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

[0021] The present invention thus relates to methods of treating Attention Deficit Disorder and Attention Deficit Hyperactivity Disorder in children and adults while providing for reduced side effects, reduced euphoric effect and reduced potential for abuse potential through administration of d-threo-methylphenidate (2R:2′R) of the formula: or a pharmaceutically acceptable salt thereof, substantially free of the l-threo isomer.

[0022] The invention further relates to methods of treating AIDS-related dementia and related cognitive disorders while providing for reduced side effects, reduced euphoric effect, and reduced abuse potential through administration of d-threo-methylphenidate (2R:2′R) of the formula: or a pharmaceutically acceptable salt thereof, substantially free of the l-threo isomer.

[0023] Prescription of methylphenidate to treat AIDS cognitive decline and AIDS Dementia Complex associated with HIV infection is becoming increasingly popular. However, high doses in excess of 40 mg / day are not well tolerated by a substantial number of HIV-infected patients when treated over weeks or months. Brown, G., Int'l J. Psychiatry. Med., 25:21-37 (1995). The d-threo isomer use of the present invention thus enables a lowered dosing therapy resulting in improved efficacy for diseased patients and particularly HIV-infected patients.

[0024] Moreover, administration of the d-threo isomer to patients will result in decreased side effects, reduced euphoric effect, and substantially reduce the potential for abuse of the product.

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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