Glutamate receptors in the therapy of schizophrenia

Brain dopamine receptors appear to play a major role in the control of many diseases of the central nervous system (CNS), including schizophrenia. Drugs developed on the basis of dopamine hypothesis had beneficial effects, but did not cure schizophrenia or control the cognitive domain of the disease. The search for new appoaches to the treatment of  psychosis led to the hypothesis that glutamate receptors may be involved in the pathogenesis of some psychiatric diseases. Dr. Darryle Schoepp, Merck & Co, strongly supported this approach. In a videointerview with Dr. Greg Rose (see below) Dr.  Darryle Schoepp  discusses possible role of glutamate receptors in schizophrenia and proposes the development of glutamate agonists for treatment of psychosis.

Keywords:  CNS diseases; schizophrenia, psychosis, dopamine receptors, glutamate receptors, cognition domain, glutamate agonists, Dr. Darryle Schoepp; Merck & Co.; Dr. Greg Rose.

GABA-B and other brain receptors as drug targets

The development of new drugs for the therapy of central nervous system (CNS) diseases  often involves identification of specific receptors for ligands thought to be involved in the pathogenesis of a disease and
search for drugs capable of modulating ligand-receptor interaction.  This approach was supported by findings that some older CNS drugs modulate binding of  neurotransmitters to their receptors.  The hope was that by improving specificity and selectivity of ligands for their receptors new and better drugs to treat CNS diseases can be found.  This approach led to a few successful CNS drugs, but failed
to cure or significantly modify the progression of Alzheimer's (AD), Parkinson's (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), schizophrenia and other major CNS diseases.  It appears that these diseases do not involve abnormal interaction of neurotransmitters with their receptors or that they are multifactorial and a ligand selective for one receptor subtype may not always represent the best approach
to the therapy of these diseases. In the videointerview witrh Dr. Greg Rose (see below)
Sam J. Enna, Professor of Molecular and Interegrative Physiology at the University of Kansas School of Medicine discusses the role of  gamma-aminobutyric acid (GABA-B) and other brain receptors in the therapy of CNS diseases.
Keywords: Gamma-aminobutyric acid (GABA); GABA-B receptors; CNS diseases; baclofen, analgesics, muscle relaxants, antidepressants; cognition enhancement; beta-adrenoceptors in CNS; muscarinic receptors, multifactorial diseases;  dimerization of the receptors; GABA-B receptors subtypes; MS; ALS; Dr. Sam J, Enna; Dr. Greg Rose.

Sodium channels as targets for drugs to treat pain

There is an urgent need to find better drugs to treat pain.  Non-steroidal antiinflammatory drugs (NSAIDs) are not effective in all types of pain and their use is limited by side effects, including gastric ulcers and cardiovascular complications. Among the side effects of opioids (e.g. morphine, codeine, nalorphine) are respiratory depressioin, vomiting, constipation and hypotension. During the last decade brain sodium channels were found to be involved in the mediation of pain and are likely to be useful targets for novel analgesic drugs. In the videointerview with Dr. Greg Rose (see below) Dr. Stephen G. Waxman,  Professor and Chairman of Neurology at Yale University School of Medicine describes potential value of selective sodium channel antagonists as analgesics and his research in this area.

Keywords: NSAIDs, pain, modulation of pain, pain sensation, analgesics, sodium channels, erythromelalgia,
PEPD, familial rectal pain, neuropathic pain, phantom pain, sodium channel subtypes, NaV1.7, NaV1.8, NaV1.3, sodium channel antagonists.

TGFbeta and Alzheimer's disease

Dr. Richard A. Flavell, Professor of Immunobiology at Yale University School of Medicine,, suggested that cytokine TGFbeta (transforming growth factor beta) could be a target for new drugs to treat Alzheimer's disease (AD). In the following video Dr. Flavell is being interviewed by Dr. Harold Stern, Associate Clinical Professor of Surgery, Yale University School of Medicine, about possible role of TGFbeta in  AD.

Keywords: TGFbeta; Alzheimer's disease; AD; TGFbeta antibodies; TGFbeta antagonists; Richard A. Flavell; Yale Immunobiology; Harold Stern; Targets for antiAlzheimer drugs

AMPA receptors as targets for neuroprotective or antidepressant drugs

AMPA receptors are ionotropic transmembrane receptors for glutamate that mediate synaptic transmission in the brain. The name AMPA is derived from alpha-Amino-3-hydroxy-5-Methyl-4-isoxazole Propionic Acid that binds to these receptors. The principal ion gated by AMPA receptors is sodium. Because of their important role in the synaptic transmission AMPA receptors are viewed as likely targets  for new neuroprotective and/or antidepressant drugs. Dr. Michael Spedding from Servier Laboratories in France worked extensively with drugs affecting AMPA receptors. In the video interview with Dr. Greg Rose (see below) he points out that neuroprotection can result from either blockade or stimulation of AMPA receptors.
Keywords:  drug targets, drug receptors, AMPA receptors, AMPA, neuroprotection, neuroprotective drugs, antidepressants, synaptic transmission, glutamate, Michael Spedding, Greg Rose, Servier Laboratories