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70 results about "D aspartate" patented technology

Topical compositions comprising opioid analgesic and NMDA antagonist

A topical opioid paradigm was developed to determine analgesic peripheral effects of morphine. Topical morphine as well as peptides such as [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO) produced a potent, dose-dependent analgesia using the radiant heat tailflick assay. The topical drugs potentiated systemic agents, similar to the previously established synergy between peripheral and central sites of action. Local tolerance was rapidly produced by repeated daily topical exposure to morphine. Topical morphine tolerance was effectively blocked by the N-Methyl-D-Aspartate (NMDA) receptors antagonist MK801 and ketamine given either systemically or topically. NMDA receptor antagonists reversed pre-existing morphine tolerance. The activity of topical NMDA antagonists to block local morphine tolerance suggests that peripheral NMDA receptors mediate topical morphine tolerance. Morphine was cross tolerant to [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO), but not to morphine-6 beta -glucuronide, implying different mechanisms of action. These observations have great importance in the design and use of opioids clinically. Topical pharmaceutical compositions comprising an analgesic that functions through an opiate receptor and an NMDA receptor antagonist for producing analgesia without inducing tolerance are described.
Owner:MEMORIAL SLOAN KETTERING CANCER CENT

HPLC-MS/MS (High Performance Liquid Chromatography-Mass Spectrum/Mass Spectrum) technique-based method for detecting blood concentration of NMDA (N Methyl D Aspartate) receptor antagonist JCC-02

The invention provides an HPLC-MS/MS (High Performance Liquid Chromatography-Mass Spectrum/Mass Spectrum) technique-based method for detecting blood concentration of a NMDA (N Methyl D Aspartate) receptor antagonist JCC-02 and relates to the field of drug analysis. The method comprises the following steps of: sequentially adding methanol, acetonitrile and an internal standard working solution intoplasma of an SD (Sprague Dawley) rat after intragastric administration of the JCC-02, eddying and dissolving supernatant by using a mobile phase to obtain a preprocessed sample, wherein the internalstandard working solution was a gliclazide methanol solution; and carrying out gradient elution by taking acetonitrile-formic acid water mixed solution as a mobile phase and by adopting HPLC-MS/MS technique, carrying out chromatographic separation by using a Venusil ASB C8 chromatographic column, detecting through a second-stage mass spectrometry and carrying out quantitative analysis. The methodhas the advantages of being strong in specificity, high in sensitivity, small in sample sampling amount, simple and rapid in preprocessing and short in analysis period; and proved by methodology, themethod is accurate and reliable and is suitable for drug concentration determination of the JCC-02 in the plasma of the SD rat and pharmacokinetic study.
Owner:THE FIRST HOSPITAL OF CHINA MEDICIAL UNIV

Polyamine conjugates as selective NMDA inhibitors and anti-cancer drugs

Polyamine compounds, method of synthesis and method of use for anti-cancer purposes, for enhancing the activity of existing anti-cancer drugs, as well as, for inhibiting N-Methyl-D-Aspartate (NMDA) receptors found in neurotransmission systems are provided. Certain polyamine motifs have been identified that can be attached to toxic agents to facilitate their access to cancer cells as well as polyamine compounds of surprising cytotoxicity with selectivity in killing cancer cells, and surprising utility in the treatment of Alzheimer's disease and brain stroke. It includes an illustrative conjugate system with examples of a triamine or a tetraamine appended to a cytotoxic agent. Included is a general strategy to enhance cell uptake by attaching a polyamine vectoring system with an example of a triamine vector attached to an existing anti-cancer drug to improve its chemotherapeutic potency. There is an illustration of tetraamine derivatives which have surprising enhanced selectivity in inhibiting N-methyl-D-aspartate (NMDA) receptors involved in neurotransmission. Several ligands can affect the activity of this receptor, which has been shown to initiate cell death under stroke conditions (lack of oxygen). Tetraamine derivatives which bind or inhibit the action of the NMDA receptor provide new therapy for NMDA-associated human diseases, such as Alzheimer's disease and stroke.
Owner:UNIV OF CENT FLORIDA RES FOUND INC
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