Experimental drug found to reduce nicotine craving

September 13, 2012 by Bob Yirka report

(Medical Xpress)—Researchers at the Aptuit Centre for Drug Discovery and Development in Italy, have found that a drug called GSK598809 is able to block a type of dopamine receptor in the brain that has been linked to nicotine addiction. The team, studying the impact of the drug on baboons and mice has found, as they describe in their paper published in the journal Neuropsychopharmacology, that when delivered to the brain, the drug appears able to reduce the cravings for nicotine found in the smoke of cigarettes and thus may someday soon serve as an aide to quitting the habit that kills millions the world over every year.

As with most addictions, the root cause of an addiction to nicotine is that it causes the release of dopamine into the brain which is picked up by receptors. Over time the brain comes to expect the small dose to arrive in regular intervals and when it stops, severe cravings result that that make it extremely difficult to ignore. The result for many people is a long, lung destroying habit.

In this new research the team working out of a lab formerly owned by British drug-making giant, GlaxoSmithKline, tested the drug on baboons and rats by first getting them addicted to nicotine and then giving them GSK598809. They followed that up by performing which allowed them to see the actual impact of both the nicotine and drug on the brain. The results have been so promising that the team reports that they are now ready to begin clinical trials with people.

This new research was built on previous studies that showed that nicotine increased the release of dopamine into the pallidum, ventral and midbrain, the that are now believed to be involved in . GSK598809 doesn't prevent this from happening, but instead causes the that react (D3 receptors) to not be so sensitive to its presence. Performing brain imaging allowed the researchers to see that the drug was making it to where it was supposed to go in the brain and to chart the amount of sensitivity that came about as a result; and because of this, the researchers were able to fine tune the amount of the drug needed to dull the addictive cravings in humans and actually ran a few test trials which they report did indeed reduce cravings in smokers.

The researchers say they believe GSK598809, once it undergoes more thorough testing, will one day be added to the list of drugs currently used to help people quit smoking and because it will prevent the associated cravings, will also help prevent relapse which is so common among those that try to quit.

Explore further: Moderate levels of secondhand smoke deliver nicotine to the brain

More information: Occupancy of Brain Dopamine D3 Receptors and Drug Craving: A Translational Approach, Neuropsychopharmacology, (12 September 2012) | doi:10.1038/npp.2012.171

Abstract
Selective dopamine D3 receptor (D3R) antagonists prevent reinstatement of drug-seeking behavior and decrease the rewarding effects of contextual cues associated with drug intake preclinically, suggesting that they may reduce drug craving in humans. GSK598809 is a selective D3R antagonist recently progressed in Phase I trials. The aim of this study was to establish a model, based on the determination of the occupancy of brain D3Rs (OD3R) across species, to predict the ability of GSK598809 to reduce nicotine-seeking behavior in humans, here assessed as cigarette craving in smokers. Using ex vivo [125I](R)-trans-7-hydroxy-2-[N-propyl-N-(3′-iodo-2′-propenyl)amino] tetralin ([125I]7OH-PIPAT) autoradiography and [11C]PHNO positron emission tomography, we demonstrated a dose-dependent occupancy of the D3Rs by GSK598809 in rat, baboon, and human brains. We also showed a direct relationship between OD3R and pharmacokinetic exposure, and potencies in line with the in vitro binding affinity. Likewise, GSK598809 dose dependently reduced the expression of nicotine-induced conditioned place preference (CPP) in rats, with an effect proportional to the exposure and OD3R at every time point, and 100% effect at OD3R values 72%. In humans, a single dose of GSK598809, giving submaximal levels (72–89%) of OD3R, transiently alleviated craving in smokers after overnight abstinence. These data suggest that either higher OD3R is required for a full effect in humans or that nicotine-seeking behavior in CPP rats only partially translates into craving for cigarettes in short-term abstinent smokers. In addition, they provide the first clinical evidence of potential efficacy of a selective D3R antagonist for the treatment of substance-use disorders.

Related Stories

Moderate levels of secondhand smoke deliver nicotine to the brain

May 2, 2011
Exposure to secondhand smoke, such as a person can get by riding in an enclosed car while someone else smokes, has a direct, measurable impact on the brain—and the effect is similar to what happens in the brain of the ...

Nicotine vaccine prevents nicotine from reaching the brain

May 2, 2012
If smoking a cigarette no longer delivers pleasure, will smokers quit? It's the idea behind a nicotine vaccine being created by MIT and Harvard researchers, in which an injection of synthetic nanoparticles prompts the immune ...

Eliminating protein in specific brain cells blocks nicotine reward

July 26, 2011
Removing a protein from cells located in the brain's reward center blocks the anxiety-reducing and rewarding effects of nicotine, according to a new animal study in the July 27 issue of The Journal of Neuroscience. The findings ...

Recommended for you

Researchers find monkey brain structure that decides if viewed objects are new or unidentified

August 18, 2017
A team of researchers working at the University of Tokyo School of Medicine has found what they believe is the part of the monkey brain that decides if something that is being viewed is recognizable. In their paper published ...

Artificial neural networks decode brain activity during performed and imagined movements

August 18, 2017
Artificial intelligence has far outpaced human intelligence in certain tasks. Several groups from the Freiburg excellence cluster BrainLinks-BrainTools led by neuroscientist private lecturer Dr. Tonio Ball are showing how ...

Study of nervous system cells can help to understand degenerative diseases

August 18, 2017
The results of a new study show that many of the genes expressed by microglia differ between humans and mice, which are frequently used as animal models in research on Alzheimer's disease and other neurodegenerative disorders.

How whip-like cell appendages promote bodily fluid flow

August 18, 2017
Researchers at Nagoya University have identified a molecule that enables cell appendages called cilia to beat in a coordinated way to drive the flow of fluid around the brain; this prevents the accumulation of this fluid, ...

Researchers make surprising discovery about how neurons talk to each other

August 17, 2017
Researchers at the University of Pittsburgh have uncovered the mechanism by which neurons keep up with the demands of repeatedly sending signals to other neurons. The new findings, made in fruit flies and mice, challenge ...

Neurons involved in learning, memory preservation less stable, more flexible than once thought

August 17, 2017
The human brain has a region of cells responsible for linking sensory cues to actions and behaviors and cataloging the link as a memory. Cells that form these links have been deemed highly stable and fixed.

2 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

Tausch
not rated yet Sep 13, 2012
In this new research the team working out of a lab formerly owned by British drug-making giant, GlaxoSmithKline...


This is Anerkennung.(Tribute)
The purpose of the tribute escapes me.
Shootist
1 / 5 (1) Sep 13, 2012
In this new research the team working out of a lab formerly owned by British drug-making giant, GlaxoSmithKline...


This is Anerkennung.(Tribute)
The purpose of the tribute escapes me.


This is fear mongering and conspiracy building.
The purpose of the which escapes me.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.