-2 receptor, which plays a regulatory role at both the gastrointestinal and Central Nervous System (CNS) levels. In the CNS, it has been postulated that CCK-2 activity may be implicated in the pathogenesis of anxiety disorders, for which itriglumide may therefore represent an innovative treatment strategy targeted to generalized anxiety and panic attacks, as postulated in numerous preclinical studies. The compound is undergoing Phase II clinical trials.

CR4056 is a novel imidazoline (I2) low affinity ligand endowed with potent analgesic activities in different animal models related to inflammatory, neurogenic and neuropathic pain. Preclinical development is almost completed in preparation for Phase I clinical studies to develop the compound in neuropathic pain. And acute non-specific pain states. Other analgesics that are specific sodium channel blockers are also under development. Finally, a series of orexin receptor antagonists are in exploratory development for use in anxiety disorders, compulsivity and sleep disorders. Orexins are neuro-hormones involved in the mechanisms of arousal.