Abstract: A method of treating disease-induced peripheral neuropathy comprises administering to a patient with disease-induced peripheral neuropathy an effective quantity of a purine derivative or analogue, a tetrahydroindolone derivative or analogue, or a pyrimidine derivative or analogue. If the compound is a purine derivative, the purine moiety can be guanine or hypoxanthine. The compound can induce peripheral nerve sprouting through the action of a neurotrophic factor such as nerve growth factor (NGF) without the occurrence of hyperalgesia. The peripheral nerve sprouting can be nociceptive nerve sprouting. The disease-induced peripheral neuropathy can be diabetic neuropathy or disease-induced peripheral neuropathy with another basis.

Abstract: Disclosed herein are methods and associated compositions and medicaments directed generally to the control of cellular and neural activity and for selectively and controllably inducing the in vivo genetic expression of one or more naturally occurring genetically encoded molecules in mammals. More particularly, the present invention selectively activates or derepresses genes encoding for specific naturally occurring molecules such as proteins or neurotrophic factors and induces the endogenous production of such naturally occurring compounds through the administration of carbon monoxide dependent guanylyl cyclase modulating purine derivatives. The methods of the present invention may be used to affect a variety of cellular and neurological functions and activities and to therapeutically or prophylactically treat a wide variety of neurodegenerative, neurological, cellular, and physiological disorders.

Abstract: Disclosed herein are methods directed generally to the control of neural activity and for selectively and controllably inducing the in vivo genetic expression of one or more naturally occurring genetically encoded molecules in mammals. More particularly, the present invention selectively activates or derepresses genes encoding for specific naturally occurring molecules such as neurotrophic factors through the administration of carbon monoxide dependent guanylyl cyclase modulating purine derivatives. The methods of the present invention may be used to affect a variety of cellular and neurological activities and to therapeutically or prophylactically treat a wide variety of neurodegenerative, neurological, and cellular disorders.

Abstract: Novel 9-substituted hypoxanthine derivatives with unexpected physiological effects are disclosed. These compounds are of formula (I) where n is an integer from 1 to 6, R1 is selected from the group consisting of H, COOH, and COOW1, where W1 is selected from the group consisting of lower alkyl, amino, and lower alkylamino, and R2 is selected from the group consisting of H and OH. Among these compounds are N-(2-(5-hydroxyindol-3-yl)ethyl-3-6-oxyhydropurin-9-yl)propanamide, N-2-(indol-3-yl)ethyl)-3-(6-oxyhydropurin-9-yl)propanamide and N-(1-carboxyl)-(2-(5-hydroxyindol-3-yl)ethyl-3-(6-oxyhydropurin-9-yl)propanamide. These compounds have a number of utilities, including inhibition of the activity of monoamine oxidases, treating obesity, lowering serum cholesterol, and increasing the level of HDL cholesterol. Also disclosed are pharmaceutical compositions and methods of use of the derivatives to treat a number of disorders or conditions.

Abstract: The present invention is directed to 9-substituted guanine derivatives in which the guanine moiety is linked to another moiety with physiological or pharmacological activity through a carboxamide linkage. The number of carbon atoms between the guanine moiety and the carboxamide linking group is typically from 1 to 6. In some cases, the chemical moieties can have carbon chains of different lengths within the moiety linked to guanine through the carboxamide linker. A large number of different chemical moieties can be linked to the guanine moiety. The invention also includes pharmaceutical compositions including the 9-substituted guanine derivatives and methods of use of the 9-substituted guanine derivatives.

Abstract: The present invention comprises a method of stimulating regeneration or survival of a mammalian motor neuron or of a mammalian sensory neuron comprising administering to a mammal an effective amount of a compound that is a 9-substituted hypoxanthine derivative linked through a linker to a p-aminobenzoic acid moiety or of a salt or prodrug ester of such a compound. Preferably, the compound is N-4-carboxyphenyl-3-(6-oxohydropurin-9-yl) propanamide. The invention also includes pharmaceutical compositions formulated for stimulation of regeneration of a mammalian motor neuron comprising the 9-substituted hypoxanthine derivative and a pharmaceutically acceptable carrier.

Abstract: Disclosed herein are methods directed generally to the control of neural activity and for selectively and controllably inducing the in vivo genetic expression of one or more naturally occurring genetically encoded molecules in mammals. More particularly, the present invention selectively activates or derepresses genes encoding for specific naturally occurring molecules such as neurotrophic factors through the administration of carbon monoxide dependent guanylyl cyclase modulating purine derivatives. The methods of the present invention may be used to affect a variety of cellular and neurological activities and to therapeutically or prophylactically treat a wide variety of neurodegenerative, neurological, and cellular disorders.

Abstract: Disclosed herein are methods directed generally to the control of neural activity and for selectively and controllably inducing the in vivo genetic expression of one or more naturally occurring genetically encoded molecules in mammals. More particularly, the present invention selectively activates or derepresses genes encoding for specific naturally occurring molecules such as neurotrophic factors through the administration of carbon monoxide dependent guanylyl cyclase modulating purine derivatives. The methods of the present invention may be used to affect a variety of cellular and neurological activities and to therapeutically or prophylactically treat a wide variety of neurodegenerative, neurological, and cellular disorders.

Abstract: Disclosed herein are methods directed generally to the control of neural activity and to the treatment of neural disorders. More particularly, the present invention is directed to methods for the modification of mammalian neural activity through the administration of carbon monoxide dependent guanylyl cyclase modulating purine derivatives. The methods of the present invention may be used to affect a variety of neurological activities and to therapeutically or prophylactically treat a wide variety of neurodegenerative and neurological disorders.

Abstract: Novel bi-functional pharmaceutical compounds, particularly novel 9-substituted hypoxanthines of the general formula: ##STR1## where R is a neurologically active moiety, are described as pharmaceutical agents for treating neuroimmunologic disorders in mammals. Novel methods for the utilization of these compounds are also disclosed. These compounds exhibit uniquely dose-dependent, synergistic biological properties and are particularly useful for treating interrelated physiological systems.