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
The Pharmacology And Physiology Of GABA-C Receptors
Funder
National Health and Medical Research Council
Funding Amount
$481,980.00
Summary
GABA is one of the most important chemicals in the brain. GABA and its associated receptors (GABA receptors) work together to keep the balance between neuronal excitation and inhibition which is required for normal brain function. There are three types of GABA receptors called GABA-A, GABA-B and GABA-C receptors. Chemicals acting at these receptors may be therapeutically useful in treating neurological probles such as epilepsy, anxiety, depression and memory-related disorders associated with Alz ....GABA is one of the most important chemicals in the brain. GABA and its associated receptors (GABA receptors) work together to keep the balance between neuronal excitation and inhibition which is required for normal brain function. There are three types of GABA receptors called GABA-A, GABA-B and GABA-C receptors. Chemicals acting at these receptors may be therapeutically useful in treating neurological probles such as epilepsy, anxiety, depression and memory-related disorders associated with Alzheimer's disease and schizophrenia. GABA-A and GABA-C receptors are members of the ligand-gated ion channel super family in which the ion channel forms an intergral and central part of the receptor. In response to GABA, the channel opens and chloride ions flow through the channel. This causes an inhibitory action i.e. the cell reduces its rate of firing. This project aims to study GABA-C receptors by investigating what proteins make up the ion channel, by studying the actions of a range of chemicals that have specific effects at these receptors and by identifying amino acids that are important for normal channel function. New chemicals identified in our studies will provide leads for the design and development of new therapeutic agents acting on the brain.Read moreRead less