Method of treating attention deficit disorders with D-threo methylphenidate

Abstract

Methods for treating Attention Deficit Disorder, Attention Deficit Hyperactivity Disorder, AIDS Dementia Complex and cognitive decline in HIV-AIDS while minimizing drug hypersensitivity, toxicity, side effects, euphoric effect, and drug abuse potential by administration of d-threo-methylphenidate or pharmaceutically acceptable salts thereof.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a divisional application of Ser. No. 10 / 395,444, filed Mar. 24, 2003; which is a continuation of Ser. No. 09 / 864,617, filed May 24, 2001; which is a divisional application of application Ser. No. 09 / 337,310, filed Jun. 21, 1999 (now U.S. Pat. No. 6,255,325); which is a divisional of application Ser. No. 08 / 937,684, filed Sep. 29, 1997 (now U.S. Pat. No. 5,922,736); which is a continuation-in-part of application Ser. No. 08 / 827,230, filed Apr. 2, 1997 (now U.S. Pat. No. 5,908,850) and of application Ser. No. 08 / 647,642, filed May 15, 1996 (now abandoned); the former being a continuation of Ser. No. 08 / 567,131, filed Dec. 4, 1995, (now abandoned) and the latter being a continuation-in-part of application Ser. No. 08 / 583,317, filed Jan. 5, 1996, (now U.S. Pat. No. 5,733,756. The above are incorporated herein by reference in their entirety.FIELD OF THE INVENTION [0002] The present invention relates to methods of treating...

AI Technical Summary

Benefits of technology

The present invention is based on the discovery that d-threo-methylphenidate (2R:2′R) has better therapeutic activity with reduced side effects, while l-threo-methylphenidate produces undesirable side effects, euphoria, and potential for drug abuse. The invention relates to methods of treating Attention Deficit Disorder and Attention Deficit Hyperactivity Disorder in children and adults while reducing side effects, euphoric effect, and potential for abuse through the use of d-threo-methylphenidate (2R:2′R) or a pharmaceutically acceptable salt thereof, substantially free of the l-threo isomer. The invention also relates to methods of treating AIDS-related dementia and related cognitive disorders while reducing side effects, euphoric effect, and potential for abuse through the use of d-threo-methylphenidate (2R:2′R) or a pharmaceutically acceptable salt thereof, substantially free of the l-threo isomer. The use of the d-threo isomer results in lower dosing requirements, improved efficacy, and reduced side effects, euphoric effect, and potential for abuse.

Problems solved by technology

Symptoms of ADD include distractibility and impulsivity.

Current administration of racemic methylphenidate, however, results in notable side effects such as anorexia, weight loss, insomnia, dizziness and dysphoria.

Additionally, racemic methylphenidate which is a Schedule II controlled substance, produces a euphoric effect when administered intravenously or through inhalation, and thus carries a high potential for substance abuse in patients.

As described above, racemic methylphenidate which is a Schedule II controlled substance, produces a euphoric effect when administered intravenously or through inhalation, and thus carries a high potential for drug abuse in AIDS patients.

For example, while the threo-racemate of methylphenidate produces the desired Central Nervous System action, the erythro-racemate contributes to hypertensive side effects and exhibits lethality in rats.

Although l-threo-methylphenidate is rapidly and stereo-selectively metabolized upon oral administration, intravenous administration or inhalation results in high l-threo-methylphenidate serum levels.

This study noted a 5-fold increase in plasma levels of d-threo-methylphenidate in children treated with racemic methylphenidate, but was otherwise inconclusive with regard to the efficacy of a single methylphenidate isomer at therapeutically significant doses.

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