August 17, 2004

Can the receptor for nicotine be a target for a new drug?

Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia

Laura F. Martin, William R. Kem and Robert Freedman

Psychopharmacology (Berl). 2004 Jun;174(1):54-64. Epub 2004 Feb 19.

People with schizophrenia have long been known to have high rates of cigarette smoking compared to the rest of the population. While many theories abound regarding the reason, it has been shown that people with schizophrenia often have a different reaction to nicotine in their brain compared to people without schizophrenia. This reaction to nicotine occurs at the nicotinic receptor. One thought is that nicotine may help with some of the difficulty people with schizophrenia have in regulating sensation. Many with schizophrenia have problems in sorting out important from unimportant stimuli. This ability is called "gating" and the authors of this study argue that perhaps nicotine (and also clozapine) may help improve this gating phenomenon in people with schizophrenia and therefore the nicotinic receptor may be a target for future medications to help with this problem.

So far, a prototype drug (called DMXBA) has been shown to have some benefit on learning and memory in mice (they are able to do a maze and a couple of other tasks seemingly better with this medicine.) To this point, it has shown this possible benefit in mice and has appeared to be safe for use in mice (though humans often react differently to medicines than mice.) There has been one study published with the prototype drug that showed some improvement in simple memory and organizational tasks for humans. Though there have only been small studies thus far, it appears that side effects are similar to placebo (sugar pill) even at doses higher than would be used for treatment. There were a few people who had a negative reaction in their liver (increased liver enzymes) as a result of this medication and clearly, larger studies would need to be done to evaluate safety in a larger population.

Overall, this may be a potential new target of therapy. Most likely, a drug of this type would not be used for the complete treatment of schizophrenia, but may help in addition to regular antipsychotic treatment. However, it will take some more years of research to further evaluate the safety and effectiveness of this type of medication before it can come to market.

This work was supported by the VA Medical Research Service, USPHS MH-61412, NARSAD, the Stanley Foundation, and the Institute for Children s Mental Disorders.

Click here for link to article on Pubmed

Author: Jacob Ballon


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