Expert opinion on therapeutic targets
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After a 12-year search for the antipsychotic receptor, the binding site was discovered and labelled by [3H]haloperidol in 1975. Of the various neurotransmitters, dopamine was the most potent in inhibiting the binding of [3H]haloperidol, indicating that the antipsychotic receptor was a dopamine receptor, now named the dopamine D2 receptor, a major targeting site in schizophrenia. ⋯ Antipsychotics that elicit low or no Parkinsonism or prolactinaemia are loosely attached to D2 and rapidly dissociate from D2, whereas those eliciting Parkinsonism stay tightly attached to D2 for many hours. Because animal models of psychosis (amfetamine sensitisation, brain lesions) all show a marked elevation in the number of high-affinity states of D2, the antipsychotics are thought to specifically target these D2High states in psychosis in general and schizophrenia in particular.
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Expert Opin. Ther. Targets · Jun 2006
ReviewTargets for deep brain stimulation in Parkinson's disease.
The use of stimulation electrodes implanted in the brain to control severely disabling neurological and psychiatric conditions is an exciting and fast emerging area of neuroscience. An excellent example is Parkinson's disease (PD), in which tens of thousands of patients have now been implanted with stimulation electrodes. Patients with PD underwent deep brain stimulation (DBS) at the level of the thalamus, globus pallidus internus, subthalamic nucleus, pedunculopontine nucleus and prelemniscal radiation. ⋯ Clinicians can choose their DBS target based on the situation of their individual PD patients. In the authors' opinion, patient-specific targeting should be preferred over disease-specific targeting. In this review, the authors give an overview of the targets that have been used for DBS in PD and discuss patient-specific targeting.
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Expert Opin. Ther. Targets · Jun 2006
Current targets in irritable bowel syndrome: an interview with Eamonn Quigley. Interview by Emma Quigley.
Eamonn M M Quigley, MD, FACG, is Vice-President of the World Gastroenterology Organisation and Secretary of the American College of Gastroenterology. He is also Professor of Medicine and Human Physiology and Head of the Medical School at the National University of Ireland in Cork. Between 1991 and 1998, he served as Chief of Gastroenterology and Hepatology at the University of Nebraska Medical Center, where he was also Professor in the Department of Internal Medicine. ⋯ His MD thesis was awarded by the National University of Ireland in 1984 and he received his medical education at University College Cork, graduating MB BCh BAO in 1976. Dr Quigley served as Editor-in-Chief of the American Journal of Gastroenterology from 1997 to 2003, and he has published > 400 articles, including original manuscripts, editorials, review articles, book chapters and case reports. He is also interested and involved in education in the area of gastroenterology and has participated in, or directed symposia, workshops and other teaching forums and prepared a variety of related teaching aids.
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Expert Opin. Ther. Targets · Feb 2006
A new therapeutic target for atherosclerosis treatment: interview with Uday Saxena. Interviewed by Emma Quigley.
Uday Saxena was appointed Chief Scientific Officer at Dr Reddy's Laboratories in 2000. In this role he provides the leadership and general strategy for the company's drug discovery research into metabolic disorders, cardiovascular disorders, inflammation, cancer and anti-infectives. He is also a member of the company's Senior Management Council. ⋯ On completing his postdoctoral fellowship at Colombia University, he went onto work on various drug discovery projects as Senior Scientist and Principal Research Scientist at Parke-Davis Warner-Lambert and as Director and Vice-President for preclinical research at AtheroGenics, Inc., before undertaking his current position. Uday Saxena has written over 50 peer-reviewed articles and invited reviews. He is currently on the Editorial Board of two international drug discovery-related journals including Expert Opinion on Therapeutic Targets.
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Expert Opin. Ther. Targets · Aug 2005
ReviewThe ERK/MAPK pathway, as a target for the treatment of neuropathic pain.
Peripheral nerve injury produces neuropathic pain as well as phosphorylation of mitogen activated protein kinase (MAPK) family in dorsal root ganglia (DRG) and dorsal horn. Following nerve injury, phosphorylation of extracellular signal-regulated protein kinase (ERK), an important member of this family, is sequentially increased in neurons, microglia and astrocytes of the dorsal horn and gracile nucleus, and in injured large DRG neurons. ⋯ In several animal models of neuropathic pain, MEK inhibitors, known to suppress the synthesis of ERK, have proven effective to alleviate pain at various time points. Thus, the regulation of ERK/MAPK can be considered as a promising therapeutic target for the treatment of neuropathic pain.