Expert opinion on investigational drugs
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Expert Opin Investig Drugs · Jan 2012
ReviewImatinib mesylate for the treatment of pulmonary arterial hypertension.
Despite recent advances, pulmonary arterial hypertension (PAH) remains a devastating disease which harbors a poor prognosis. Novel therapeutic approaches directly targeting pulmonary vascular remodeling are warranted. ⋯ PDGF is a potent mitogen for pulmonary vascular smooth muscle cells and represents an important mediator of pulmonary vascular remodeling. Imatinib mesylate, a compound that inhibits the Bcr-Abl kinase and was developed for the treatment of chronic myeloid leukemia, also targets PDGF receptors. Both experimental and clinical data indicate that it reverses the vascular remodeling process even when it is fully established. Results from Phase II and III clinical trials suggest potent and prolonged efficacy in patients with severe PAH (i.e., pulmonary vascular resistance > 800 dynes*s*cm(-5)). Future studies should evaluate the long-term clinical efficacy and safety of imatinib, including patients with less impaired hemodynamics. Based on the current knowledge, this compound is likely to become an additional treatment option for patients with PAH and has the potential to at least partially correct the pathology of the disease.
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Expert Opin Investig Drugs · Jan 2012
ReviewInvestigational NMDA receptor modulators for depression.
With regards to depression, the role of N-methyl-D-aspartate receptor (NMDA) was pursued many years ago, mainly in the form of preclinical studies. Since then, there have been several clinical data in the literature indicating the efficacy of NMDA receptor antagonists of either stand-alone or as an adjunct therapy in depression and depression-related diseases. ⋯ Several NMDA receptor modulators have been tested in both human and animal studies to examine their potential antidepressant activity. Most of the compounds that exhibited beneficial properties in the animal tests and models of depression either have never been tested or did not show efficacy in humans. For some of them, such as ketamine, where a consistently reproducible antidepressant effect was found, clinical use is limited by a variety of adverse effects. However, ketamine has become a standard tool for identifying the biological factors associated with rapid antidepressant action and, as such, is a novel target for the development of new therapeutics.