Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1989-07-27
1992-02-11
Chaudhuri, Olik
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514432, 514423, A01N 4380
Patent
active
050876333
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention is in the field of clinical neurology and relates specifically to compounds, formulations and methods for memory enhancement and for treatment of cognitive disorders.
BACKGROUND OF THE INVENTION
There are many memory-related conditions for which therapeutic treatments are under investigation, such as methods to enhance memory or to treat memory dysfunction. For example, memory dysfunction is linked to the aging process, as well as to neurodegenerative diseases such as Alzheimer's disease. Also, memory impairment can follow head trauma or multi-infarct dementia. Many compounds and treatments have been investigated which can enhance cognitive processes, that is, which can improve memory and retention.
The compound piracetam has been prescribed for treatment to enhance memory [Giurgea et al, Arch. Int. Pharmacodyn. Ther., 166, 238 (1967)]. U.S. Pat. No. 4,639,468 to Roncucci et al describes the compound milacemide which is mentioned as useful for treatment of memory troubles. Further investigations of milacemide have documented the memory-enhancing capabilities of milacemide in human subjects [B. Saletu et al, Arch. Gerontol. Geriatr., 5, 165-181 (1986)].
Other compounds having effects on the Central Nervous System (CNS) have been investigated. For example, the compound D-cycloserine, in its D-and L-isomer forms, has been evaluated for effects on the upper region of the CNS [O. Mayer et al, Arzneim. Forsch., 21(2), 298-303 (1971)]. These cycloserine isomers have also been evaluated for psychological and physiological effects in healthy human subjects [M. Vojtechovsky, Act. Nerv. Super., 7(3), 269 (1965); V. Vitek et al, Psychopharmacologia, 7(3), 203-219 (1965)].
BRIEF DESCRIPTION OF FIGURES
FIG. 1 is a graph showing concentration of D-cycloserine influence on maximal glycine stimulation of TCP binding in the presence of various concentrations of glycine.
FIG. 2 is a graph showing concentration of glycine influence on maximal glycine stimulation of TCP binding in the presence of various concentrations of D-cycloserine.
DESCRIPTION OF THE INVENTION
Improvement of cognitive function or treatment of a cognitive dysfunction is achieved by treatment of an animal with a therapeutically-effective amount of a Glycine B partial agonist or a prodrug thereof. Such Glycine B partial agonist may be provided by one or more compounds selected from the family of compounds of Formula I: ##STR1## wherein R.sup.1 is selected from hydrido, alkyl, haloalkyl, alkoxyalkyl, cycloalkyl, aralkyl and aryl; wherein R.sup.2 is selected from hydrido, alkyl, aralkyl, aryl, ##STR2## wherein R.sup.1 and R.sup.2 may be taken together to form a Schiff-base derived group selected from derivatives of aldehydes and ketones; wherein R.sup.3 is selected from hydrido, alkyl, haloalkyl, alkoxy, alkoxyalkyl, cycloalkyl, aralkyl and aryl; or a pharmaceutically-acceptable salt thereof. The phrase "improvement of cognitive function" embraces treatment to improve or enhance memory and treatment to address a cognitive deficit linked to a neurological disorder.
A preferred family of compounds consists of compounds wherein R.sup.1 is selected from hydrido, lower alkyl, haloalkyl, cycloalkyl, alkoxyalkyl, phenalkyl and phenyl; wherein R.sup.2 is selected from hydrido, lower alkyl, phenalkyl, phenyl, ##STR3## wherein the Schiff-base derived group is derived from acetylacetone, salicylaldehyde, benzophenone derivatives and acetylacetic acid esters; and wherein R.sup.3 is selected from hydrido, lower alkyl and benzyl.
A more preferred group of compounds within Formula I consists of these compounds wherein R.sup.1 is hydrido; wherein R.sup.2 is selected from ##STR4## wherein the Schiff-base derived group is selected from ##STR5## wherein each of X and Y is independently one or more groups selected from hydrido, lower alkyl and halo; and wherein R.sup.3 is selected from hydrido, lower alkyl and phenyl.
A most preferred group of compounds within Formula I consists of those compounds wherein R.sup.1 is selected from hy
REFERENCES:
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Cordi Alex A.
Handelmann Gail E.
Monahan Joseph B.
Chaudhuri Olik
G. D. Searle & Co.
Griffis Andrew
Keane J. Timothy
Matukaitis Paul D.
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