Clinical Neuropharmacology 

About: Clinical Neuropharmacology is an academic journal published by Lippincott Williams & Wilkins. The journal publishes majorly in the area(s): Levodopa & Medicine. It has an ISSN identifier of 0362-5664. Over the lifetime, 3625 publications have been published receiving 78880 citations.

Acute spinal cord injury, part I: pathophysiologic mechanisms.

Abstract: Spinal cord injury (SCI) is a devastating and common neurologic disorder that has profound influences on modern society from physical, psychosocial, and socioeconomic perspectives. Accordingly, the present decade has been labeled the Decade of the Spine to emphasize the importance of SCI and other spinal disorders. Spinal cord injury may be divided into both primary and secondary mechanisms of injury. The primary injury, in large part, determines a given patient's neurologic grade on admission and thereby is the strongest prognostic indicator. However, secondary mechanisms of injury can exacerbate damage and limit restorative processes, and hence, contribute to overall morbidity and mortality. A burgeoning body of evidence has facilitated our understanding of these secondary mechanisms of injury that are amenable to pharmacological interventions, unlike the primary injury itself. Secondary mechanisms of injury encompass an array of perturbances and include neurogenic shock, vascular insults such as hemorrhage and ischemia-reperfusion, excitotoxicity, calcium-mediated secondary injury and fluid-electrolyte disturbances, immunologic injury, apoptosis, disturbances in mitochondrion function, and other miscellaneous processes. Comprehension of secondary mechanisms of injury serves as a basis for the development and application of targeted pharmacological strategies to confer neuroprotection and restoration while mitigating ongoing neural injury. The first article in this series will comprehensively review the pathophysiology of SCI while emphasizing those mechanisms for which pharmacologic therapy has been developed, and the second article reviews the pharmacologic interventions for SCI.

Mechanism of Action of Oral Fingolimod (FTY720) in Multiple Sclerosis

Abstract: Fingolimod (FTY720) is a first-in-class orally bioavailable compound that has shown efficacy in advanced clinical trials for the treatment of multiple sclerosis (MS). In vivo, fingolimod is phosphorylated to form fingolimod-phosphate, which resembles naturally occurring sphingosine 1-phosphate (S1P), an extracellular lipid mediator whose major effects are mediated by cognate G protein-coupled receptors. There are at least 5 S1P receptor subtypes, known as S1P subtypes 1-5 (S1P1-5), 4 of which bind fingolimod-phosphate. These receptors are expressed on a wide range of cells that are involved in many biological processes relevant to MS. S1P1 plays a key role in the immune system, regulating lymphocyte egress from lymphoid tissues into the circulation. Fingolimod-phosphate initially activates lymphocyte S1P1 via high-affinity receptor binding yet subsequently induces S1P1 down-regulation that prevents lymphocyte egress from lymphoid tissues, thereby reducing autoaggressive lymphocyte infiltration into the central nervous system (CNS). S1P receptors are also expressed by many CNS cell types and have been shown to influence cell proliferation, morphology, and migration. Fingolimod crosses the blood-brain barrier and may therefore have direct CNS effects, distinguishing it from immunologically targeted MS therapies. Prophylactic administration of fingolimod to animals with experimental autoimmune encephalitis (EAE), a model of MS, completely prevents development of EAE features, whereas therapeutic administration significantly reduces clinical severity of EAE. Therapeutic efficacy observed in animal studies has been substantiated in phase 2 and 3 trials involving patients with relapsing or relapsing-remitting MS.

Pharmacological mechanisms of opioid analgesics.

Abstract: The description of multiple classes of opioid receptors has had a major impact on our understanding of the mechanisms of analgesia. Three major classes of opioid receptors have been defined: mu, kappa, and delta. The mu receptors have been further subclassified into two distinct subtypes (mu 1 and mu 2), as have the delta receptors (delta 1 and delta 2). Kappa receptors have been subdivided into kappa 1, kappa 2, or kappa 3 subtypes. All of these subtypes modulate pain perception, with the exception of the kappa 2 receptor, which has not been adequately examined. Supraspinal systems have been described for mu 1, kappa 3, and delta 2 receptors while mu 2, kappa 1, and delta 1 receptors modulate pain at the spinal level. In addition to their ability to act independently, the various systems also interact synergistically with each other. Thus, the relief of pain involves the complex interaction of at least six receptor systems. This review discusses the implications of opiate receptor multiplicity on the control of pain.

The nighttime problems of Parkinson's disease.

Abstract: In a national survey conducted among 220 patients with Parkinson's disease (PD), 215 reported experiencing disabilities at night or on waking. The most common problems were inability to turn over or get out of bed and a frequent need to pass urine during the night. For the majority of patients, sleep was disrupted. Despite these difficulties, two-thirds of patients rated sleep quality as acceptable or good. The average duration of sleep was 6.5-7 h but approximately 8% of patients reported less than 5 h sleep per night. Hypnotic or sedative drugs were used by 29% of patients to help them sleep but only 6% took any antiparkinsonian medication during the night. Just over half the patients had told their doctor of nocturnal problems; prescription of hypnotic drugs or changes to antiparkinsonian therapy were the remedies most frequently tried. Problems at night are common in PD and, because of their debilitating effect on performance during the daytime, merit special attention.

Falls and Parkinson's Disease

Abstract: SummaryOne hundred patients with Parkinson's disease (PD) and five patients with progressive supranuclear palsy were questioned about the frequency, circumstances, and consequences of falling. Parkinsonian symptoms were scored using the unified rating scale. Thirty-eight percent of parkinsonian pati