Method of using dopamine reuptake inhibitors and their analogs for treating diabetes symptoms and delaying or preventing diabetes-associated pathologic conditions
Inventors
Chen, Hao • Liu, Ming • Sathyamoorthy, Malathi • Su, Qi • Leary, Lisa • Zhong, Wayne Shaobin
Assignees
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Publication Number
US-9119843-B2
Publication Date
2015-09-01
Expiration Date
Abstract
Method of using dopamine reuptake inhibitors, e.g., sydnonimine derivatives, for the management of diabetic symptoms and associated complications or conditions, such as hyperglycemia and diabetic neuropathy.
Core Innovation
The invention relates to a method for treatment of symptoms of Type II diabetes and delay of onset or occurrence of pathologic conditions associated with Type II diabetes. The method is carried out by administering an amount of a dopamine reuptake inhibitor effective for the treatment and the delay. The pathologic conditions comprise at least one selected from diabetic sensory neuropathy, diabetic autonomic neuropathy, diabetic retinopathy, diabetic nephropathy and diabetic angiopathy.
The dopamine reuptake inhibitor is selected from specified sydnonimine derivatives and pharmaceutically acceptable salts. Exemplified named compounds include 3-(phenylpropyl)-sydnonimine-N-phenylcarbamoyl and multiple substituted 3-benzyl/sydnonimine-N-phenylcarbamoyl derivatives with defined substituent variations. The core chemical concept is the use of sydnonimine-based dopamine reuptake inhibitors as the therapeutic active agent.
The disclosed background links Type II diabetes to impaired dopaminergic/neurological function and catecholamine/dopamine reuptake inhibition, associating diabetic states with hyperglycemia and diabetic neuropathy-like outcomes. The disclosed examples include preclinical mouse study results in which dopamine reuptake inhibitor treatment normalizes blood glucose and attenuates diabetic hypoalgesia in hot-plate and tail-flick assays, supporting mitigation of sensory neuropathy-like outcomes.
Claims Coverage
The independent claim covers a method for treating symptoms of Type II diabetes and delaying onset or occurrence of diabetes-associated pathologic conditions. The inventive subject matter is focused on administering an effective amount of a dopamine reuptake inhibitor that is specifically defined as certain sydnonimine derivatives (or pharmaceutically acceptable salts), directed to the listed diabetes pathologic conditions.
Treatment and delay of Type II diabetes pathologic conditions with a dopamine reuptake inhibitor
A method for treatment of symptoms of Type II diabetes and delay of onset or occurrence of pathologic conditions associated with Type II diabetes in a patient in need thereof, wherein the diabetes-associated pathologic conditions comprise at least one selected from diabetic sensory neuropathy, diabetic autonomic neuropathy, diabetic retinopathy, diabetic nephropathy and diabetic angiopathy, consisting essentially of administering an amount of a dopamine reuptake inhibitor that is effective for said treatment and said delay.
Sydnonimine derivative dopamine reuptake inhibitors for the method
The dopamine reuptake inhibitor is a compound selected from the group consisting of 3-(phenylpropyl)-sydnonimine-N-phenylcarbamoyl, 3-(p-methylbenzyl)-sydnonimine-N-phenylcarbamoyl, 3-(p-carboxybenzyl)-sydnonimine-N-phenylcarbamoyl, 3-(p-fluorobenzyl)-sydnonimine-N-phenylcarbamoyl, 3-(3′,5′-difluorobenzyl)-sydnonimine-N-phenylcarbamoyl, 3-(m-fluorobenzyl)-sydnonimine-N-phenylcarbamoyl, 3-(p-trifluoromethyl-benzyl)-sydnonimine-N-phenylcarbamoyl, 3-(p-tert-butylbenzyb-sydnonimine-N-phenylcarbamoyl, 3-(p-methylbenzyl)-sydnonimine-N-(p′-trifluoromethyl-phenyl)carbamoyl, and 3-(p-methylbenzyl)-sydnonimine-N-(p-dimethylamino-phenyl)carbamoyl, and the pharmaceutically acceptable salts of said compound.
Use of 3-(phenylpropyl)-sydnonimine-N-phenylcarbamoyl or pharmaceutically acceptable salts
The dopamine reuptake inhibitor is 3-(phenylpropyl)-sydnonimine-N-phenylcarbamoyl, or a pharmaceutically acceptable salt thereof.
Across the independent claim coverage, the invention is directed to delaying the onset or occurrence of Type II diabetes-associated pathologic conditions and treating diabetes symptoms by administering an effective amount of a dopamine reuptake inhibitor defined as specific sydnonimine derivative compounds (and pharmaceutically acceptable salts), including 3-(phenylpropyl)-sydnonimine-N-phenylcarbamoyl.
Stated Advantages
Treats symptoms of Type II diabetes.
Delays onset or occurrence of pathologic conditions associated with Type II diabetes.
Normalizes blood glucose in disclosed preclinical mouse study results.
Attenuates diabetic hypoalgesia in hot-plate and tail-flick assays, supporting mitigation of sensory neuropathy-like outcomes.
Documented Applications
A method for treatment of symptoms of Type II diabetes in a patient in need thereof.
A method for delay of onset or occurrence of diabetes-associated pathologic conditions including diabetic sensory neuropathy, diabetic autonomic neuropathy, diabetic retinopathy, diabetic nephropathy and diabetic angiopathy.
Preclinical mouse study application using a high fat diet hyperglycemia model with hot-plate and tail-flick assays for disclosed outcomes.
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