Dose Response Relationship

A simple rule of pharmacodynamics is that the size of the effect an agonist (or inverse agonist) elicits is dependent upon the dose of the drug (or, more precisely, its concentration at receptors). When the size of the effect is plotted against the dose, one can notice that the increase in the effect slows down and finally stops when the maximal obtainable response has been achieved (Fig. A.3). It is assumed that the occupancy of receptors and the effect size are proportional, and hence the maximal effect corresponds to the situation when all receptors are already occupied. (However, in many real situations, the maximal effect occurs when many receptors remain unoccupied. Such receptors are referred to as "spare receptors" or "receptor reserve.") Dose-response curves are frequently drawn on a semilogarithmic scale, as in Fig. A.3. Thus, a drug has a dose range in which its concentration logarithm and the size of the effect are linearly proportional, and within this range the predictions made about the dose-effect relationship are most reliable.

In behavioral pharmacology, when drugs are given systemically, we frequently obtain a less clear picture regarding dose dependency. For example, selective serotonin reuptake inhibitors show limited dose dependency in their clinical efficacy, and many antagonists of neuropeptide receptors produce inverted U-shape dose-response curves in animal experiments. The reasons are not always clear, but a biological psychiatrist must bear in mind that after systemic administration, a drug has multiple targets in different brain regions, and thus divergent actions can interfere with each other and shape the dose-response curve.

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Figure A.3. Dose dependency of the effect of four different drugs. This experiment characterized the activation of D2 dopamine receptor-coupled G proteins, as measured by the acceleration of [35S]GTPyS binding to membranes of CHO cells. Receptors were activated by different concentrations of apomorphine (V), quinpirole (O), 5-methoxytryptamine (*), and 8-OH-DPAT (A). On abscissa, concentration of competing substances added to the assay. On ordinate, percent of maximal effect. (Courtesy of Dr. Ago Rinken, Department of Organic and Bioorganic Chemistry, Tartu University.)

Anxiety and Depression 101

Anxiety and Depression 101

Everything you ever wanted to know about. We have been discussing depression and anxiety and how different information that is out on the market only seems to target one particular cure for these two common conditions that seem to walk hand in hand.

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