Potency of drugs

PCMP was equipotent with (+)PCMP in induction of ataxia (figure 2), Furthermore, TCM, which was one-fifth as potent as PCP in the induction of stereotyped behavior, was as potent as PCP in induction of ataxia. The ability of PCP-like drugs to bind to PCP receptors, as measured by their ability to inhibit the binding of 3H- PC P, was determined as described by Contreras et al. (in preparation). The order of relative potencies of drugs as compared to PCP was TCP > PCE > PCP = NIPCA > dexoxadrol > (+) PCMP > TCM =... 

TABLE 1. Relative potency of drugs for inhibition of binding of 3H-PCP, n-(+)SKF-10,047 and 3H-dexoxadrol... 

Unlike mass transport across membranes, which relates to chemical structure in predictable ways, the potencies of drugs as seen in pharmacological, pharmacodynamic, or other tests are highly structurally specific within a class of drugs and are without commonality across classes. A drug s activity involves a complex merging of these separate structural influences, with bioavailability always one of the concerns. Such concern is minimal when a truly superficial effect is involved, however. For example, the most potent antiseptic as measured in the test tube is likely to have... 

Gryglewski RJ, Korbut R, Ocetkiewicz A, Stachura J (1978) In vivo method for quantitation of anti-platelet potency of drugs. Naunyn-Schmiedeberg s Arch Pharmacol 302 25-30... 

With more than 500 members, the proteases constitute one of the largest families of enzymes in the human genome and are an important class of targets for drug discovery. Biochemical assays based on fluorescence readouts are the most frequently used technologies to elaborate the enzymatic mechanisms of proteases and to test the inhibitory potencies of drug-like chemical compounds. These assay formats exist for all classes of proteases and substrate specificities. 

Potency of drug candidates is typically assessed in vitro. An appropriate potency assay must be biologically relevant to the clinical indication for which the drug is targeted. For example, the potency of a growth factor whose action is believed to induce proliferation of epithelial cells in vivo would need to be assessed by an in vitro epithelial cell-based proliferation assay. 

Early in this century, Meyer (109) and Overton (110) showed that the relative potencies of drugs that affect the nervous system correlated with their oil/water partition coefficients. Fifty years later it was shown that partition coefficients in different solvent systems were correlated (111), thus establishing the basis for an extrathermodynamical treatment of partition coefficients. 

Presently, relatively little is known about the potency of drugs of abuse after inhalation or smoking. In order to deter-mine the relationship between volatility and pharmacological potency by the inhalation route, the authors developed an animal model to approximate the conditions of human inhalation. The approach involved a volatilization-inhalation drug delivery system developed over the past 10 years in this laboratory. The design of this inhalation apparatus is illustrated in figure 2. 

TABLE 2. Relative potencies of drugs by inhalation exposure and IV administration. 

These inhalation studies demonstrate the feasibility of evaluating the potency of drugs with different pharmacological actions following inhalation exposure. The comparison of pharmacological effects after both inhalation and IV administration revealed very similar dose-response relationships for each of these three drugs. However, valid potency comparisons can be made between inhalation and IV administration only... 

Since most drugs are chromophoric (exhibit UV absorbances), HPLC with UV detection is commonly used in assays for drug potency of drug substances and products. Typical method attributes, requirements, specification limits, and acceptance criteria are listed Tables 6.2 and 6.3. Assay methodologies of many common drug substances and products are published in the United States Pharmacopeia (USP) or European Pharmacopeia (EP) monographs. Assays for potency are performed for product release and stability evaluation. 

All the compounds studied produced an increase in the amount of ambulation in the open field. Reference to Fig. 2 reveals that the potency of drugs in this respect was not correlated with their potency in increasing spontaneous activity in photocell cages, i.e., it would appear that this increase in open-field ambulation is not precisely analogous to a simple increase in spontaneous activity but that the stress of the open-field situation is modifying this response to the drug. Anderson (1938) reported a similar lack of correlation. 

Table 5-6. Relative Potencies of Drugs in Reducing Stereospecific 3H-Naloxone Binding to Rat Brain Homogenate...

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