CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Volume 9, Issue 1, 2010

Drug delivery to the central nervous system remains a vexing problem because of the presence of the blood-brain barrier (BBB), whose endothelial cell tight junctions limit the paracellular flux of hydrophilic molecules. One solution may be vector-mediated delivery to the brain. This employs chimeric peptide technology, wherein the drug is conjugated to a molecular carrier of protein nature (e.g. cationized albumin or a transf Read More

Alcoholism and other alcohol use disorders are major public health problems, and the success rates of non-pharmacological treatment of these disorders such as psychotherapy, cognitive-behavioral therapy, group therapy, or residential treatment programs, remain only modest at best. High rates of recidivism (relapse) in alcoholics attempting to remain abstinent are prevalent worldwide. In recent years abundant eviden Read More

Disulfiram treatment, despite its limitations, remains a viable option as a treatment for alcohol dependence and has shown recent promise in treating (1) those with co-morbid alcohol dependence and post-traumatic stress disorder, (2) those with co-morbid cocaine- and alcohol-dependence, and (3) those with cocaine-dependence alone. Although disulfiram's mechanism of action in alcohol dependence was long Read More

Naltrexone is an opioid receptor antagonist with established efficacy, albeit moderate, for the treatment of alcohol dependence. This manuscript provides a critical review of the literature on naltrexone as a pharmacotherapy for alcoholism by covering the following areas: (a) clinical findings from treatment studies; (b) pharmacokinetics and safety data; (c) medication compliance and persistence; and (d) neurobiological and b Read More

Alcoholism is one of the most prevalent substance dependence disorders in the world. Advances in research in the neurobiological mechanisms underlying alcohol dependence have identified specific neurotransmitter targets for the development of pharmacological treatments. Acamprosate, marketed under the brand name Campral, is an orally administered drug available by prescription in the U.S. and through Read More

Both preclinical and clinical research studies have shown the GABAB receptor agonist baclofen represents a promising treatment for alcohol dependence. Preliminary clinical studies indicate that baclofen is able to suppress withdrawal symptoms in alcoholdependent patients affected by the alcohol withdrawal syndrome. Moreover, baclofen has shown efficacy and safety in promoting alcohol abstinence in alcohol depende Read More

Alcohol dependence is a major health problem worldwide. Various pharmacological agents have been used in the management of alcohol dependence. This review looks at the role of topiramate and other anticonvulsants in the management of alcohol dependence. Topiramate is the most widely used anticonvulsant in the treatment of alcohol dependence. The literature on topiramate is reviewed and critically analyze Read More

Alcohol dependence is a costly and socially devastating illness. The dopamine system has received increased attention due to the consensus that dopaminergic dysfunction is at the core of the addiction process. Agents that modulate this system might be beneficial in reducing craving, reward, and relapse. Aripiprazole is a 3rd generation atypical antipsychotic U.S. Food and Drug Administrationapproved for the treatment of schi Read More

The present paper summarizes the results of a number of pharmacological studies implicating the cannabinoid CB1 receptor in the neural circuitry regulating different alcohol-related behaviors in rodents. Specifically, cannabinoid CB1 receptor antagonists - including the prototype, rimonabant - have been reported to suppress: (a) acquisition and maintenance of alcohol drinking behavior under the 2-bottle “alcohol vs water” choi Read More

Alcohol use disorders (AUDs) are complex and developing effective treatments will require the combination of novel medications and cognitive behavioral therapy approaches. Epidemiological studies have shown there is a high correlation between alcohol consumption and tobacco use, and the prevalence of smoking in alcoholics is as high as 80% compared to about 30% for the general population. Both preclinical and clinica Read More

Alcoholism is a chronic disorder characterized by cycling periods of excessive ethanol consumption, withdrawal, abstinence and relapse, which is associated with progressive changes in central corticotropin-releasing factor (CRF) receptor signaling. CRF and urocortin peptides act by binding to the CRF type 1 (CRF1R) or the CRF type 2 (CRF2R) receptors, both of which have been implicated in the regulation of neurobiological res Read More

Nociceptin (known also as orphanin FQ) is the most recently discovered member of the endogenous opioid peptide family, albeit nearly 15 years ago. Nociceptin renders or influences many behavioral, psychological and neurobiological processes, including memory, anxiety, stress and reward. Since its discovery, results of a steady stream of studies have suggested that endogenous nociceptin might be involved in responses to Read More

Calcium is an essential intracellular messenger and serves critical cellular functions in both excitable and non-excitable cells. Most of the physiological functions in these cells are uniquely regulated by changes in cytosolic Ca2+ levels ([Ca2+]i), which are achieved via various mechanisms. One of these mechanism(s) is activated by the release of Ca2+ from the endoplasmic reticulum (ER), followed by Ca2+ inf Read More

Mitochondrial metabolism is a highly orchestrated phenomenon in which many enzyme systems cooperate in a variety of pathways to dictate cellular fate. As well as its vital role in cellular energy metabolism (ATP production), mitochondria are powerful organelles that regulate reactive oxygen species production, NAD+/NADH ratio and programmed cell death. In addition, mitochondrial abnormalities have been well-reco Read More

The active form of the serine/threonine kinase cRaf-1 is upregulated postmortem in the brains of Alzheimer's disease (AD) patients and in transgenic mouse models of AD pathology. The persistent activation of cRaf-1 can activate the proinflammatory factor NFκB and consequently, upregulate the expression of several of its downstream factors such as the amyloid precursor protein (APP), Cox-2 and iNOS. These fact Read More