Antagonisms

Antagonism may be defined as the situation in which the toxicity of two or more compounds present or administered together or sequentially is less than would be expected in terms of their toxicities when administered separately. Antagonism may be due to chemical or physical characteristics of the pollutants, or it may be due to the biological actions of the pollutants involved. For example, the highly toxic metal cadmium (Cd) is known to induce anemia and nephrogenic hypertension as well as teratogenesis in animals. Zinc (Zn) and 

Physical means of antagonism can also exist. For example, oil mists have been shown to decrease the toxic effects of 03, N02, and certain hydrocarbons in experimental mice. This may be due to the oil dissolving the gas and holding it in solution or to the presence of neutralizing antioxidants in the oil. 

Antagonism occurs when two chemicals interfere with each other s effect. The result is a reduction in the effect predicted for the individual species. Antagonistic mixtures need not be structurally similar. One species may stimulate the metabolism of a second one or somehow interfere with its sorption. Antagonism can be considered the antithesis of synergism (discussed later). 

Examples of chemical mixtures that produce antagonisms and their effects are 

DDT and parathion (DDT induces and parathion inhibits enzymatic activity)  

oxygen and carbon monoxide (oxygen competes with CO for receptor sites) [61 and 

toluene and benzene (toluene inhibits benzene metabolism and reduces its toxicity) 

The thermally induced changes may not always be beneficial. Polysaccharide decomposition products are generally considered safe for human consumption, but traces of potentially deleterious compounds, e.g., phenol (Byrne et al., 1966) and acrolein (Walter and Fagerson, 1968), may appear. The 7-lactone of 4-hydroxy-2-pentenoic acid—a vapor-phase constituent of the pyrolysate—has been implicated in antibiosis (Oxford, 1945). 

On occasion, the term synergism has been applied to inhibitor interaction based simply on the observation that inhibition by combined application of A and B exceeds that obtained by either A or B alone. The term synergism is also occasionally used in describing growth promoter interactions in which promotion by A plus B is greater than that obtained by A or B alone. According to accepted definitions, these would not qualify as synergistic interactions. 

When A suppresses a response promoted by B, A and B are said to have opposite effects. Hormone A inhibits the parameter promoted by B. This does 

Hormones acting in any fashion to influence the same parameter 

Hormones influencing the same parameter in an additive fashion (action at different sites) 

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It is a powerful antagonist of histamine, antagonizing its effect on smooth muscle of the bronchioles, bladder and partially the intestines and preventing the dilation of capillaries. Promethazine is used in the treatment of allergic reactions. 

The action of the sulphonamides is antagonized by p-aminobenzoic acid and they act by inhibiting the uptake and utilization of 1-aminobenzoic acid by bacterial cells, which require this as a precursor of folic acid. 

Antagonism between antimony oxide and phosphoms flame retardants has been reported in several polymer systems, and has been explained on the basis of phosphoms interfering with the formation or volatilization of antimony haUdes, perhaps by forming antimony phosphate (12,13). This phenomenon is also not universal, and depends on the relative amounts of antimony and phosphoms. Some useful commercial poly(vinyl chloride) (PVC) formulations have been described for antimony oxide and triaryl phosphates (42). Combinations of antimony oxide, halogen compounds, and phosphates have also been found useful in commercial flexible urethane foams (43). 

E. D. Wed, "Additivity, Synergism and Antagonism in Flame Retardancy - Recent Developments," paper presented at 3rdMnnualBCC Conference on... 

The antagonisms that exist between unsaturated fatty acids, and carotene and vitamin E are compHcated and largely undefined. Linoleic acid acts as an antivitamin to i7/-a-tocopherol [59-02-9, 1406-18-9, 10191-41-0] (vitamin E) by reducing availabiHty through direct intestinal destmction. Various Hpoxidases destroy carotenes and vitamin A (73). Dicoumarol [66-76-2] (3,3 -methylenebis(4-hydroxycoumarin)) is a tme antimetaboHte of vitamin K [12001 -79-5] but seems to occur only in clover and related materials that are used primarily as animal feeds (74). 

Histamine H2 Receptor Antagonists. In 1972 a new class of histamine antagonists was described that was capable of antagonizing histamine-induced gastric acid secretion (6). The H2 antagonists are divided into five stmctural classes, some of which are shown in Table 3. A more complete review can be found in Reference 25. 

The red tetrathiomolybdate ion appears to be a principal participant in the biological Cu—Mo antagonism and is reactive toward other transition-metal ions to produce a wide variety of heteronuclear transition-metal sulfide complexes and clusters (13,14). For example, tetrathiomolybdate serves as a bidentate ligand for Co, forming Co(MoSTetrathiomolybdates and their mixed metal complexes are of interest as catalyst precursors for the hydrotreating of petroleum (qv) (15) and the hydroHquefaction of coal (see Coal conversion processes) (16). The intermediate forms MoOS Mo02S 2> MoO S have also been prepared (17). 

ANPs play an important role in the maintenance of cardiovascular homeostasis by counterbalancing the renin—angiotensin (RAS) system. ANP, the main circulating form of the natriuretic peptides, effectively relaxes vascular smooth muscle, promotes the excretion of sodium and water, and in the CNS inhibits vasopressin release and antagonizes AT-II induced thirst. 

Three classes of OA receptor, OA-1—OA-3, have been described on the basis of antagonist sensitivities and location (71). The OA-1 receptor is antagonized by the adrenoceptor antagonist, phentolamine (87) and the OA-2 receptor is blocked by mianserin [24219-97-4] C gH2QN2 (271). The OA-3 receptor is similar to the OA-2 receptor but is found in nerve cord and insect brain. TMP, C22H2gN2 (272) and NC5Z, (273) are more potent... 

Dynorphin may also influence nociception at the spinal level. The levels of prodynorphin mRNA and immunoreactive dynorphin increase in the chronic inflammatory arthritic model (158). Dynorphin also inhibits morphine or P-endorphin-induced analgesia in naive animals and enhances analgesia in tolerant animals, indicating that this peptide may have a regulatory role in opioid analgesia (159). This effect does not appear to be mediated by a classical opioid receptor, since des-tyrosine dynorphin, which does not bind to opioid receptors, also antagonizes morphine analgesia (160). 

The replacement of the /V-methyl group on the nitrogen atom of the piperidine ring of morphine and analogues by aHyl, isopropyl, or methyl cyclopropyl, an isopropyl isostere, results in compounds which antagonize opioid responses, especially respiratory depression. Naloxone [465-65-6] C22H2 N04 (10... 

Other specific discovery assays have been used such as differential inhibition of a vancomycin resistant S. aureus strain and its susceptible parent, and an assay based on antagonism of the antibacterial activity by N,A/-diacetyl-L-Lys-D-Ala-D-Ala [24570-39-6] a tripeptide analogue of the dalbaheptides receptor. AppHcation of this latter test to 1936 cultures (90) led to the isolation of 42 dalbaheptides, six of which, including kibdelin (Table 3), parvodicin (Table 3), and actinoidin A2 (68) were novel. A colorimetric assay based on competition between horseradish peroxidase bound teicoplanin and the... 

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