introduction: neuropathic pain syndromes are changes resulting from damage to neuronal pathways that are characterized by spontaneous burning sensation with accompanying allodynia and hyperalgesia. since the treatments of neuropathic pain are poorly understood and existing treatments are often ineffective, it is important to increase our understanding of the neuropathic pain states in order to ...

PURPOSE ALT-801 is a bifunctional fusion protein comprising interleukin-2 (IL-2) linked to a soluble, single-chain T-cell receptor domain that recognizes a peptide epitope (aa264-272) of the human p53 antigen displayed on cancer cells in the context of HLA-A*0201 (p53+/HLA-A*0201). We evaluated the safety, pharmacokinetics, and pharmacodynamics of ALT-801 in p53+/HLA-A*0201 patients with metast...

Antagonism of N-methyl-D-aspartate (NMDA) receptors by phencyclidine (PCP) is thought to underlie its ability to induce a schizophrenia-like syndrome in humans, yet evidence indicates it has a broader pharmacological profile. Our previous lesion studies highlighted a role for serotonergic projections from the median, but not dorsal, raphe nucleus in mediating the hyperlocomotor effects of PCP, ...

Using whole cell recording from CA1 hippocampal pyramidal neurons in slices, we examined the progressive decrease of N-methyl-D-aspartate receptor-mediated synaptic responses in the presence of the open-channel blocker MK-801. Previous studies analyzing this decrease have proposed that hippocampal synapses fall into two distinct classes of release probabilities, whereas studies based on other m...

The combination of central fluid percussion traumatic brain injury (TBI) followed 24 h later by a bilateral entorhinal cortical deafferentation (BEC) produces profound cognitive morbidity. We recently showed that MK-801 given prior to TBI in this insult improved spatial memory for up to 15 days. In the present study we examine whether MK-801 treatment of the BEC component in the combined insult...

An interaction between N-methyl-D-aspartate (NMDA) and MK-801 was examined in mice using a modified elevated plus-maze paradigm that allows assessment of the adaptive form of spatial memory. NMDA administered (s.c.) immediately after the acquisition session protected the animals against the amnesia induced by MK-801 given shortly before the retention session. Behavioral performance, expressed a...

BACKGROUND ALZ-801 is an orally available, valine-conjugated prodrug of tramiprosate. Tramiprosate, the active agent, is a small-molecule β-amyloid (Aβ) anti-oligomer and aggregation inhibitor that was evaluated extensively in preclinical and clinical investigations for the treatment of Alzheimer's disease (AD). Tramiprosate has been found to inhibit β-amyloid oligomer formation by a multi-liga...