Sunday, January 23, 2005

Drug That 'Tags' Decision-making Areas Of The Brain May Aid Battle Against Nicotine Addiction, Alzheimer's And Other Disorders

Along with aiding efforts to study addicted smokers, a new drug that attaches only to areas of the brain that have been implicated in nicotine addiction may help studies of people battling other disorders such as Alzheimer’s disease and schizophrenia.

Developed by UC Irvine Transdisciplinary Tobacco Use Research Center scientists, the new drug – Nifrolidine – is a selective binding agent that identifies specific areas of the brain responsible for decision-making, learning and memory. Lead researcher Jogeshwar Mukherjee, UCI associate professor of psychiatry and human behavior, developed Nifrolidine to measure a subtype of nicotine receptors in the living brain by using an imaging technique, positron emission tomography, more commonly known as PET scans. After proving the drug’s effectiveness, Mukherjee believes the drug will have implications for other conditions, as well.

Study results appear in the January issue of the Journal of Nuclear Medicine.

“Nifrolidine is suited to provide reliable, quantitative information of these receptors and may therefore be very useful for future human brain imaging studies of nicotine addiction and other clinical conditions in which these brain regions have been implicated,” Mukherjee said.

He found in animal tests that Nifrolidine binds to receptors in the temporal and frontal cortex, areas that are responsible for learning and memory as well as reasoning, planning, problem solving and emotion. According to Mukherjee, patients with Alzheimer’s disease have been known to have a 30 percent to 50 percent loss of these receptors “If there is a gradual loss of these receptors over time, Nifrolidine could be a potential marker for early diagnosis of Alzheimer’s disease,” Mukherjee said.

Scientists have known that nicotine’s action on these receptors elicits dopamine in various brain regions implicated in nicotine addiction and other disorders. Nicotine acts by opening specific membrane proteins, called nicotinic receptors, and changing the electrical properties of the cell.

The human brain coordinates billions of neurons to mediate complex behaviors such as an infant learning to recognize his or her parents, a senior citizen learning to play piano, or the process of addiction following repetitive exposure to specific drugs. These behaviors all result from the formation of new connections between individual neurons or modifications of existing connections in the brain.

“Imaging of nicotine receptors also gives us the potential to study why some people are more addicted to nicotine than others,” Mukherjee said.

Additional information : Chattopadhyay S, Xue B, Collins D, Pichika R, Bagnera R, Leslie FM, Christian BT, Shi B, Narayanan TK, Potkin SG, Mukherjee J.
Synthesis and Evaluation of Nicotine {alpha}4{beta}2 Receptor Radioligand, 5-(3'-18F-Fluoropropyl)-3-(2-(S)-Pyrrolidinylmethoxy)Pyridine, in Rodents and PET in Nonhuman Primate. Journal of Nuclear Medicine. 2005 Jan; 46(1): 130-140.

Source : University of California, Irvine



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