A well-known hypnotic drug can turn out to be an effective remedy for the suffering of schizophrenia patients. Yet, it has one major drawback: its duration of action is only two-hours long. The researchers from the Jagiellonian University Medical College will try to modify its properties in order to better fit the needs of schizophrenics.
“Schizophrenia is an illness that affects about 1 percent of the global population. The sufferers hear voices and other sounds that cause fear and anxiety. They gradually withdraw from society, in which they can no longer function,” says Dr Monika Marcinkowska of the JU Medical College.
The modern medicine is capable of hindering the symptoms and muffling the voices by means of antipsychotic drugs. However, they are not an ideal solution since about 30 percent of patients do not respond to them at all. They also have many side-effects, which results in about 40 percent of patients rejecting pharmacotherapy.
Olanzapine is one of such medications. “As it enters the brain, it comes into contact with some receptors, suppressing voices and delusions of the patient. Yet, at the same time, it interacts with many other receptors, causing undesired effects, such as low blood pressure, sexual dysfunctions, weight gain, or memory disorders,” Dr Marcinkowska explains.
Hence, scientists are looking for novel therapeutic solutions that could help schizophrenics. However, as pointed out by Dr Marcinkowska, “discovering a new medicine and introducing it to the market usually takes about 15 years and costs about 1 billion dollars.”
One of the ways of shortening the long and arduous process of developing a new medicine is to use an already existing one for an entirely different purpose. This is the intention of the team led by Dr Monika Marcinkowska. “Our partners from the Institute of Psychiatry and Neurology in Warsaw have recently discovered that very low doses of a well-known hypnotic drug zolpidem cause antipsychotic effects when administered to experimental animals,” she explains.
It is possible to cause symptoms of psychosis in rats by giving them certain substances, e.g. amphetamine. As Dr Marcinkowska explains, “The animals are put into a state known as hyperlocomotion. Then the tested substance (in this case zolpidem) is administered and reversed hyperlocomotion is induced.” These are standard preclinical tests conducted to evaluate the effectiveness of a prospective antipsychotic.”
There is only one problem – zolpidem works for only two hours and this is much too short. The researcher stresses that “its short duration of action, which is an advantage for a hypnotic drug, is a serious disadvantage in case of a medicine for schizophrenia.”
Dr Marcinkowska’s research team has developed a number of modifications of this hypnotic drug, aimed at creating a “new, better zolpidem.” The duration of action is going to be adapted to the needs of schizophrenia patients. Besides, it will not have so many side effects as olanzapine, because it interacts with only one receptor in the brain. “The duration of action can be prolonged by modifying the chemical structure of drugs. Some chemical groups are introduced and some are removed,” the researcher explains.
It is also very important to check, if these chemical changes will improve the drug’s solubility in water. “Why is it so vital? A medicine entering the organism is transported to the brain via the bloodstream, and blood is 90 percent water. That is why the water solubility is so crucial for the expected pharmacological effect,” stresses Dr Marcinkowska.
To carry out her research project, Dr Marcinkowska has received PLN 120,000 from the Foundation for Polish Science, within the framework of Inter competition.
