Current Topics in Medicinal Chemistry - Volume 16, Issue 29, 2016

Schizophrenia is a chronic and debilitating neuropsychiatric disorder affecting approximately 1% of the world’s population. This disease is associated with considerable morbidity placing a major financial burden on society. Antipsychotics have been the mainstay of the pharmacological treatment of schizophrenia for decades. The traditional typical and atypical antipsychotics demonstrate clinical efficacy in treating positi Read More

Glycine acts as an inhibitory neurotransmitter at glycine receptor (GlyR)-enriched synapses and as an obligatory co-agonist at the N-methyl-D-aspartate (NMDA) receptor, where it facilitates neuronal excitation. Two high-affinity and substrate selective transporters, glycine transporter-1 and glycine transporter-2 (GlyT-1 and GlyT-2), regulate extracellular glycine concentrations within the CNS and as such, play critical roles in Read More

The orexin receptors OX1 and OX2 play important roles in the regulation of sleep-wake cycles, feeding, reward and energy homeostasis. Since these G protein-coupled receptors were deorphanised in 1998, more than 200 patents containing orexin receptor antagonists have been filed and, in 2014, suvorexant (Belsomra®) became the first of these compounds to receive approval from the FDA. Suvorexant is a dual orexin re Read More

In the last ~30 years, scientists have made great strides in understanding the biological function of group I metabotropic glutamate receptors (mGlu) in health and disease, as well as developing a broad array of potent and selective agents able to activate or inhibit these receptors. This article provides a comprehensive review of the most recent group I mGlu modulators published in patent and non-patent literatures fro Read More

Phosphodiesterases (PDEs) have gained attention as potential pharmacological targets for neuropsychiatric diseases due to their ability to hydrolyze the second messengers, cGMP and/or cAMP. It is well-known the relationship between cAMP signaling and inflammation. Since neuroinflammation is considered to play an important role in the pathology of brain disorders, inhibition of PDEs highly expressed in brai Read More

The neurotransmitter glutamate and its receptors have long been of interest to scientists involved in pharmaceutical research since dysfunction of the glutamatergic signalling pathway has been associated with the pathophysiology of several psychiatric and neurological disorders. The research on AMPAR positive allosteric modulators offers opportunities to modulate fast excitatory synaptic transmission and identify new potential Read More