In preclinical studies, researchers at SRI International and Astraea
Therapeutics have recently evaluated the role of a new drug receptor target
that shows promise for the treatment of drug addiction.
This potential new drug target belongs to a class of receptors called the
nicotinic acetylcholine receptors (nAChRs). One subtype of nAChRs, called
alpha4beta2, is a well-known target for nicotine’s addictive effects and the
therapeutic effect of the smoking cessation drug varenicline. SRI researchers
are now studying another, lesser-known subtype, called alpha3beta4 nAChR, which
has recently shown to play a role in the addictive properties of cocaine,
morphine, and nicotine.
Using AT-1001, a highly selective alpha3beta4 compound developed by Astraea
Therapeutics, SRI researchers found that addiction processes could be
disrupted. In preliminary studies, AT-1001 also reduced nicotine withdrawal
symptoms such as anxiety.
Because addictive drugs act on the brain’s “reward circuit,” many
people compulsively take them despite their harmful consequences. Feelings of
pleasure are caused by the release of brain chemicals, or neurotransmitters,
and their increased activity in the brain reward circuit. The key
neurotransmitter in the reward circuit is dopamine, which produces changes in
addictive behavior. Researchers speculate that disruption of the alpha3beta4
nAChR system using highly selective drugs such as AT-1001 may interrupt this
reward circuitry.
“Currently, there are no therapeutics approved to treat addiction to
stimulants such as cocaine, so it is intriguing to find a promising drug
receptor target and to see that AT-1001 can indeed affect phenomena that are
thought to be deeply tied to the addictive nature of cocaine and other drugs of
abuse,” said Taline Khroyan, PhD, senior behavioral pharmacologist in SRI’s
Center for Health Sciences.
