Pharmacologic quantitation.
Either in vivo or in vitro quantitatives comparisons of drugs based on the dose-response relations were known for a long time. For therapeutically targeted molecular structure activity studies, agonists are simply compared on the basis of concentrations eliciting half-maximum response (EC50) and per cent maximum response elicited by drugs in the given system. For partial agonists the receptor affinity determined as the dissociation constant (KA) in homogenates corresponds to that in the organ system. However, due to the presence of spare receptors the EC50 of potent agonists does not represent the KA. If a fraction of receptors are irreversibly inactivated in the tissue, KA as well as relative intrinsic efficacy of the potent agonists can be obtained. Although quantitation of irreversible antagonists is quite complex, the competitive reversible blockers can be accurately compared on the basis of equilibrium dissociation constant (KB) values. Along with the relative order of potency of agonists and KB values of antagonists, receptors can be characterized and subclassified. Preclinical Therapeutic Index of drugs and Toxicity Index of pesticides require determinations of mean lethal dose (LD50) and the mean effective dose (ED50) in laboratory animals, so that a relatively safe drug can be promoted for human use. The understanding of pharmacokinetics is essential to explain drug action in the target organs. Drug combinations are investigated by isobolorographic analysis.
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Division of Pharmacology, College of Pharmacy (Parks Hall), Ohio State University, Columbus 43210, USA.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D006801:Humans; D007928:Lethal Dose 50; D010600:Pharmacology / Q000706:statistics & numerical data*; D011956:Receptors, Cell Surface / Q000187:drug effects
D011956:Receptors, Cell Surface