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MAILMAN RESEARCH CENTER

Bio-Organic and Natural Products Research Laboratory

The Bio-Organic and Natural Products Researchers

The Bio-Organic and
Natural Products Researchers
(click to enlarge)

This medication development program focuses on the discovery and development of pharmacotherapies for the treatment of alcohol and drug abuse and provides analytical chemistry support for clinical studies at McLean Hospital.

Over the past decade, research on possible pharmacotherapies for the treatment of alcohol and drug abuse has burgeoned. For instance, naltrexone, an opioid receptor antagonist, was recently approved in the United States for the treatment of alcohol-dependent patients. However, naltrexone can produce liver toxicity, and compliance has been a problem. Therefore, a greater research effort is needed to develop agents with less side-effect liability.

Our strategy is to investigate Chinese herbal remedies traditionally used for the treatment of alcohol and drug abuse. As evidenced in our study, puerarin, an isoflavone-C-glycoside isolated from Pueraria lobata, reduces alcohol drinking in alcohol preferring rats and monkeys and shows significant improvement of the withdrawal syndrome in alcoholic rats models. The naturally occurring progesterone metabolite allopregnanolone, a potent modulator of the GABAA receptor, has profound effects on stress, anxiety, and alcohol- and drug-seeking behavior.

Preliminary results from our laboratories show that certain synthetic analogs of allopregnanolone with improved half-life can stimulate Cl- uptake in synaptoneurosomes, protect against bicuculline-induced seizures in alcohol dependent rats, and reduce alcohol intake in alcohol preferring rats. Collectively, it appears that this class of compound might indeed yield some of the most potent GABAA-active agents with clinical significance. Other natural products, such as huperzine A, a potent acetylcholinesterase inhibitor isolated from the Chinese herb Huperzia serrata, are being evaluated for Alzheimer's disease.

Keywords

Isoflavone-C-glycosides, neurosteroids, anti-craving agents, alcohol drinking, pharmacokinetics, drug metabolism, pharmacotherapies.

Grant Support

Program Director

Program Personnel

Contact Person

Ann Miller, Administrative Assistant
Tel. (617) 855-2060
Fax (617) 855-3479

Representative Publications

04.2010