Pharmocogenetics

Section Head

Dr. Rachel Tyndale

Contact

Dr. Rachel Tyndale
Department of Pharmacology
University of Toronto
1 King's College Circle
Toronto, Ontario M5S 1A8

Research Objective

The genetic risk for drug dependence is investigated using both pharmacogenetics and pharmacokinetics approaches. The long-term goal is to understand the mechanisms involved in drug abuse and optimize treatment for drug dependence by identifying the choice of drug and dosage that will be most effective.

Summary of Activities

Genetic variations in drug metabolism play a major role in altering responses to drugs of abuse, which include nicotine, alcohol, opiates, benzodiazepines, and amphetamines, as well as treatment drugs. Scientists have identified specific genes and enzymatic pathways that alter risk for drug taking behaviours. For example, genetic differences in nicotine metabolism alter risk for smoking, amount smoked, ability to quit, and risk for cancer. They also alter the usage and efficacy of nicotine replacement therapies and drugs such as Zyban. Using this information, scientists can mimic the genetic protection using enzyme blockers to develop novel treatments.

Another important area of research is investigating the role of cytochrome P450 (CYP) enzymes in the brain and how they might alter drug response and toxin effects.  Scientists are investigating the unique regulation, function and toxicity of CYP enzymes in the central nervous system (CNS). For drugs that act within the brain, changes in their metabolism may alter the pharmacological effect(s) and toxicity. These enzymes are regulated differently from the forms in the liver, and may play an important role in determining a patient's response to pharmacotherapy. Using cellular and animal models, as well as human in vivo and in vitro studies, scientists are providing insights into the role of CNS enzymes in brain function, response to drugs and neurotoxicity. Scientists hope to manipulate the function of the CNS enzymes that control responses to drugs and toxins, to reduce the risk of drug dependence/disease and improve treatment outcomes. The research findings may also enable scientists to identify novel targets for new drug development.

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