Potency dose-response curves

From the dose-response curves, potency ratios and confidence limits are calculated. This approach may be modified for short term uptake of 13 I or 1251 as a parameter of thyroid peroxidase inhibition by antithyroid drugs. 

As discussed previously, the location parameter of a dose-response curve (potency) of a full agonist is a complex amalgam of the affinity and efficacy of the agonist for the receptor and the ability of the system to process receptor... 

Dose-response curves quantify drag activity. The maximal asymptote is totally dependent on efficacy, while potency is due to an amalgam of affinity and efficacy. 

When an antagonist produces parallel shifts to the right of the dose-response curve with no diminution of the maximal response, the first approach used to quantify potency is Schild analysis (see Section 6.3.1). In cases where the value of a is low (i.e., a = 0.01), a tenfold concentration range of the antagonist would cause shifts commensurate with those produced by a simple competitive antagonist. 

FIGURE 10.3 Comparative potencies of two agonists in two receptor systems containing the same receptor at different receptor densities, (a) Relative potency in system with high receptor density (x, = 500, x2= 100). The potency ratio = 5. (b) Dose-response curves for same two agonists in receptor system with 1/100 the receptor density. Potency ratio = 1.3. 

General Procedure Dose-response curves are obtained for an agonist in the absence and presence of a range of concentrations of the antagonist. The dextral displacement of these curves (ECSo values) are fit to a hyperbolic equation to yield the potency of the antagonist and the maximal value for the cooperativity constant (a) for the antagonist. 

Log normal distribution, the distribution of a sample that is normal only when plotted on a logarithmic scale. The most prevalent cases in pharmacology refer to drug potencies (agonist and/or antagonist) that are estimated from semilogarithmic dose-response curves. All parametric statistical tests on these must be performed on their logarithmic counterparts, specifically their expression as a value on the p scale (-log values) see Chapter 1.11.2. 

Potency, the concentration (usually molar) of a drug that produces a defined effect. Often, potencies of agonists are defined in terms of EC50 or pECso values. The potency usually does not involve measures of maximal effect but rather only in locations along the concentration axis of dose-response curves. 

Schild analysis, this powerful method of quantifying the potency of a competitive antagonist was developed by Heinz Schild (Br. J. Pharmacol. 14,48-58, 1959 see Chapter 6.3). It is based on the principle that the antagonist-induced dextral displacement of a dose-response curve is due to its potency (K% value) and its concentration in the receptor compartment. Because the antagonism can be observed and the concentration of antagonist is known, the KB can be calculated. 

Free drug concentration description of, 36-37 measurement of, in receptor compartment, 39 Frovatriptan, 163f Full agonism, 200-202 Full agonists affinity of, 261 description of, 27—30 dose-response curves for, 90, 200-202 Furchgott method for affinity measurements, 261 potency ratios for, 202—204, 219—220 Functional assays... 

Fig. 1). If an agonist produces a submaximal system response it is called a partial agonist (Fig. 1). While the potency of an agonist is quantified by the location parameter of the dose-response curve (EC50), a reflection of (but not a direct measure of) the intrinsic efficacy of an agonist is given by its maximal response. 

Qi — The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the multistage procedure. The q, can be used to calculate an estimate of carcinogenic potency, the incremental excess cancer risk per unit of exposure (usually pg/L for water, mg/kg/day for food, and pg/m for air). 

If the behavioral activity of PCP is related to its block of pre-synaptic K channels (Albuquerque et al. 1981 Albuquerque et al. 1983 Blaustein and Ickowicz 1983), PCP-like analogues should block these same K channels with a rank order of potency that parallels their relative in vi vo psychotomimetic activity. One of the most behavioral ly potent PCP-like agents is TCP (1 -[1 -(2 -thienyl)-cyclohexyl] piperidine) (Shannon 1983). Figure 4 illustrates the dose-response curves for the block of components S and T by this drug. The data indicate that TCP is a more potent blocker of Sv than is PCP (figure 2). TCP blocked component T only at high concentrations (>10 5M), and in this respect was approximately equivalent in potency to PCP (figure 2). 

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