G.d. Searle & Company

C. D. Searle & Co.

Alex A Cordi

Gail E Handelmann

Brian K Cheng

Nancy M Gray

Michael S Dappen

Hugo J Gorissen

Michel R Jans

William F Hood

Michael L Vazquez

Robert M Williams

Philippe Janssens De Varebeke

A class of Glycine B partial agonists is described for use in memory and learning enhancement or for treatment of a cognitive disorder. Preferred Glycine B partial agonists include the compound D-cycloserine and its prodrug compounds.

Use of a glycine B partial agonist for memory and learning enhancement

A composition is described for use in memory and learning enhancement or for treatment of a cognitive disorder or a psychotic disorder. This composition contains the compound D-cycloserine and D-alanine and provides reduced adverse side effects typically associated with chronic D-cycloserine use.

Composition containing D-cycloserine and D-alanine for memory and

Compositions containing certain indole-2-carboxylate compounds and derivatives are described as being therapeutically effective in treatment of CNS disorders resulting from neurotoxic damage or neurodegenerative diseases, particularly those CNS disorders resulting from ischemic events. Preferred compounds are of the formula ##STR1## wherein each of R.sup.5 and R.sup.6 is independently selected from hydrido, bromo, chloro and fluoro, and wherein each of R.sup.10 and R.sup.12 is independently selected from hydrido and lower alkyl, and pharmaceutically-acceptable salts thereof.

Compositions containing indole-2-carboxylate compounds for treatment of

A class of vinyl glycine derivatives is described for use in memory and learning enhancement or for treatment of a cognitive disorder. The vinyl glycine derivatives of particular interest are compounds of Formula I wherein the double bond is in trans configuration, R.sup.1 is lower alkyl, R.sup.2 is hydrido, R.sup.3 is amino and X is hydroxymethyl. ##STR1##

Vinyl Glycine derivatives for memory and learning enhancement or

A class of Glycine B partial agonists is described for use for treatment of psychosis. Preferred Glycine B partial agonists include amino-isoxazolidone compounds such as D-cycloserine and its prodrugs.

Use of a Glycine B partial agonist as an antipsychotic

Deuterated 2-alkylaminoacetamide compounds are described having the alpha carbon of the alkyl side chain of the compounds substituted by one or two deuterium atoms. These compounds have pharmacokinetic properties which enable treatment of CNS diseases with lower toxic effects. These compounds are also useful in evaluating the metabolic fate of non-deuterated counterpart compounds. Of particular interest are compounds of Formula I: ##STR1## wherein X is deutero or hydrido; wherein R.sup.1 is selected from alkyl and aralkenyl; wherein each of R.sup.2 and R.sup.3 is independently selected from hydrido and alkyl; wherein each of R.sup.1, R.sup.2 and R.sup.3 having a substitutable position may be substituted with one or more halo radicals; or a pharmaceutically-acceptable salt thereof.

Alpha-deuterated 2-alkylaminoacetamide derivatives having reduced

A class of phenyl glycine compounds is described for treatment to reduce neurotoxic injury associated with anoxia or ischemia which typically follows stroke, cardiac arrest or perinatal asphyxia. The treatment includes administration of a phenyl glycine compound alone or in a composition in an amount effective as an antagonist to inhibit excitotoxic actions at major neuronal excitatory amino acid receptor sites.

Phenyl glycines for use in reducing neurotoxic injury

The compound D-4-amino-3-isoxazolidone, its pharmaceutically-acceptable salts and its prodrug compounds are described as having cognitive-enhancing activity.

D-cycloserine and its prodrugs as cognitive enhancers

Certain 4(5)-(biarylethyl)imidazole derivatives are selectiv3 .alpha..sub.2 -adrenergic receptor blockers and are useful as anti-depressant agents.

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St. Louis, MO, United States of America

Alex A Cordi