Adrenaline under physiological conditions

Stopped-flow measurements with superoxide in aqueous solution at physiological pH are not possible due to its fast self-dismutation under these conditions. Therefore, the indirect assays such as McCord-Fridovich, adrenalin and nitroblue tetrazolium (NET) assays are widely used in the literature, not only for qualitative but also for quantitative detection of SOD activity of small molecular weight mimetics 52). Not going into details, we just want to stress that the indirect assays have very poor even qualitative reliability, since they can demonstrate the SOD activity of the complexes which does not react with superoxide at all. It has been reported in the literature that this is caused by the interference of hydrogen peroxide 29). We have observed that the direct reaction between complexes and indicator... 

Adrenaline and noradrenaline are unstable in aqueous solution where they are subjected to spontaneous oxidation. In vivo this mechanism is only relevant under pathophysiological conditions of an catecholamine excess, since two enzymes, the catechol-O-methyltransferase (COMT) and the monoamineoxidase (MAO), inactivate physiological amounts of the transmitters. There are at least two subtypes of the enzyme MAO, A and B, which can be inhibited selectively for therapeutic purposes, for example by moclobemide and selegiline. 

Although no free epinephrine is excreted under the conditions of those experiments just described, it is permissible to question whether they are representative of the fate of epinephrine as it is secreted in the body, or whether conjugation is a mode of inactivation of catechol pressor amines administered as drugs. The relatively minute amounts of adrenaline or noradrenaline secreted normally and the limitations of present analytical methods definitely handicap a direct approach to the problem. However, it has been possible to study the fate of adrenaline secreted by the body in a more or less physiological type of experiment. 

Pharmacological Investigations - Pitts and McClure reported that patients with anxiety neurosis show increased levels of lactate in the blood when under conditions of physiological stress or physical exercise. Infusion of lactate in susceptible patients in a double blind study initiated anxiety symptoms. A proposal that over-production of adrenalin by these patients is the cause for increase of lactate was supported by reports that the P-blocker, propranolol, can reduce or eliminate anxiety symptoms. Grosz and Parmer in a critical evaluation of Pitts and McClure s work, feel that these auUors... 

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