L-amino acid oxidase is utilized to reduce the plasma level of large neutral amino acids to allow the opportunity of increased large neutral amino acid drug transport across the blood brain barrier. Preferably anti L-amino acid oxidase antibody is administered intermediate to the L-amino acid oxidase and large neutral amino acid drug administrations to deplete L-amino acid oxidase activity once the L-amino acid oxidase has caused the large neutral amino acid drug transport improving level plasma reduction of large neutral amino acids thereby to reduce or eliminate degrading of large neutral amino acid drugs by L-amino acid oxidase. The large neutral amino acid drugs include levodopa, melphalan, L-DON, azaserine, acivicin, L-alanosine and 3-(phosphonomethyl)phenylalanines. For treatment of brain tumors, the drug administration is preferably preceded by the administration of a large neutral amino acid glutathione depleting agent, e.g., L-buthionine-SR-sulfoximine. L-Amino acid oxidase is also utilized to enhance the transport of large neutral amino acid glutathione depleting agent across the blood brain barrier as an adjunct to radiation therapy of brain tumors.

Cornell Research Foundation, Inc.

Duke University

Enhancing delivery of large neutral amino acid drugs

A compound having the following structure: ##STR00001## or a pharmaceutically acceptable salt or derivative thereof. The compound may be used in the treatment or prevention of a disorder selected from appetite regulation, obesity, metabolic disorders, cachexia, anorexia, pain, inflammation, neurotoxicity, neurotrauma, stroke, multiple sclerosis, spinal cord injury, Parkinson's disease, levodopa-induced dyskinesia, Huntington's disease, Gilles de la Tourette's syndrome, tardive dyskinesia, dystonia, amyotrophic lateral sclerosis, Alzheimer's disease, epilepsy, schizophrenia, anxiety, depression, insomnia, nausea, emesis, alcohol disorders, drug addictions such as opiates, nicotine, cocaine, alcohol and psychostimulants, hypertension, circulatory shock, myocardial reperfusion injury, atherosclerosis, asthma, glaucoma, retinopathy, cancer, inflammatory bowel disease, acute and chronic liver disease such as hepatitis and liver cirrhosis, arthritis and osteoporosis.

dopa/vēzis

Enhancing delivery of large neutral amino acid drugs

Urea compounds and their use as enzyme inhibitors

Urea compounds and their use as enzyme inhibitors

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