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Flavonoids are widely consumed in the diet in food, beverages and herbal preparations. They have diverse actions on the body. We wish to investigate how they might affect brain function. One of the most important transmitters in the brain is a chemical known as GABA. Many known CNS drugs, such as alcohol and the benzodiazepine Valium, influence the action of GABA as a transmitter. These drugs enhance the action of GABA in activating particular receptors in the brain. We have discovered that apig ....Flavonoids are widely consumed in the diet in food, beverages and herbal preparations. They have diverse actions on the body. We wish to investigate how they might affect brain function. One of the most important transmitters in the brain is a chemical known as GABA. Many known CNS drugs, such as alcohol and the benzodiazepine Valium, influence the action of GABA as a transmitter. These drugs enhance the action of GABA in activating particular receptors in the brain. We have discovered that apigenin, a flavonoid found in many herbal preparations and in beverages such as camomile tea, has a special action on GABA in that it enhances the enhancing action of benzodiazepines on GABA receptors. This is a novel mode of drug action that needs to be explored further. We will study the actions of a range of flavonoids known to occur in various popular products such as soy milk, red wine and green tea for their effects on GABA receptors. From the results we plan to design and synthesise new substances with a view to discovering new therapeutic agents to treat a range of CNS disorders, such as anxiety, epilepsy and memory deficits. This project will also yield information on the possible interactions between alcohol and prescription drugs like Valium with flavonoids consumed in the diet. Already it is known that a flavonoid in grape fruit juice may influence the metabolism of drugs like Valium. This project will be concerned with possible interactions within the brain. The novel mode of action that we have discovered is of significance in terms of our basic understanding of brain function. It could add another dimension to what we already know about the brain as our most complex organ.Read moreRead less
Given that consumption of flavonoids in the diet is likely to be 100-1000 mg per day, it is important to find out how flavonoids might influence GABA-A receptors especially in relation to influencing actions of other therapeutic agents that interact with GABA-A receptors in the brain, such as benzodiazepines and ethanol. This may lead to new strategies in the use of herbal medicines and their possible interactions with other medications. These studies will provide information on how key dietary ....Given that consumption of flavonoids in the diet is likely to be 100-1000 mg per day, it is important to find out how flavonoids might influence GABA-A receptors especially in relation to influencing actions of other therapeutic agents that interact with GABA-A receptors in the brain, such as benzodiazepines and ethanol. This may lead to new strategies in the use of herbal medicines and their possible interactions with other medications. These studies will provide information on how key dietary flavonoids and novel structurally related chemicals could influence brain function. This project will probe the chemical characteristics of novel modes of action of flavonoid-related compounds in order to design and develop potentially useful therapeutic agents for CNS disorders involving GABA-A receptors. It is likely that flavonoids act on specific sites on such receptors that represent important new targets for drug development. This research is intended to provide new chemical entities useful as either alternatives to the benzodiazepines, which have a range of undesirable side effects, or as adjuncts to enable reduced doses of benzodiazepines to be used.Read moreRead less
MOLECULAR STRUCTURE-FUNCTION RELATIONSHIPS OF THE NORADRENALINE TRANSPORTER & DRUG ACTION
Funder
National Health and Medical Research Council
Funding Amount
$188,912.00
Summary
The transmission of impulses by nerves is dependent on the release of chemicals, termed neurotransmitters, from the nerve. The neurotransmitter causes its effects and then its action is usually terminated by membrane proteins that transport the chemical back into the nerve. These proteins are termed 'transporters'. In the brain, psychostimulants such as cocaine and also drugs that are used in the therapy of conditions such as depression block the activity of the transporters for the neurotransmi ....The transmission of impulses by nerves is dependent on the release of chemicals, termed neurotransmitters, from the nerve. The neurotransmitter causes its effects and then its action is usually terminated by membrane proteins that transport the chemical back into the nerve. These proteins are termed 'transporters'. In the brain, psychostimulants such as cocaine and also drugs that are used in the therapy of conditions such as depression block the activity of the transporters for the neurotransmitters, noradrenaline, serotonin and dopamine. Recently, the structures of the transporter proteins have been determined using molecular biology techniques. The focus of this project is to determine the parts of the noradrenaline transporter protein structure that are important in determining its functions, utilising the knowledge that we now have about its molecular structure. This will lead to exciting advances in understanding the function of the noradrenaline transporter and these advances should ultimately lead to the development of more effective antidepressant drugs and of drugs to prevent the effects of psychostimulants such as cocaine.Read moreRead less