Selective cytokine inhibitory drugs for treating disorders of the central nervous system

Abstract

Methods of treating, preventing and / or managing central nervous system disorders, such as Parkinson disease, Alzheimer disease, mild cognitive impairment, Huntington disease, Amytophic Lateral Sclerosis, depression and defective long-term memory, and related syndromes are disclosed. Specific methods encompass the administration of a selective cytokine inhibitory drug, or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, clathrate, or prodrug thereof, alone or in combination with a second active ingredient. Pharmaceutical compositions, single unit dosage forms, and kits suitable for use in methods of the invention are also disclosed.

Description

1. Field of invention [0001] The present invention relates in part to methods of treating, preventing and / or managing disorders of the central nervous system including, but not limited to, Parkinson's disease, Alzheimer's disease, mild cognitive impairment, Huntington's disease, muscular atrophy Lateral sclerosis, depression and long-term memory loss and related diseases, the method comprising administering selective cytokine inhibitory drugs or pharmaceutically acceptable salts, solvates, hydrates, stereoisomers, clathrates thereof or prodrugs. 2. Background of the invention [0002] CNS disorders affect a wide range of populations to varying degrees. In general, a major feature of such disorders includes marked cognitive or memory impairment, which represents a marked regression of previous levels of functioning. Dementia, for example, characterized by several cognitive impairments including marked memory deficits and which may be present alone or as a predominant featur...

AI Technical Summary

Problems solved by technology

Zhu et al., CNS Drug Reviews, Vol.7, No.4, 387-398, 2001. It is reported that PDE4 is mainly used for the hydrolysis of cyclic nucleotides cAMP and cGMP, especially in nerve and immune cells. Same as above. Ripram causes an increase in intracellular cAMP and increases the synthesis and release of norepinephrine, which enhances central noradrenergic transmission. Ibid. Rolipram attenuates endogenous depression and Inflammation. Ibid. However, there are some discrepancies between the in vitro and in vivo effects of rolipram, and between the results obtained in animal models and clinical studies. Ibid. Also, due to its behavior and other side effects Clinical use is limited. Therefore, selective PDE4 inhibitors with higher potency and lower toxicity are urgently needed.

[0024] 2.5 long term memory deficit

These compounds potently inhibit TNF-α production, but show only modest inhibition of LPS-induced IL1β and IL12, and do not inhibit IL6 even at high drug concentrations

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