Current Pharmaceutical Design - Volume 12, Issue 28, 2006

The production of new molecular entities endowed with salutary medicinal properties is a formidable challenge that involve several steps and requests rational target identification, recognition and avoidance of adverse properties of therapeutics before commitment to clinical trials, monitoring of clinical efficacy using surrogate markers and individualized approaches to disease treatment. The first to face up to is the i Read More

Muscarinic acetylcholine receptors mediate diverse physiological functions. At present, five receptor subtypes (M1 - M5) have been identified. The odd-numbered receptors (M1, M3, and M5) are preferentially coupled to Gq/11 and activate phospholipase C, which initiates the phosphatidylinositol trisphosphate cascade leading to intracellular Ca2+ mobilization and activation of protein kinase C. On the other ha Read More

L-glutamate is considered the main excitatory neurotransmitter in the mammalian brain. Paradoxically, Lglutamate is also the most important excitotoxin pivotally involved in the aetiology of several neurodegenerative diseases such as stroke, Alzheimer, Parkinson, amyotropic lateral sclerosis, Huntington and neuropathic pain. L-glutamate signalling is transduced both presynaptically and postsynaptically by metabotro Read More

Cyclic nucleotide-gated (CNG) ion channels play a central role in vision and olfaction, generating the electrical responses to light in photoreceptors and to odorants in olfactory receptors. These channels have been detected in many other tissues where their functions are largely unclear. The use of gene knockouts and other methods have yielded some information, but there is a pressing need for potent and specific pharmacologi Read More

The 5-HT3 receptor is a member of the Cys-loop family of ligand-gated ion channels. These receptors are located in both the peripheral and central nervous systems, where functional receptors are constructed from five subunits. These subunits may be the same (homopentameric 5-HT3A receptors) or different (heteropentameric receptors, usually comprising of 5-HT3A and 5-HT3B receptor subunits), with the latter having Read More

Potassium channels form highly K+ ion-selective pores in the plasma membrane of excitable cells. Voltagegated potassium (Kv) channels open in response to membrane depolarization to allow rapid diffusion of K+ ions out of the cell, thus repolarizing the cell to restore a negative resting membrane potential. Inherited mutations in Kv channel genes produce abnormal cellular repolarization and cause diseases of excitable Read More

Mechanosensitivity is a property common to many cell types. Because channels gated by mechanical stimuli (mechanosensitive channels, MSCs) are implicated in many normal and pathological cellular responses, they present a valid target for therapeutic agents. However the process of mechanotranduction, the structure, function and pharmacology of eukaryotic MSCs are not well understood and matching experimental Read More

The use of general anaesthetics has facilitated great advantages in surgery within the last 150 years. General anaesthesia is composed of several components including analgesia, amnesia, hypnosis and immobility. To achieve these components, general anaesthetics have to act via multiple molecular targets at different anatomical sites in the central nervous system. Much of our current understanding of how anaesthetics w Read More

Early detection and treatment of cancers have increased survival and improved clinical outcome. The development of metastases is often associated with a poor prognostic of survival. Finding early markers of metastasis and developing new therapies against their development is a great challenge. Since a few years, there is more evidence that ionic channels are involved in the oncogenic process. Among these, volt Read More