Synergistic inhibitors

Organism Insecticide Detoxifying Enzyme Inhibitor (Synergist) Synergistic Ratio... 

One approach to combating antibiotic resistance caused by P-lactamase is to inhibit the enzyme (see Enzyme inhibition). Effective combinations of enzyme inhibitors with P-lactam antibiotics such as penicillins or cephalosporins, result in a synergistic response, lowering the minimal inhibitory concentration (MIC) by a factor of four or more for each component. However, inhibition of P-lactamases alone is not sufficient. Pharmacokinetics, stability, ability to penetrate bacteria, cost, and other factors are also important in determining whether an inhibitor is suitable for therapeutic use. Almost any class of P-lactam is capable of producing P-lactamase inhibitors. Several reviews have been pubUshed on P-lactamase inhibitors, detection, and properties (8—15). 

R = an aromatic moiety, = H, and R" = R" = CH ), which were expected to have a long-hved acyl enzyme species (26) that would react further to give inactivated enzyme. The compounds all act as P-lactamase inhibitors but they are poor synergists. Aged solutions of c1oxaci11in sulfone, where... 

There are in addition several other factors that accelerate corrosion and must betaken into account these include crevices, galvanic coupling, tensile stress, aeration, presence of impurities, surface finish, etc. If these were also taken into consideration then several million experiments would have to be performed to compile such data. There are many instances where two or more chemicals exert a marked synergistic action such that low dissolution rates obtained in either environment become much greater in the presence of both. Further, the corrosiveness of a chemical will be affected by the presence of certain impurities, which may act as either accelerators or inhibitors. To take all these factors into account would add to an already impossible task and as Evans has remarked, There are not enough trained investigators in the world to obtain the empirical information to cover all combinations of conditions likely to arise . Unfortunately corrosion science has not yet reached the stage where prediction, based on a few well established laws, allows selection of materials to be made without recourse to a vast amount of data. 

Thus, effectiveness of basic (alkaline) additives has been greatly improved by increasing their solubility in base stocks, by exploiting synergistic action between two similar additive types and by the use of a third additive to enhance (catalyse) the performance of the other two. Similar principles have been used to augment the performance of oxidation inhibitors. 

N— compounds used as acid inhibitors include heterocyclic bases, such as pyridine, quinoline and various amines. Carassiti describes the inhibitive action of decylamine and quinoline, as well as phenylthiourea and dibenzyl-sulphoxides for the protection of stainless steels in hydrochloric acid pickling. Hudson e/a/. refer to coal tar base fractions for inhibition in sulphuric and hydrochloric acid solutions. Good results are reported with 0-25 vol. Vo of distilled quinoline bases with addition of 0 05m sodium chloride in 4n sulphuric acid at 93°C. The sodium chloride is acting synergistically, e.g. 0-05m NaCl raises the percentage inhibition given by 0-1% quinoline in 2n H2SO4 from 43 to 79%. Similarly, potassium iodide improves the action of phenylthiourea . 

In the case of ions, the repulsive interaction can be altered to an attractive interaction if an ion of opposite charge is simultaneously adsorbed. In a solution containing inhibitive anions and cations the adsorption of both ions may be enhanced and the inhibitive efficiency greatly increased compared to solutions of the individual ions. Thus, synergistic inhibitive effects occur in such mixtures of anionic and cationic inhibitors . These synergistic effects are particularly well defined in solutions containing halide ions, I. Br , Cl", with other inhibitors such as quaternary ammonium cations , alkyl benzene pyridinium cations , and various types of amines . It seems likely that co-ordinate-bond interactions also play some part in these synergistic effects, particularly in the interaction of the halide ions with the metal surfaces and with some amines . 

The four mechanisms discussed above, of the action of inhibitors remain essentially unchanged. Further work on acetylenic alcohols has indicated that barrier films can form owing to crosslinking by hydrogen bonding and synergistic interactions . Theoretical treatments of the electrochemical... 

Apart from nitrite and molybdate, silicate is commonly employed in anodic inhibitor programs, although seldom as the primary inhibitor. Both silicates and molybdates provide benefits of synergistic inhibition and also help to reduce corrosion risks through softer waters and multimetal systems. 

For larger, more complex LPHW systems and for LP steam heating systems, silicates are seldom used alone but are formulated with nitrite or molybdate inhibitors to provide synergistic corrosion protection. 

When Hie cholinesterase inhibitors are administered with the anticholinergic drugp, there is a potential decrease in activity of the anticholinergic drug. There is an increased risk of toxicity of theophylline when the cholinesterase inhibitors are administered with tacrine There is a synergistic effect when tacrine is administered with succinyl-choline, cholinesterase inhibitors, or cholinergic agonists (eg, bethanechol). 

It is important to recognize that different types of inhibitors often function by different mechanisms, and that a given antioxidant may react in more than one way. Thus, a material that acts as an antioxidant under one set of conditions may become a pro-oxidant in another simation. The search for possible synergistic combinations of antioxidants can be conducted more logically and efficiently if we seek to combine the effects of different modes of action. Five general modes of oxidation inhibition are commonly recognized ... 

Ma J, Endres M, Moskowitz MA. Synergistic effects of caspase inhibitors and mk-801 in brain injury after transient focal cerebral ischaemia in mice. Br J Pharmacol 1998 124 756-762. 

Ma J, Qiu J, Hirt L, Dalkara T, Moskowitz MA. Synergistic protective effect of caspase inhibitors and bfgf against brain injury induced by transient focal ischaemia. Br J Pharmacol 2001 133 345-350. 

Quaternary ammonium iodides were tested alone and in combination with propargyl alcohol with several steels in 15% HCl. The quaternary ammonium iodides showed superior inhibitor performance to that of propargyl alcohol (propargyl = —CH2-C=CH) at identical dosage levels. Mixtures of propargyl alcohol and quaternary anunonium iodide showed a synergistic effect [1330], as did formic acid [246] and thiols [1808]. 

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