Thiazolidinediones (TZDS) are a class of drugs which are commonly prescribed for the treatment of type 2 diabetes, Fibrates are a class of similar structurally drugs are prescribed to modulate the levels of lipid in diabetic patients and diabetics to help reduce the risk of cardiovascular disease. These drugs work to connect receptors to apply on peroxisome (PPAR), TZDS reduced resistance to insulin and reduced levels of cytokines that promote inflammation and Fibrates reduction of lipoproteins of low density (LDL) and triglycerides and increase high-density (HDL) lipoprotein levels to help prevent cardiovascular diseases.
Another effect of TZD and Fibrates is to raise the levels of leptin, an effect which can reduce appetite. Recent studies also indicate that the PPAR is expressed in the central nervous system, especially in areas of the brain involved in the reward.
Two documents recently published in Biological Psychiatry now suggest that the drugs that stimulate the two subclasses of PPAR, PPAR and PPAR-g, can play a role in the treatment of dependence, nicotine and alcohol acting on the brain.
The first study, of Mascia and his colleagues, used a collaborative approach to demonstrate that the addictive effects of nicotine can be offset by drugs that activate PPAR-a. In rats and monkeys, these drugs intake reduces nicotine and nicotine relapse and they seek after a period of abstinence. It also prevents nicotine altering the electrical activity and neurochemical levels in the areas of the brain of drug addicts.
"With our highly selective experimental drug research, there are drugs (Fibrates) used clinically for the treatment of high cholesterol and triglycerides, which are selective ligand of PPAR-a," explains lead author Dr. Steven Goldberg. "Drugs that selectively affect the receptor PPAR-a, perhaps including the Fibrates, would give a new approach of value for the treatment of addiction to nicotine in human beings."
In the second study, Stopponi and his colleagues used pioglitazone to assess their impact on the consumption of alcohol, relapse behavior and removal in rats. Pioglitazone activates PPAR-g and it is a drug approved by the FDA for the treatment of type 2 diabetes.
Corresponding author Dr. Roberto Ciccocioppo detailed their findings, "we have shown that the activation of PPAR-g receptors by voluminous pioglitazone reduced the consumption of alcohol in a model rat of excessive alcohol consumption." "We also discovered pioglitazone suppresses the craving for alcohol and exposure to stress and prevent the signs of the somatic expression of alcohol withdrawal."
"As we learn more about the brain, we are witnessing an increasing number of examples where a drug initially developed for purposes not related to psychiatry can have new applications and otherwise unexpected psychiatric results ." In this case, the identification of the PPAR neural circuits suggested reward of new functions for the PPAR pacemakers. These new data in animal models suggest that it might be TZDS, promising new agents in the fight against drug abuse, "said Dr. John Krystal, editor of Biological Psychiatry.
It is important to note that these first interesting conclusions are only measures from the beginning of a line of research which must take place before TZDS or Fibrates may be used in a clinical environment to treat people with dependencies.
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