Permissive antagonism

Kenakin, TP. (2005). New concepts in durg discovery Collateral efficacy and permissive antagonism. Nature Rev. Durg Disc. 4 919-927. 

Kenakin T. New concepts in drug discover collateral efficacy and permissive antagonism. Nat Rev Drug Discov 2005 4(ll) 919-927. 

Figure 7.5 Rate recording of the dose-dependent inhibitory effects of apomorphine (pg/kg) on the spontaneous activity of a neuron in the medial prefrontal cortex of the halothane anaesthetised rat and its antagonism by haloperidol (HAL, 0.5mg/kg). Time scale is 50 min intervals. Reproduced by permission from Dailey (1992)...

Components of F-[IV entry and targets for entry inhibition including coreceptor blockers. There are many different stages of viral entry and each of these is specifically susceptible to antagonism by specific compounds. The compounds listed above are in clinical development with the exception of enfuvirtide, which was approved by the Food and Drug Administration (FDA). (Reprinted with permission from Dr. Robert W. Dorns. Available at http //cHnicaloptions.com. Accessed August 25, 2005.)... 

The determination of a permissible exposure to a toxic substance requires evaluation of qualitative and quantitative factors including the identification and health significance of the adverse effect the sensitive members of and the size of the exposed population, biological absorption, distribution, metabolism, and excretion and the possible additivity, synergism, or antagonism with coexposed substances. 

Fig. 12.6 Network level analysis of the proposed editing therapy involving imatinib/WBZ 4 combination treatment. In the CML cells imatinib and WBZ 4 overlap therapeutically by inhibiting common clinically relevant targets PDGFR and KIT, whereas in cardiomyocytes, the inhibitory action of WBZ 4 on JNK antagonizes the pro-apoptotic pathways activated by upstream inhibition of ABL by imatinib. Reprinted from [32], copyright 2009 with permission from Elsevier...

Figure 6. Double reciprocal plot demonstrating antagonism of diphenyhydramine and ergotamine to the blood pressure lowering effects of histamine in the dog. (Reprinted with permission from Ref. 10.)...

Figure 9. Demonstration of competitive antagonism of the of the effect of norepinepherine on the isolated cat spleen preparation by tolazoline. (Reproduced with permission from Ref. 11.)...

Fig. 28.18 Representation of T cell agonism and antagonism. (Reproduced with permission from reference 113.)...

Figure 10 Calcium antagonism of the dihydropyridine lactones (6) plot of the angular deviation Aa vs. KI (reproduced from Figure 6 of ref [349] with permission from the copyright owner).

Fig. 7, Effects of a 1 1 mixture of copper-mercury (— —) on developmental stages of the rainbow trout. The mixture was less toxic than copper (—) at low exposure levels but equally toxic as mercury (—) when the concentration was increased to 0.05 mg/liter. When LCjo values for individual metals were compared, mercury was approximately 25 times more toxic than copper. The curve for calculated additive effects (solid line) served as a basis for assessing antagonism and synergism. [Reprinted with permission from Copper in the Environment (J. O. Nriagu, ed.). Copyright , John Wiley and Sons, Inc., New York.]...

Safety and permissiveness are antagonistic. We take this antagonism into account by designing the monitor to be maximally permissive with respect to safety, i.e., to restrict functionality only to the extent necessary to ensure safety. 

In general, permissible preservatives and their maximum allowed concentrations are related to the specific cosmetic product, because it is also necessary to consider their compatibility with all the ingredients of the often intricate cosmetic formulas, their antagonism or synergism. In this sense, for instance, Bianco-Prevot et al. (2(KX)) deal with the issue giving the example of formulations like shampoos, which consist of a micellar surfactant solution. In such formulations the partition process taking place between the aqueous and the micellar phase could affect the preservative action, because the concentration is lowered in the aqueous fraction, in which bacteria activity is predominant. Therefore, the correlation between antimicrobial activity and micelle/water partitioning of preservatives must be considered. 

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