In drug discovery research, the objectives of pharmacologystudies are to demonstrate the biologic activity (efficacy and selectivity) ofa new molecule entity (NME) against the targeted disease, and to provide data for safety evaluation. Thus, pharmacology studies can be divided into three categories: Primary pharmacodynamic (or primary pharmacology), Secondary pharmacology and Safety pharmacology studies.
Studies on the mode of action and/or effects of a test substance in relation to its desired therapeutic target are Primary Pharmacodynamics. Assessments of new drugs for pharmacological activities other than the desired therapeutic target are called Secondary Pharmacology. The third category, Safety Pharmacology studies investigate the potential undesirable pharmacodynamic effects of a test substance on physiological function of one ormore organ systems in relation to exposure in the therapeutic range and above.Thus, safety pharmacology studies contribute to risk assessment and patient management. For those who are interested in knowing more on Safety pharmacology studies may consult ICH guidance S7A (CNS, respiratory and CVS) and S7B (proarrhythmic risk)
(http://www.fda.gov/Drugs/
Sufficient information is not readily available on secondary pharmacology target (or off-target activity) of NME. E.g., agonist activity ofa NME to 5-HT2B receptors on heart valve leaflets is known to cause fibrotic cardiac valvulopathy. Ergot alkaloid (ergotamine), MDMA (ecstasy) has partial agonist activity toward this receptor. For more information, readers may read this review article, an excellent source of information on secondary pharmacology targets screening for a NME:
Bowes, J. et al. Reducing safety-related drug attrition: theuse of in vitro pharmacological profiling. Nature Rev. Drug Discov. 11, 909–922(2012).
In the recent issue of NatureDrug Discovery, we have discussed the usefulness of potential off-targetactivity of NMEs. These data may be made available along with primarypharmacology data to support first in human clinical trials.http://www.nature.com/
Studies on the mode of action and/or effects of a test substance in relation to its desired therapeutic target are Primary Pharmacodynamics. Assessments of new drugs for pharmacological activities other than the desired therapeutic target are called Secondary Pharmacology. The third category, Safety Pharmacology studies investigate the potential undesirable pharmacodynamic effects of a test substance on physiological function of one ormore organ systems in relation to exposure in the therapeutic range and above.Thus, safety pharmacology studies contribute to risk assessment and patient management. For those who are interested in knowing more on Safety pharmacology studies may consult ICH guidance S7A (CNS, respiratory and CVS) and S7B (proarrhythmic risk)
(http://www.fda.gov/Drugs/
Sufficient information is not readily available on secondary pharmacology target (or off-target activity) of NME. E.g., agonist activity ofa NME to 5-HT2B receptors on heart valve leaflets is known to cause fibrotic cardiac valvulopathy. Ergot alkaloid (ergotamine), MDMA (ecstasy) has partial agonist activity toward this receptor. For more information, readers may read this review article, an excellent source of information on secondary pharmacology targets screening for a NME:
Bowes, J. et al. Reducing safety-related drug attrition: theuse of in vitro pharmacological profiling. Nature Rev. Drug Discov. 11, 909–922(2012).
In the recent issue of NatureDrug Discovery, we have discussed the usefulness of potential off-targetactivity of NMEs. These data may be made available along with primarypharmacology data to support first in human clinical trials.http://www.nature.com/
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