Biological Sciences

The Department of Pharmacology at Merck Frosst Centre for Therapeutic Research currently supports drug discovery programs focused on the development of therapeutics for diabetes, inflammation and neurodegeneration.

Pharmacologists at Merck Frosst play an essential role in drug discovery by developing animal models of human disease that enable the identification and characterization of new drugs. Increasing use of in vitro techniques in the drug discovery process has led to a reduction in the use of laboratory animals, but some studies are still mandatory before a new drug can be tested on humans. We continually strive to minimize animal use and adopt validated alternative methods whenever possible. We also support and conduct research to develop such alternatives. All our procedures and standards of animal care meet or exceed national and international regulations.

Once a disease model has been established, pharmacologists determine the relationship between drug concentration and a specific physiological outcome. In this way, animal studies are used to predict therapeutic doses for new compounds and estimate the corresponding safety window between possible efficacy and the potential for serious adverse effects. This information is critical to the selection of safe doses that can be studied in human clinical trials.

Molecular biology has revolutionized the process of drug discovery by enabling the precise control of the expression of drug targets, such as receptors and enzymes, in both cell lines and animals. Drug discoverers are now better able to create small molecules that interact with a specific receptor or enzyme, allowing the development of safer and more effective medications.

The advent of molecular biology has also permitted scientists to identify gene mutations responsible for a host of human genetic diseases. Using this information, researchers can generate mice that serve as genetic disease models for disorders such as diabetes, arthritis and Alzheimer's disease. These genetic models now play an important role in drug discovery by allowing researchers to assess the effectiveness of potential new therapeutics in a relevant animal model.

Using such genetic mouse models, Merck Frosst pharmacologists and McGill University scientists have demonstrated that it may be possible to treat type 2 diabetes (also know as non-insulin dependent diabetes mellitus) using drugs that block an enzyme known as PTP-1B. Genetically altered mice that lack PTP-1B are healthy, lean and have enhanced insulin sensitivity suggesting that drugs which inhibit this enzyme may be useful in the treatment of diabetes.

For the development of SINGULAIR^®, our pharmacologists were able to provide essential structure/activity data, and build the crucial bridge between theoretical chemistry, and clinical trials in humans. The team used animal models of asthma and allergy to characterize the effectiveness of each experimental leukotriene receptor antagonist, and its pharmacokinetic and functional activity data--information that allowed chemist to optimize the pharmacodynamics properties of the molecule. Pharmacologists selected animal species that had a similar balance of asthmatic mediators to that in humans--a predominance of leukotrienes. These models subsequently proved to be highly predictive of the therapeutic effects of SINGULAIR^® in humans enabling the reliable determination of doses that proved to be sage and efficacious in clinical trials.

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