Nelson Research & Development Company

Whitby Research, Inc.

Nelson Research & Development

Alan S Horn

James V Peck

Paul A Jerabek

Sandor Agoston

This invention provides a method for treating the symptoms of schizophrenia by interacting selectively with presynaptic dopaminergic D.sub.2 receptors without appreciably activating postsynaptic dopamine receptors which comprises administering to a schizophrenic an effective amount of a compound selected from the group consisting essentially of the stereoisomers of mixtures thereof of compounds represented by the general formula: ##STR1## wherein R.sub.1 is selected from the group consisting of pyridyl and ##STR2## X is oxygen or sulfur, Y, if present, is selected from the group consisting of hydroxy, nitro, cyano, azido, amino, acylamino, carboxyamido, trifluoromethyl, sulfate, sulfonamido halogen, hydrocarbyl and hetero atom-substituted hydrocarbyl radicals, wherein said heteroatoms are selected from the group consisting of halogen, nitrogen, oxygen, sulfur and phosphorus and said hydrocarbyl radicals comprise from 1 to 12 carbon atoms, and a is an integer between zero and 3, R.sub.2 is H, R.sub.4 is OA and R.sub.3 is selected from the group consisting of H and OA, A is H or is selected from the group consisting of hydrocarbyl radicals, or ##STR3## R.sub.5 is selected from the group consisting of hydrocarbyl radical and n is 2 or 3.

Method for treating schizophrenia

Certain novel compounds having the structural formula ##STR1## where R.sub.2, R.sub.3 and R.sub.4 are each selected from the group consisting of H and OA; A is H or is selected from the group consisting of hydrocarbyl radicals, e.g. lower alkyl radicals, i.e. methyl, ethyl, propyl, etc., or ##STR2## wherein R.sub.5 is selected from the group consisting of hydrocarbyl radicals, e.g. alkyl and aromatic residues; n is 2 or 3; and R.sub.1 is selected from the group consisting of organic radicals having fused aromatic rings, that is, radicals comprising at least two rings that share a pair of carbon atoms or share a carbon and nitrogen atom are useful for inducing a dopaminergic response and reducing the intraocular pressure in a mammal.

Substituted 2-aminotetralins and pharmaceutical use

Certain novel compounds having the structural formula ##STR1## wherein R.sub.2, R.sub.3 and R.sub.4 are each selected from the group consisting of H and OA; A is H or is selected from the group consisting of hydrocarbyl radicals, e.g. lower alkyl radicals, i.e. methyl, ethyl, propyl, etc., or ##STR2## wherein R.sub.5 is selected from the group consisting of hydrocarbyl radicals, e.g. alkyl and aromatic residues; n is 2 or 3; and R.sub.1 is selected from the group consisting of organic radicals having fused aromatic rings, that is, radicals comprising at least two rings that share a pair of carbon atoms or share a carbon and nitrogen atom are useful for inducing a dopaminergic response and reducing the intraocular pressure in a mammal.

Substituted 2-aminotetralins

This invention provides a method for treating the symptoms of parkinsonism which comprises administering to a human or other mammal suffering from the symptoms of parkinsonism an effective amount of a compound selected from the group consisting of optically-active or racemic compounds represented by the general formula: ##STR1## wherein R.sub.1 is selected from the group consisting of organic radicals methyl, substituted or unsubstituted phenyls, pyridyl, hydroxphenyl, ##STR2## X is oxygen or sulfur, Y is selected from the group consisting of hydroxy, nitro, cyano, axido, amino, acylamino, carboxyamido, trifluoromethyl, sulfate, sulfonamido, halogen, hydrocarbyl and hetero atom-substituted hydrocarbyl radicals, wherein said heteroatoms are selected from the group consisting of halogen, nitrogen, oxygen, sulfur and phosphorus and said hydrocarbyl radicals comprise from 1 to 12 carbon atoms, and a is an integer of from zero to 3, R.sub.2, R.sub.3 and R.sub.4 are each selected from the group consisting of H and OA, A is H or is selected from the group consisting of hydrocarbyl radicals, ##STR3## R.sub.5 is selected from the group consisting of hydrocarbyl radicals; n is an integer between 1 and 3; and R.sub.6 is an alkyl chain having between 1 and 3 carbon atoms with the provision that at least one of R.sub.2, R.sub.3 and R.sub.4 is H, that at least one of R.sub.2, R.sub.3 and R.sub.4 is not H, and that R.sub.2 and R.sub.4 are not both OA, and pharmaceutically acceptable salts thereof. Preferably, R.sub.2 is oxygen. Preferably, R.sub.2 is OA and A is H, and the compound is the (-) isomer.

Method and compositions for treatment of parkinsonism syndrome in mammels

Abnormalitites in the distribution of a dopamine D.sub.2 receptors in humans and other mammals are detected by

Method for detecting dopaminergic diseases using fluorine-18

This invention provides a method for treating the symptoms of parkinsonism which comprises administering to a human or other mammal suffering from the symptoms of parkinsonism an effective amount of a compound selected from the group consisting of optically-active or racemic compounds represented by the general formula: ##STR1## wherein R.sub.1 is selected from the group consisting of organic radicals methyl, substituted or unsubstituted phenyls, pyridyl, hydroxyphenyl, ##STR2## X is oxygen or sulfur, Y is selected from the group consisting of hydroxy, nitro, cyano, azido, amino, acylamino, carboxyamido, trifluoromethyl, sulfate, sulfonamido, halogen, hydrocarbyl and hetero atom-substituted hydrocarbyl radicals, wherein said heteroatoms are selected from the group consisting of halogen, nitrogen, oxygen, sulfur and phosphorus and said hydrocarbyl radicals comprise from 1 to 12 carbon atoms. and a is an integer of from zero to 3,

Method and compositions for treatment of parkinsonism syndrome in mammals

This invention provides a method for treating the symptoms of schizophrenia which comprises administering to a schizophrenic an effective amount of a compound selected from the group consisting of optically-active or racemic compounds represented by the general formula: ##STR1## wherein R.sub.1 is selected from the group consisting of organic radicals having fused rings, phenyl, pyridyl ##STR2## X is oxygen or sulfur, Y, if present, is selected from the group consisting of hydroxy, nitro, cyano, azido, amino, acylamino, carboxyamido, trifluoromethyl, sulfate, sulfonamido halogen, hydrocarbyl and hetero atom-substituted hydrocarbyl radicals, wherein said heteroatoms are selected from the group consisting of halogen, nitrogen, oxygen, sulfur and phosphorus and said hydrocarbyl radicals comprise from 1 to 12 carbon atoms, and a is an integer between zero and 3. R.sub.2, R.sub.3 and R.sub.4 are each selected from the group consising of H and OA, A is H or is selected from the group consisting of hydrocarbyl radicals, or ##STR3## R.sub.5 is selected from the group consisting of hydrocarbyl radicals and n is 2 or 3; with the proviso that at least one of R.sub.2, R.sub.3 and R.sub.4 is H, that at least one of R.sub.2, R.sub.3 and R.sub.4 is not H and that R.sub.2 and R.sub.4 are not both OA, except that when R.sub.1 is m-hydroxyphenyl, phenyl or 2-thienyl, the compound is optically-active.

Novel compounds useful as dopamine receptor agonists for the treatment of various diseases of the central nervous system such as Parkinson's disease and related disorders having the structural formula ##STR1## where R.sub.2, R.sub.3 and R.sub.4 are each selected from the group consisting of H, and OA; A is selected from the group consisting of hydrocarbyl radicals; ##STR2## where X is S or O: and pharmaceutically acceptable salts thereof. Also disclosed is a method for inducing a dopaminergic response in a patient by adminstering a pharmacologically-effective amount of one of the foregoing compounds.

The invention provides compounds represented by the general formula ##STR1## where R.sub.2, R.sub.3 and R.sub.4 are each selected from the group consisting of H, and OA; A is H or ##STR2## R.sub.5 is selected from the group consisting of alkyl and aromatic residues; n is 2 or 3; and R.sub.1 is selected from the group consisting ##STR3## wherein R.sub.6 is selected from the group consisting of halogen, hydrocarbyl and hetero atom-substituted hydrocarbyl, comprising from 1 to 12 carbon atoms and wherein said hetero-atoms are selected from the group consisting of halogen, nitrogen, oxygen, sulfur and phosphorus; R.sub.7 is R.sub.6 or H and m equals 1, 2 or 3; with the proviso that at least one of R.sub.2, R.sub.3 and R.sub.4 is H, that at least one of R.sub.2, R.sub.3 and R.sub.4 is not H and that R.sub.2 and R.sub.4 are not both OA; and pharmaceutically-acceptable salts thereof. The compounds are dopamine receptor agonists and useful for the treatment of glaucoma in mammals.

This invention provides a method for reducing the intraocular pressure in mammals which comprises administering an effective amount of a compound selected from the group consisting of compounds represented by the general formula: ##STR1## where R.sub.2, R.sub.3 and R.sub.4 are each selected from the group consisting of H, and OA; A is H or ##STR2## R.sub.5 is selected from the group consisting of alkyl and aromatic residues; n is 2 or 3; and R.sub.1 is selected from the group consisting of 3-hydroxyphenyl, 4-hydroxyphenyl, 3-pyridyl, 4-pyridyl, ##STR3## where X is S, O or NH, with the proviso that at least one of R.sub.2, R.sub.3 and R.sub.4 is H, that at least one of R.sub.2, R.sub.3 and R.sub.4 is not H and that R.sub.2 and R.sub.4 are not both OA; and pharmaceutically-acceptable salts thereof. This invention further provides compositions useful in such method of reducing the intraocular pressure in mammals.

Method and compositions for reducing the intraocular pressure of mammals

Novel compounds useful as dopamine receptor agonists for the treatment of various diseases of the central nervous system such as Parkinson's disease and related disorders having the structural formula ##STR1## where R.sub.2, R.sub.3 and R.sub.4 are each selected from the group consisting of H, and OA; A is H or ##STR2## R.sub.5 is selected from the group consisting of alkyl and aromatic residues; n is 2 or 3; and R.sub.1 is selected from the group consisting of 3-hydroxyphenyl, 4-hydroxyphenyl, 3-pyridyl, 4-pyridyl, ##STR3## where X is S, O or NH; and pharmaceutically acceptable salts thereof. Also disclosed is a method for inducing a dopaminergic response in a patient by adminstering a pharmacologically-effective amount of one of the foregoing compounds.

A method for inducing an anticurare response by administering 2,4-diaminopyridine to a mammal is disclosed, together with pharmaceutical compositions containing an effective amount of 2,4-diaminopyridine either alone or in combination with an anticholinesterase agent. 2,4-Diaminopyridine is an antagonist of muscle relaxants used in anesthesiology and can increase neuromuscular transmission in certain disease states.

2,4-Diaminopyridine as a pharmacologic agent

Compounds are disclosed having the formula: ##STR1## wherein: R.sub.1 is H, OH, --OCH.sub.3, --CH.sub.2 OH, --NH.sub.2, --NHMe, --NHEt, --NMe.sub.2, --NEt.sub.2, ##STR2## R.sub.2 is H, --CH.sub.3, or ##STR3## R.sub.3 is phenyl, benzyl, or 1-4 carbon alkyl; R.sub.4 is H, --CH.sub.3, --CH.sub.2 OH, --CH.sub.2 --CN, --CH.sub.2 --S--Me, CH.sub.2 --S--CN, or ##STR4## R.sub.5 is H, 1-4 carbon alkyl, alkenyl, or alkynyl, or aralkyl having a 1-4 carbon alkylene moiety; and A is --CH.sub.2 --or --CH.sub.2 CH.sub.2 --, and pharmaceutically-acceptable salts thereof. Pharmaceutical preparations using these compounds and a method for inducing a dopaminergic response by administering these compounds are also disclosed.

Dopamine agonists and use thereof

A method of selectively stimulating D-2 dopamine receptors in humans comprising administering to a human requiring D-2 dopamine receptor stimulation, a therapeutically effective amount of 2-(N-phenylethyl-N-propylamino)-5-hydroxytetralin or a pharmaceutically acceptable salt thereof.

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Noordhorn, Netherlands

Alan S Horn