Expert opinion on therapeutic targets
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Present treatment of medulloblastoma, the most common malignant brain tumor in children, includes surgery, radiotherapy and chemotherapy. In spite of radical treatment, only about 70% of patients survive. Also side effects of the treatment are severe, mostly due to applied radiotherapy. ⋯ The quest for a better treatment modalities includes better risk stratification methods, including molecular profiling of individual tumors and a search for new small molecules capable of inhibiting hyperactive signaling pathways. Several candidates for such agents are being tested presently.
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Expert Opin. Ther. Targets · Sep 2007
ReviewNovel migraine therapy with calcitonin gene-regulated peptide receptor antagonists.
Primary headaches, for example, migraine and cluster headaches represent the most prevalent neurological disorders, affecting up to 15-20% of the adult population. There is a clear association between head pain and the release of calcitonin gene-related peptide (CGRP). In this review the role of CGRP in human cranial circulation is described and the role for specific CGRP antagonism elucidated. ⋯ The central role of CGRP in migraine pathophysiology has resulted in the development of small-molecule CGRP antagonists with no cardiovascular side effects. Such compounds have high selectivity for human CGRP receptors and are efficacious in the relief of acute migraine attacks. Research indicates that they effect the abluminal side of the blood-brain barrier and that they are not vasoconstrictive, providing a new dimension in therapy.
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Neuropathic pain remains a large unmet medical need. A number of therapeutic options exist, but efficacy and tolerability are less than satisfactory. ⋯ Several sodium channel subtypes are expressed primarily in sensory neurons and may contribute to the efficacy of sodium channel blockers. In this report, the authors review the current understanding of the role of sodium channels and of specific sodium channel subtypes in neuropathic pain signaling.
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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.