Current Medicinal Chemistry - Central Nervous System Agents - Volume 5, Issue 2, 2005

Monoamine transporters (MAT) are the target molecules of cocaine for induction of its central stimulating effect, resultant reward. Sensitization of central nervous system stimulation by cocaine is produced by intermittent use of cocaine and typically appears in behavioral hyperactivity in animals. Na+ channels are other important molecules for induction of seizures of cocaine in abuse. The mechanisms for the expression Read More

The pharmacological treatment of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS) currently represents a major medical challenge. The mechanisms involved in the apoptotic neuronal cell death, associated with such disorders, are still not clear, but recent data suggest that cyclindependent kinases (CDKs) play a prominent role (Liu et al., 2003). Canoni Read More

Alzheimer's disease (AD) is the most common form of neurodegenerative disease with dementia in the elderly. Besides the pathological hallmarks of the disease, which include cerebral deposits of amyloid-β (Aβ) peptides and neurofibrillary tangles, AD brain exhibits clear evidence of a chronic inflammatory process. Epidemiological studies have shown that long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduces Read More

At least nine neurodegenerative diseases are caused by the expansion of a polyglutamine (polyQ) tract in the associated disease proteins. Although these proteins are normally expressed in either the cytoplasm or the nucleus, polyQ expansion can cause them to accumulate and aggregate in the nucleus. Moreover, addition of an expanded polyQ tract to a small cytoplasmic protein, hypoxanthine-guanine-phosphoribosyltransferas Read More

Injury to the peripheral nerve can lead to paradoxical changes in functioning such that there is an ongoing dysesthesia and an altered processing such that low threshold stimuli are responded to in humans and animals as if they were painful. What are the mechanisms underlying these anomalous behaviors? The biological changes induced by nerve injury are complex. To attribute functional relevance to the many chang Read More

The ventral medullary surface of the medulla oblongata is known as the site of the central chemosensitive neurons in humans. These neurons sense decrease in pH of the cerebrospinal fluid followed by hypercapnia (increased arterial CO2) and induce hyperventilation. Recently, several advances have been made in understanding central chemosensitivity at the molecular and cellular levels. Recent studies have identified Read More

Activated innate immune response in brain has been extensively associated with several diseases, including Alzheimer's disease, HIV-associated dementia, ischemia, head trauma, stroke, cerebral palsy, axonal degeneration in multiple sclerosis, and autism. Although initially investigated because of its role innate immune response to microorganisms, the CD14/Toll-like receptor pathway is now appreciated as a critical ele Read More

It is well established that the neuroactive steroids can modulate neuronal activity in the peripheral and central nervous system causing a variety of behavioral and neuroendocrine changes in humans and animals. It is largely believed that their effects on neurosensory processing and neuronal excitability are primarily mediated by effects on various ligandgated ion channels, with much attention focused on the modulation of γ-a Read More