Activity intrinsic

The term intrinsic activity (ia) was defined as a measure of the abiUty of the dmg—receptor complex to generate response. When ia = 1, a full agonist is defined when ia = 0, an antagonist is defined. Thus, values 0 < ia < 1 define partial agonists as follows, where R is the response to dmg and R is the maximum response achieved. 

The sulfated compounds MM 13902 (3, n = (5) and MM 17880 (4) are also broad-spectmm agents, but not as potent as thienamycia and all lack any significant activity against Pseudomonas (73). Many carbapenems are excellent inhibitors of isolated P-lactamases, particularly the olivanic acid sulfoxide MM 4550 (3, n = 1) (3). The possible mechanism of action of the carbapenems as inhibitors of P-lactamases has been discussed in some detail (74). Other carbapenems such as PS-5 (5) (75), the carpetimycins (76), asparenomycins (77), and pluracidomycins (8) are all highly active as antibiotics or P-lactamase inhibitors. The parent nucleus itself (1, X = CH2) is intrinsically active, but chemically unstable (9). 

Although the activity of methoxylated monobactams could be improved by appropriate side-chain modifications, difficulty of synthesis and poor chemical stabihty focused attention on the nonmethoxylated analogues. Both high intrinsic activity and excellent P-lactamase stabiUty are exhibited by monobactams that combine C-3 arninothia2ole oxime side chains and 4-alkyl, 4-alkenyl, and 4-alkynyl groups (19). 

The biological activity of SQ 28,112 (43), shown in Table 4, is typical of the monophosphatams which possess the same spectmm of activity as a2treonam, but have comparatively lower intrinsic activity and P-lactamase stabiUty. 

The hydroformylation reaction is carried out in the Hquid phase using a metal carbonyl catalyst such as HCo(CO)4 (36), HCo(CO)2[P( -C4H2)] (37), or HRh(CO)2[P(CgH3)2]2 (38,39). The phosphine-substituted rhodium compound is the catalyst of choice for new commercial plants that can operate at 353—383 K and 0.7—2 MPa (7—20 atm) (39). The differences among the catalysts are found in their intrinsic activity, their selectivity to straight-chain product, their abiHty to isomerize the olefin feedstock and hydrogenate the product aldehyde to alcohol, and the ease with which they are separated from the reaction medium (36). 

Figure 10 shows that Tj is a unique function of the Thiele modulus. When the modulus ( ) is small (- SdSl), the effectiveness factor is unity, which means that there is no effect of mass transport on the rate of the catalytic reaction. When ( ) is greater than about 1, the effectiveness factor is less than unity and the reaction rate is influenced by mass transport in the pores. When the modulus is large (- 10), the effectiveness factor is inversely proportional to the modulus, and the reaction rate (eq. 19) is proportional to k ( ), which, from the definition of ( ), implies that the rate and the observed reaction rate constant are proportional to (1 /R)(f9This result shows that both the rate constant, ie, a measure of the intrinsic activity of the catalyst, and the effective diffusion coefficient, ie, a measure of the resistance to transport of the reactant offered by the pore stmcture, influence the rate. It is not appropriate to say that the reaction is diffusion controlled it depends on both the diffusion and the chemical kinetics. In contrast, as shown by equation 3, a reaction in solution can be diffusion controlled, depending on D but not on k. 

The precious metal or metal oxide imparts high intrinsic activity, the carrier provides a stable, high surface area for catalyst dispersion, and the mechanical support gives a high geometric surface area for physical support and engineering design features (20). Only the correct combination of these... 

The anticonvulsant primidone (1035) resembles phenobarbital but lacks the 2-oxo substituent. It was introduced in 1952 and has remained a valuable drug for controlling grand mal and psychomotor epilepsy. As might be expected, primidone is metabolized to yield phenobarbital (1034 X = 0) and C-ethyl-C-phenylmalondiamide (1036), both of which have marked anticonvulsant properties however, primidone does have intrinsic activity and an appropriate mixture of its metabolites has only a fraction of its activity (73MI21303). Primidone may be made in several ways, of which desulfurization by Raney nickel of the 2-thiobarbiturate (1034 X = S) or treatment of the diamide (1036) with formic acid (at 190 °C) seem to be the most satisfactory (54JCS3263). 

Let us define the activation energy for a (possible hypothetical) thermoneutral reaction as the intrinsic activation energy, AEq. As seen from eq. (15.10), a = 4A q. The TS position and activation energy now become... 

The latter is, except for a couple of terms related to solvent reorganization, the Marcus equation. The central idea is that the activation energy can be decomposed into a component characteristic of the reaction type, the intrinsic activation energy, and a correction due to the reaction energy being different from zero. Similar reactions should have similar intrinsic activation energies, and the Marcus equation obeys both the BEP... 

The effectiveness of antioxidants depends not only on their intrinsic activity but also on their physical retention in the polymer. Migration of antioxidants into the sur-... 

FIGURE 3.7 Principal components of the operational model. The 3D array defines processes of receptor occupation (plane 1), the transduction of the agonist occupancy into response (plane 2) in defining the relationship between agonist concentration, and tissue response (plane 3). The term a refers to the intrinsic activity of the agonist. 

Costa, T., and Herz, A. (1989). Antagonists with negative intrinsic activity at 6-opioid receptors coupled to GTP-binding proteins. Proc. Natl. Acad. Sci. U.S.A. 86 7321-7325. 

Ariens, E. J. (1954). Affinity and intrinsic activity in the theory of competitive inhibition. Arch. Int. Pharmacodyn. Ther. 99 32—49. 

FIGURE 4.19 Correlation of the GTP shift for P-adrenoceptor agonists in turkey erythocytes (ordinates) and intrinsic activity of the agonists in functional studies (abscissae). Data redrawn from [16]. 

Relative intrinsic activity, this actually is redundant, as intrinsic activity itself is defined only in relative terms, i.e., the maximal response of an agonist as a fraction of the maximal response to another agonist. 

Intercellular adhesion molecule-1, 128 Interfacial inhibition, 159 Intrinsic activity, 44-46 Intrinsic efficacy, 9, 45, 115 Inverse agonism, 49, 108 Inverse agonists... 

In the luminescence systems that require a peroxide or an active oxygen species in addition to molecular oxygen (the scaleworm, the tube worm Chaetopterus, the clam Pholas, the squid Symplecto-teuthis), their in vitro luminescence reactions reported are much slower and inefficient compared to their bright in vivo luminescence. The true, intrinsic activation factor in their in vivo luminescence should be determined, and the detailed mechanisms of oxidation should be elucidated. 

Ligands that bind to the receptor, but do not exert a maximal cellular reaction when applied at saturating concentrations are referred to as partial agonists. Their remaining activity is termed intrinsic activity ranging between 0% and 100%. 

The combined intrinsic activities of different efflux pumps play a major role for the intrinsic resistance of Gram-negative bacteria to macrolides and oxazolidi-nones as well as to the intrinsic resistance of Pseudomonas aeruginosa against a broad range of disinfectants and antibiotics. 

This term indicates a receptor ligand having different intrinsic activities at different transduction pathways coupled to a single receptor. To quote Urban et al. (2006 JPET, 104463 PiP) and Kenakin (2007 Trends Pharmacol Sci 28 359-361) the term biased agonism can be considered as a synonym of collateral efficacy, ... 

Although blood pressure control follows Ohm s law and seems to be simple, it underlies a complex circuit of interrelated systems. Hence, numerous physiologic systems that have pleiotropic effects and interact in complex fashion have been found to modulate blood pressure. Because of their number and complexity it is beyond the scope of the current account to cover all mechanisms and feedback circuits involved in blood pressure control. Rather, an overview of the clinically most relevant ones is presented. These systems include the heart, the blood vessels, the extracellular volume, the kidneys, the nervous system, a variety of humoral factors, and molecular events at the cellular level. They are intertwined to maintain adequate tissue perfusion and nutrition. Normal blood pressure control can be related to cardiac output and the total peripheral resistance. The stroke volume and the heart rate determine cardiac output. Each cycle of cardiac contraction propels a bolus of about 70 ml blood into the systemic arterial system. As one example of the interaction of these multiple systems, the stroke volume is dependent in part on intravascular volume regulated by the kidneys as well as on myocardial contractility. The latter is, in turn, a complex function involving sympathetic and parasympathetic control of heart rate intrinsic activity of the cardiac conduction system complex membrane transport and cellular events requiring influx of calcium, which lead to myocardial fibre shortening and relaxation and affects the humoral substances (e.g., catecholamines) in stimulation heart rate and myocardial fibre tension. 

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