Drug Tackles Nicotine Addiction

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Associate Professor of Psychiatry and Human Behavior Jogeshwar Mukherjee has led the UC Irvine Transdisciplinary Tobacco Use Research Center scientists in the development of a new drug, Nifrolidine, which shows promise in the battle against nicotine addiction, as well as schizophrenia, Alzheimer’s and Parkinson’s diseases.
The team of scientists created Nifrolidine in order to tag specific receptors in the brain to which nicotine binds. These areas of the brain deal with learning, memory, reasoning, planning, problem solving and emotion.
Researchers hope that Nifrolidine may inhibit nicotine from entering into these receptor sites in the brain.
‘If you inject Nifrolidine into a person who has been smoking, nicotine and Nifrolidine will compete for the receptor sites,’ Mukherjee said. ‘Nicotine binds to the receptors and releases dopamine, which has been known to be involved in addiction. One of our potential applications is to use this agent to study why certain people get addicted and what is the status of nicotine’s interaction with the receptors.’
Mukherjee explained how their research came about.
‘We designed the molecule and then synthesized it,’ Mukherjee said. ‘The intention was to study the particular nicotine receptor subtype … that is involved in various neurotransmitter effects.’
The recent discoveries can be applicable in many different studies.
‘Another application we are interested in is in Alzheimer’s patients,’ Mukherjee said. ‘They have been shown to have lost a significant amount of these receptors. If we can evaluate these patients early on and diagnose them, we can intervene early. We may also be able to diagnose cancer earlier with more sensitive markers.’
Nifrolidine has also shown to be useful in studies of schizophrenia.
‘Compared to the current population, schizophrenics smoke two to three times more,’ Mukherjee said. ‘It is possible that the tendency to smoke is involved with the receptors.’
Studies with the drug have already been performed on monkeys at the Kettering Medical Center in Ohio. At UCI, researchers have also tested this method on rats.
In these tests, the animals lie down on a bed and are injected intravenously with a sterile saline solution containing Nifrolidine. The Nifrolidine binds to the receptors and emits isotopes that can be detected by PET scanners. Researchers are then able to see where the receptors that nicotine binds to are located in the brain.
The TTURC is interested in looking at nicotine and understanding why some people have a predisposition to it.
Mukherjee estimates it will take at least five years before the recent discoveries will affect the public.
‘We have to do some more studies and then get approval for human research,’ Mukherjee said. ‘Then we’ll have to do some more studies to demonstrate its indications. Once this is done, we will be able to apply it to other conditions, as well. … It is a good agent to pursue for potential use in clinical studies.’
He also noted the wide range of applications for the molecule.
‘There are many different study designs that one can use with the chemistry of Nifrolidine,’ Mukherjee said. ‘We can see dosages of
nicotine and how well nicotine interacts with a person’s receptors. We can study the differences between subjects. We can also tag their receptors before and after they smoke to see the differences there. We can also research different craving physiologies.’
Before the FDA approves studies on human subjects, two research steps must be completed.
‘We need to identify resources to do toxicity studies in two classes of animals,’ Mukherjee said. ‘Then we will have to do dosimetry to see how much radiation a patient will get. These are two elements that are needed to receive an FDA approval to start human studies. We are also looking at other agents that might be more effective than Nifrolidine.’

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