Graded dose-response curve

Anticonvulsants can be suitably studied by use of quantal dose-response curves. For example, to assess the potential of new anticonvulsants to control epileptic seizures in humans, these drugs are initially tested for their ability to protect animals against experimentally induced seizures. In the presence of a given dose of the drug, the animal either has the seizure or does not that is, it either is or is not protected. Thus, in the design of this experiment, the effect of the drug (protection) is all or none. This type of response, in contrast to a graded response, must be described in a noncontinuous manner. 

Dose-response curves illustrating the graded responses of five guinea pigs (a-e) to increasing doses of levarterenol. The responses are increases in heart rate above the rate measured before the administration of the drug. Broken lines indicate 50% of maximum response (horizontal) and individual ED50 values (vertical). 

Graded dose-response curves for four drugs, illustrating different pharmacologic potencies and different maximal efficacies. (See text.)... 

Finally, note that the quantal dose-effect curve and the graded dose-response curve summarize somewhat different sets of information, although both appear sigmoid in shape on a semilogarithmic plot (compare Figures 2-15 and 2-16). Critical... 

Dose-response curves to norepinephrine in the presence of two different a-adrenoceptor-blocking drugs. The tension produced in isolated strips of cat spleen, a tissue rich in receptors, was measured in response to graded doses of norepinephrine. Left Tolazoline, a reversible blocker, shifted the curve to the right without decreasing the maximum response when present at concentrations of 10 and 20 l mol/L. Right Dibenamine, an analog of phenoxybenzamine and irreversible in its action, reduced the maximum response attainable... 

Inhaled (volatile) anesthetics are delivered to the lungs in gas mixtures in which concentrations and flow rates are easy to measure and control. However, dose-response characteristics of volatile anesthetics are difficult to quantify. Although achievement of an anesthetic state depends on the concentration of the anesthetic in the brain (ie, at the effect site), concentrations in the brain tissue are obviously impossible to measure under clinical conditions. Furthermore, neither the lower nor the upper ends of the graded dose-response curve defining the effect on the central nervous system can be ethically determined because at very low gas concentrations awareness of pain may occur. Moreover, at high concentrations there is a high risk of severe cardiovascular and respiratory depression. Nevertheless, a useful estimate of anesthetic potency can be obtained using quantal dose-response principles for both the inhaled and intravenous anesthetics. 

A graded dose-response curve for a series of agonists can provide which of the following data ... 

In the case of cytotoxic agents for which the mechanism of action is nonspecific, toxicity is the major endpoint in such studies and dose-response curves can be established. First, the dose-limiting toxicity (DLT) must be defined. It may be a single adverse event (AE) or a combination of toxic events such as any irreversible grade >2 AE or grade 4 thrombocytopenia >1 week or neutropenia with WBC < 1000 for >2 weeks or neutropenic fever >1 week. ... 

Graded dose-response curves also provide information about antagonists—drugs that interact with receptors to interfere with their activation by agonists. 

The curative method involves the use of a scorbutigenic diet for ten days. On the eleventh day when weight loss would be expected to begin, groups of animals are placed on graded doses of the test sample and the ascorbic acid, and the biological value of the sample is calculated from the resultant dose response curves (H6). 

Graded dose-response curve A graph of the increasing responses to increasing doses of a drug... 

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