Current Pharmaceutical Design - Volume 22, Issue 14, 2016

The frequency of neuropsychiatric disorders is greater than that of cancer, cardiovascular disease, and diabetes combined, and is growing at a faster rate than any other ailments in the United States or Europe. Despite a considerable need for the development of treatments for central nervous system disorders, pharmaceutical companies continue to reduce investment in this area of research. Of particular concern is th Read More

Expressing functional nicotinic acetylcholine receptors (nAChRs) may be beneficial to central neurons and neuronal networks because activation of nAChRs enhances neuronal resistance to injury, improves attention, cognitive performance, and produces robust anti-inflammatory and analgesic effects in mammals. Although exogenous orthosteric nAChR ligands present valuable tools in treatment of age- and trauma-related neu Read More

Alterations in gait and balance are manifest in numerous neurological disorders such as the ataxias and Parkinson's disease, and may occur as a consequence of stroke, traumatic brain injury and chemical insults to the brain. Although the underlying etiology of these disorders differs, disturbances in gait and balance appear to reflect deficits in cholinergic pathways within the brain. During the past 40 years, both clinica Read More

The cholinergic activity in the brain is fundamental for cognitive functions. The modulatory activity of the neurotransmitter acetylcholine (ACh) is mediated by activating a variety of nicotinic acetylcholine receptors (nAChR) and muscarinic acetylcholine receptors (mAChR). Accumulating evidence indicates that both nAChR and mAChRs can modulate the release of several other neurotransmitters, modify the threshold of l Read More

Nicotinic acetylcholine receptors (nAChRs) have been pursued for decades as potential molecular targets to treat cognitive dysfunction in Alzheimer’s disease (AD) due to their positioning within regions of the brain critical in learning and memory, such as the prefrontal cortex and hippocampus, and their demonstrated role in processes underlying cognition such as synaptic facilitation, and theta and gamma wave a Read More

Background: Alzheimer disease (AD) is a neurodegenerative disorder occurring in elderly people and leading to the loss of memory, practical and speaking habits. In spite of extensive efforts undertaken during the last decades, there is still no generally recognized explanation of the origin and primary pathological changes leading to AD development. Consequently, the suggested pharmacological approaches to treat the AD pat Read More

Background: Alzheimer’s disease (AD) is the most frequent progressive neurodegenerative disease. Cholinergic dysfunction is one of the major pathological alteration, although depletion of cholinergic neurons is caused by the well-established toxicity of the beta-amyloid plaques and neurofibrillary tangles. Cholinergic dysfunctions are consequences of the decrease in acetylcholine synthesis and release, and altered fu Read More

Nicotinic acetylcholine receptors are ligand-gated transmembrane ion channels that are present at the neuromuscular junction and in different locations in the nervous system. The different subtypes of neuronal nicotinic acetylcholine receptors that are found in the brain are thought to be involved in many neurological processes such as pain, cognitive function and depression, as well as in the pathophysiology of numerous Read More

Background: Alzheimer’s disease is a neurodegenerative disease showing alterations in classical neurotransmitters, above all in the hippocampus and prefrontal/temporal cortices. In this disease, acetylcholine shows hypoactivity, noradrenaline first shows hyperactivity, and during the course of the disease an increasing hypoactivity, glutamate shows hyperactivity and excitotoxicity and GABA shows hypoactivity. In post-mortem s Read More

Development of novel pharmacotherapies for the treatment of traumatic injury to the nervous system has been ongoing for over 40 years. Despite many promising compounds discovered using animal models, no treatments have successfully translated into the clinic. The central dogma in this field is that brain trauma initiates a complex chain of biochemical events leading to secondary brain damage and sustained neurological Read More

Existing treatments of traumatic brain injury (TBI) have failed to reverse tremendous losses in productivity, independence and overall quality of life among TBI victims and therefore, cannot be viewed as sufficient. Although there is no shortage of promising basic concepts that may translate to efficacious therapies after TBI, the accumulated knowledge has yet to deliver treatments that adequately meet clinical and social dema Read More

Currently availably antipsychotic drugs are effective in ameliorating the positive symptoms of schizophrenia. Nevertheless, the cognitive impairments and negative symptoms experienced by schizophrenia patients still await effective treatment. In particular, potential cognitive enhancers have received considerable attention in the field of schizophrenia research. From among the multiple therapeutic approache Read More

Many of the most debilitating symptoms for psychiatric disorders such as schizophrenia remain poorly treated. As such, the development of novel treatments is urgently needed. Unfortunately, the costs associated with high failure rates for investigational compounds as they enter clinical trials has led to pharmaceutical companies downsizing or eliminating research programs needed to develop these drugs. One way of increasi Read More

Background: Cognitive deficits are amongst the most socially debilitating and least effectively treated symptoms of schizophrenia. The cholinergic system is a promising target for the design of novel drugs that can more effectively treat these symptoms. Methods: We review the literature supporting the dysfunction of the cholinergic system in schizophrenia, discuss the preclinical and clinical data showing that modulating t Read More

Homomeric α7 nicotinic acetylcholine receptors (nAChRs) are implicated in the regulation of cognitive processes such as memory and attention and have potential as therapeutic targets for the treatment of the cognitive deficits associated with schizophrenia. Though numerous α7 nAChR agonists have been developed, and several have progressed to clinical trials, these are derived from few common chemotypes. Conseq Read More

Lung cancers express an autocrine cholinergic loop in which secreted acetylcholine can stimulate tumor growth through both nicotinic and muscarinic receptors. Because activation of mAChR and nAChR stimulates growth; tumor growth can be stimulated by both locally synthesized acetylcholine as well as acetylcholine from distal sources and from nicotine in the high percentage of lung cancer patients who are smo Read More

Lung cancer is the leading cause of cancer-related deaths worldwide. Smoking accounts for approximately 70% of the cases of non– small cell lung cancer (NSCLC) and 90% of the cases of small-cell lung cancer (SCLC), although some patients develop lung cancer without a history of smoking. Nicotine is the most active addictive component of tobacco smoke. It does not initiate tumorigenesis in humans and rodents, but it alters Read More

Background: It is actually known that acetylcholine works as a signaling molecule in non-neuronal cells and tissues, in addition to its neuronal function as neurotransmitter. It can act on two types of receptors nicotinic and muscarinic receptors (mAChRs). The latter belong to the G protein coupled receptor family and there are five subtypes genetically cloned. Their activation triggers classical and non-classical intracellular s Read More

Background: Glaucoma is characterized as a neuropathic disease that causes progressive degeneration of retinal ganglion cells (RGCs) in the retina, resulting in irreversible loss of vision. All conventional treatments for glaucoma are focused on reducing intraocular pressure (IOP) in the anterior chamber of the eye. However, these treatments alone are insufficient to halt the progression of the disease. As a result, neurop Read More