The Dupont Merck Pharmaceutical Company

Richard A Earl

Wendell W Wilkerson

Melvyn J Myers

Victor J Nickolson

Christopher A Teleha

Matthew Ernst Voss

Philip Ma

Paul E Aldrich

Paul R Hartig

Robert Zaczek

Victor J De Noble

Victor J DeNoble

Simon Piers Aiken

Kimi F De Noble

Barry Stephen Brown

Compounds of Formula (I) have been shown to enhance the release of the neurotransmitter acetylcholine, and thus may be useful in the treatment of diseases of man where subnormal levels of this neurochemical are found, such as in Alzheimer's disease, and other conditions involving learning and cognition. This invention describes compounds, pharmaceutical compositions and methods of treatment comprising compounds of Formula (I): ##STR1##

Polycyclic systems, and derivatives thereof, as neurotransmitter release

Compounds which block neuronal M-channels are useful for treating conditions involving neurotransmitter deficiencies, traumatic brain injury, or the depressive phase of bipolar disorder. Compounds can be evaluated for utility in treating these conditions by determining whether they are capable of blocking neuronal M-channels.

Blockade of neuronal m-channels as a therapeutic approach to the

There are provided novel 1,4-dihydropyridine compounds, compositions containing them and methods of using them to treat congestive heart failure.

4-Heteroaryl- 1,4-dihydropyridine compounds with calcium agonist and

Compounds of Formula I have been shown to enhance the release of the neurotransmitter acetylcholine and thus may be useful in the treatment of diseases learning and cognition. The compounds of this invention are ##STR1## where Q is ##STR2## A and B are independently selected from H, R.sup.4, --OH and --OCOR.sup.4, or

Neurotransmitter releasers useful for cognition enhancement

Cognitive defeciencies or neurological dysfunction in mammals are treated with .alpha.,.alpha.-disubstituted aromatic or heteroaromatic compounds. The compounds have the formula: ##STR1## or a salt thereof wherein X and Y are taken together to form a saturated or unsaturated carbocyclic or heterocyclic first ring and the shown carbon in said ring is .alpha. to at least one additional aromatic ring or heteroaromatic ring fused to the first ring;

.alpha.,.alpha.-disubstituted aromatics and heteroaromatics as cognition

4-heteroaryl- and 4-aryl-1,4-dihydropyridine compounds

Compounds of the following formula have been shown to enhance the release of the neurotransmitter acetylcholine, and thus may be useful in the treatment of diseases of man involving learning and cognition, where subnormal levels of this neurochemical are found ##STR1## wherein R.sup.1 is 4-,3-, or 2-pyridyl, 2-fluoro-4-pyridyl or 3-fluoro-4-pyridyl;

There are provided novel 1,4-dihydropyridine compounds possessing both calcium agonist and alpha.sub.1 -antagonist activity useful for treating congestive heart failure, pharmaceutical compositions containing them and methods of using these compounds to treat congestive heart failure in a mammal.

2-amino-1, 4-dihydropyridine derivatives with calcium agonist and

.alpha., .alpha.-disubstituted aromatics and heteroaromatics as

This disclosure relates to a method of treating a neurological dysfunction in a mammal using a combination of at least one neurotransmitter enhancer and at least one serotonin receptor antagonist.

Method of treating neurological dysfunction using neutrotransmitter

2-amino-1,4-dihydropyridine derivatives with calcium agonist and

4-heteroaryl-and 4-aryl-1,4-dihydropyridine, derivatives with calcium

A fluorene compound, 4,4'-[9H-fluoren-9-ylidenebis(methylene)]bispyrimidine, or a pharmaceutically acceptable salt thereof is useful in treating various neurological disorders in mammals. This compound has efficacy over a broad dosage range as measured by hypoxia induced cognition impairment and has a wide safety margin as measured by the ratio of cognition to the onset of overt symptoms.

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Wilmington, DE, United States of America

Richard A Earl