A new synthetic chemical may provide framework for future drugs to treat brain-based ailments

May 19 2004

A new synthetic chemical may provide the framework for future drugs that can treat a variety of brain-based ailments, ranging from overeating and drug dependency to neuropathic pain.

Daniele Piomelli, professor of pharmacology at the UC Irvine College of Medicine, and colleagues at the University of Connecticut have created a molecule, AM1172, that regulates the processing of a neurotransmitter called anandamide. In tests on mice, Piomelli found AM1172 to be effective in increasing brain anandamide activity, in much the same way as the antidepressant drug Prozac increases activity of the neurotransmitter serotonin.

The study appears in the early online edition of the Proceedings of the National Academy of Sciences, May 10.

Anandamide is a natural marijuana-like compound that responds to hormones and external stimuli and activates cannabinoid receptors in the brain. This endocannabinoid system helps regulate pain, mood and appetite, along with dependence on drugs such as alcohol and marijuana. Because of this, anandamide is sometimes referred to as the “bliss” molecule.

According to Piomelli, AM1172 works by blocking anandamide degradation, boosting the actions of this natural transmitter without indiscriminately activating cannabinoid receptors in the brain, making it much more selective and effective at targeting specific receptors involved with specific behaviors.

“By understanding how this works at a biological level, we can begin to understand how anxiety and depression is connected with obesity and the dependence on substances such as marijuana,” said Piomelli, who also studies how anandamide and other similar substances are involved in feeding and obesity. “By helping the body’s own system give the brain a boost, compounds such as AM1172 might be able to counterbalance these feelings of anxiety and depression.”

Piomelli’s colleagues in the study included Darren Fegley and Satish Kathuria of UCI, and Richard Mercier, C. Li, Andreas Goutopolous and Alexandros Makriyannis of the University of Connecticut.

The study was funded by the National Institute of Drug Abuse.