Pharmaceutical Compositions and Methods Utilizing a D-Amino Acid

Abstract

The present invention provides a pharmaceutical composition for oral administration comprising a D-amino acid combined with an antioxidant selected from the group consisting of vitamin E, vitamin C, a glutathione or a precursor thereof.

Description

[0001]The present invention relates to a pharmaceutical composition for treating a neuropsychiatric disorder and to methods utilizing the same.BACKGROUND OF THE INVENTION[0002]D-serine is a naturally occurring amino acid and one of a class of amino acids that is known to be useful for treatment of neuropsychiatric disorder but which may cause nephrotoxicity when administered to rodents. In the brain, D-serine serves as a modulator of N-methyl-D-aspartate (NMDA)-type glutamate receptors. Deficiencies of D-serine or of NMDA neurotransmission may contribute to the pathophysiology of multiple neuropsychiatric disorders including schizophrenia, Alzheimers disease, attention deficit hyperactivity disorder, autism, depression, and movement disorders (Javitt 2000; Tsai 2001). It has been proposed therefore that oral administration of D-serine at doses of 1 mg-100 g may serve as a novel treatment for these disorders. Clinical use of D-serine and of similar D-amino acids is potentially limite...

AI Technical Summary

Benefits of technology

[0008]Thus, the present invention derives from the discovery that orally administered precursors of glutathione (GSH), including the compounds N-acetylcysteine and L-cysteine, prevent nephrotoxicity induced by the amino acid D-serine. The present invention provides a method for oral administration of D-serine or similar amino acids that minimizes risks of nephrotoxicity. This formulation therefore represents a significant, clinically useful improvement over use of D-serine or other amino acids alone as medicaments for neuropsychiatric or other medical conditions.

Problems solved by technology

Use of these compounds in clinical settings, however, is potentially limited by nephrotoxicity.

However, non-oral routes of administration are not feasible for clinical treatment, necessitating alternative approaches.

However, oral NAC or other glutathione precursors have not been found to be effective treatments for nephrotoxicity induced by a wide variety of agents including contrast agents and chemotherapies.

Despite intensive investigation of treatments that might reverse D-serine nephrotoxicity, oral NAC or other glutathione precursors have not been evaluated previously against D-serine-induced nephrotoxicity either in humans or animal models.