By being an antagonist of glutamate and other receptors, kynurenic acid serves as endogenous neuroprotectant in several pathologies the brain. Unfortunately, systemic administration is hindered by its low permeability through blood–brain barrier. One possibility to overcome this problem use analogues with similar biological activity acid, but increased We synthesized six novel aminoalkylated am...

Ethanol affects cognition in a number of ways. Indirect effects include intoxication, withdrawal, brain trauma, central nervous system infection, hypoglycemia, hepatic failure, and Marchiafava-Bignami disease. Nutritional deficiency can cause pellagra and Wernicke-Korsakoff disorder. Additionally, ethanol is a direct neurotoxin and in sufficient dosage can cause lasting dementia. However, ethan...

In the past decade there has been a resurgence of interest in the clinical use of inert gases. In the present paper we review the use of inert gases as anesthetics and neuroprotectants, with particular attention to the clinical use of xenon. We discuss recent advances in understanding the molecular pharmacology of xenon and we highlight specific pharmacological targets that may mediate its acti...

The fundamental premise of neuroprotection has historically focused on the prevention of neuronal death. However, despite tremendous advances in the molecular biology of intraneuronal mechanisms and pathways, a clinically effective neuroprotectant does not yet exist. This problem is especially clear for stroke, for which a large number of neuroprotection trials have failed. The concept of the n...

Nitric oxide (nitrogen monoxide; NO) is a simple molecule with diverse biological functions. NO and related reactive nitrogen oxide species (RNOS) mediate intricate physiological and pathophysiological effects in the central nervous system. Depending on environmental conditions, NO and RNOS can initiate and mediate neuroprotection or neurotoxicity either exclusively or synergistically with othe...

Excitotoxicity has been implicated in the etiology of ischemic stroke, chronic neurodegenerative disorders, and very recently, in glioma growth. Thus, the development of novel neuroprotectant molecules that reduce excitotoxic brain damage is vigorously pursued. We have used an ionic current block-based cellular assay to screen a synthetic combinatorial library of trimers of N-alkylglycines on t...

BACKGROUND Xenon, the "inert" gaseous anesthetic, is an antagonist at the N-methyl-D-aspartate (NMDA)-type glutamate receptor. Because of the pivotal role that NMDA receptors play in neuronal injury, the authors investigated the efficacy of xenon as a neuroprotectant in both in vitro and in vivo paradigms. METHODS In a mouse neuronal-glial cell coculture, injury was provoked either by NMDA, g...