Mills, John A
Working in a psychiatrically innovative environment created by the Government of Saskatchewan, Canada, Abram Hoffer and Humphry F. Osmond enunciated the adrenochrome hypothesis for the biogenesis of schizophrenia in 1952, slightly later proposing and, apparently, demonstrating, in a double-blind study, that the symptoms of the illness could be reversed by administering large doses of niacin. After placing the hypothesis within its ideological framework, the author describes its emergence and elaboration and discusses the empirical evidence brought against it. Hoffer's idiosyncratic diagnostic procedures, especially his creation and use of a supposed biochemical marker for schizophrenia, are examined. The author argues that Hoffer's conceptualization of schizophrenia, as well as his treatment approach, depended on a tautology. Following David Healy, the author treats the adrenochrome hypothesis as a version of a transmethylation theory, thus incorporating it into mainstream psychopharmacology.
张占军; 李经建; 吴锡尊; 张文智; 蔡生民
The kinetic characteristics of the electrochemical oxidation of Adrenaline to adrenochrome was studied by UV-Vis Spectroscopy.The measurements showed that the electrooxidation of adrenaline to adrenochrome was typical of the first order reaction and the average apparent rate constant is 1.921×10-4s-1.%以紫外-可见分光光度法为主要手段，研究了肾上腺素电氧化生成肾上腺素红的反应动力学特征。研究结果表明：该反应具有一级反应的动力学特征，且反应的表观反应速率常数的平均值为1.921×10-4s-1。
Fu, Yue; Buryanovskyy, Leonid; Zhang, Zhongtao (NYMEDCO)
The functions of quinone reductase 2 have eluded researchers for decades even though a genetic polymorphism is associated with various neurological disorders. Employing enzymatic studies using adrenochrome as a substrate, we show that quinone reductase 2 is specific for the reduction of adrenochrome, whereas quinone reductase 1 shows no activity. We also solved the crystal structure of quinone reductase 2 in complexes with dopamine and adrenochrome, two compounds that are structurally related to catecholamine quinones. Detailed structural analyses delineate the mechanism of quinone reductase 2 specificity toward catechol quinones in comparison with quinone reductase 1; a side-chain rotational difference between quinone reductase 1 and quinone reductase 2 of a single residue, phenylalanine 106, determines the specificity of enzymatic activities. These results infer functional differences between two homologous enzymes and indicate that quinone reductase 2 could play important roles in the regulation of catecholamine oxidation processes that may be involved in the etiology of Parkinson disease.
Sirota, T V
An important role of carbonate/bicarbonate ions has been recognized in the superoxide generating reaction of adrenaline autooxidation in an alkaline buffer (a model of quinoid adrenaline oxidation in the body). It is suggested that these ions are directly involved not only in formation of superoxide anion radical (О(2)(-)) but also other radicals derived from the carbonate/bicarbonate buffer. Using various buffers it was shown that the rate of accumulation of adrenochrome, the end product of adrenaline oxidation, and the rate of О(2)(-)· formation depend on concentration of carbonate/bicarbonate ions in the buffer and that these ions significantly accelerate adrenaline autooxidation thus demonstrating prooxidant properties. The detectable amount of diformazan, the product of nitro blue tetrazolium (NBT) reduction, was significantly higher than the amount of adrenochrome formed; taking into consideration the literature data on О(2)(-)· detection by NBT it is suggested that adrenaline autooxidation is accompanied by one-electron reduction not only of oxygen dissolved in the buffer and responsible for superoxide formation but possible carbon dioxide also dissolved in the buffer as well as carbonate/bicarbonate buffer components leading to formation of corresponding radicals. The plots of the dependence of the inhibition of adrenochrome and diformazan formation on the superoxide dismutase concentration have shown that not only superoxide radicals are formed during adrenaline autooxidation. Since carbonate/bicarbonate ions are known to be universally present in the living nature, their involvement in free radical processes proceeding in the organism is discussed.
Sirota, T V
The superoxide-generating reaction of adrenaline autoxidation is widely used for determination of the activity of superoxide dismutase and pro/antioxidant properties of various materials. There are two variants of the spectrophotometric registration of the products of this reaction. The first is based on registration of adrenochrome, as adrenaline autooxidation product at 347 nm; the second employs nitro blue tetrazolium (NBT) and registration of diformazan, a product of NBT reduction at 560 nm. In the present work, recommendations for the standardization of the reaction rate in both variants have been proposed. The main approach consists in the use of the pharmaceutical form of 0.1% adrenaline hydrochloride solution. Although each of two adrenaline preparations available in the Russian market has some features in kinetic behavior of its autooxidation; they are applicable in the superoxide generating system based on adrenaline autooxidation. Performing measurements at 560 nm, the reaction rate can be regulated by lowering the concentration of added adrenaline, whereas during spectrophotometric registration at 347 nm, this cannot be done. These features of adrenaline autoxidation may be due to the fact that the intrinsic multistage process of the conversion of adrenaline to adrenochrome, which is recorded at 347 nm, is coupled with the transition of electrons from adrenaline and intermediate products of its oxidation to oxygen, carbon dioxide, and carbonate bicarbonate ions, which is detected in the presence of added NBT.
李萍; 张福田; 刘刚; 周磊; 吴守国
建立了系统测定利多卡因肾上腺素注射液中肾上腺素、去甲肾上腺素、亚硫酸肾上腺素及肾上腺素红含量的高效液相色谱-电化学(HPLC-ECD)方法.其中前3种物质用氧化模式分析,肾上腺素红用还原模式分析.优化了电位、流动相pH及离子对试剂含量、灵敏度参数等色谱条件,并对该方法进行了论证:在各物质的线性浓度范围内,该方法显示出良好的线性关系,R2均为0.9999,肾上腺素、去甲肾上腺素、亚硫酸肾上腺素和肾上腺素红的检出限依次为0.27,0.50,0.20,50 μg·L-1,回收率依次为(100.34±0.62)％,(100.16±1.07)％,(100.26±1.21)％,(97.97±0.72)％ (n=9).该方法快速简单、选择性好、灵敏度及准确度高,可用于肾上腺素及其相关物质的分析测定.%An reverse phase high performance liquid chromatography (RP-HPLC) assay coupled with electrochemical detection (ECD) for systematically measuring epinephrine, norepinephrine, epinephrine sulfonate and adrenochrome in lidocaine epinephrine injection was developed. Analyses of epinephrine, norepinephrine and epinephrine sulfonate were conducted in oxidation mode, while adrenochrome was analysed in reduction mode. Chromatographic conditions such as potential, pH and ion-pair reagent content of mobile phase and sensitivity range were optimized. The proposed method was demonstrated strictly. The method shows good linear relationship (R2 = 0. 999 9) in the linear concentration range of four analytes. The detection limit of epinephrine, norepinephrine, epinephrine sulfonate and adrenochrome is 0.27, 0.50, 0.20, 50 μg · L-1, respectively, and the recovery of these substances is (100.34 ± 0.62)%, (100.16±1.07)%, (100.26 ± 1.21)%, (97.97±0.72)% (n=9), respectively. The method is fast and simple and showed high sensitivity, precision, selectivity and recovery, and can thus be used as a quality control method for drugs containing epinephrine and related substances.
Lombardo Lupano, Lucía Victoria; Lázaro Martínez, Juan Manuel; Piehl, Lidia Leonor; Rubín de Celis, Emilio; Torres Sánchez, Rosa María; Campo Dall' Orto, Viviana
Here, we report the synthesis and characterization of a hydrogel based on ethylene glycol diglycidyl ether (EGDE) and 1,8-diamino-3,6-dioxaoctane (DA). Chemically stable Co(II) and Cu(II) coordination complexes were prepared with this nonsoluble polyelectrolyte, poly(EGDE-DA), and studied by ss-NMR, FT-IR, thermogravimetry, and microscopy. Mesopores were found in all the samples, the thermal stability of the polymer matrix was highly affected by the presence of metal ions, and the (13)C CP-MAS spectrum for the Cu(II)-complex evidenced a significant increase in the reticulation degree by Cu(II) ions. The catalytic activity of these materials on H2O2 activation was studied by electron spin resonance (ESR). The Co(II)-poly(EGDE-DA)/H2O2 heterogeneous system produced O2, an anion superoxide (O2(•)¯), and a hydroxyl radical (OH(•)), which diffused into the solution at the time that a decrease in pH was detected. In the same way, the Cu(II)-poly(EGDE-DA)/H2O2 heterogeneous system produced O2 and OH(•). H2O2 activation by the poly(EGDE-DA) complexes with Co(II) and Cu(II) were applied on the decolorization of solutions of the azo-dye methyl orange (MO). In the presence of 63 mM H2O2, 87% of MO was removed in 10 min with Cu(II)-poly(EGDE-DA) and in 110 min with Co(II)-poly(EGDE-DA). In addition, the pharmaceutical product epinephrine was partially oxidized to adrenochrome by the O2(•)¯ released from the Co(II)-poly(EGDE-DA)/H2O2 heterogeneous system.
Roginsky, V A; Bruchelt, G; Bartuli, O
The kinetics of ascorbate (AscH ) and epinephrine (EP) oxidation in the presence of 2,3-dimethoxy-5-methyl-1,4-benzoquinone (UQ) were studied in 0.05 M phosphate buffer, pH 7.4, at 37 degrees C by using a Clark electrode and ESR techniques. UQ at nanomolar concentrations displayed a pronounced catalytic effect on AscH oxidation which exceeded that of all reported organic catalysts tested in this system. The process was accompanied by the intensive oxygen consumption and increase in the steady-state concentration of the ascorbyl radical Asc.-. The rate of oxygen consumption (R[OX]) was maximal at the moment of reagent mixing ((R[OX]0) and then reduced over a few minutes until a steady-state level ((R[OX])SS) was achieved. (R[OX])0 was found to be proportional to [UQ][AscH-] without regard to the concentrations of the individual reagents; (R[OX])SS was directly related to [UQ] at a given concentration of AscH-. The difference between (R[OX])0 and (R[OX])SS decreased as [AscH-] decreased. The presence of a lipid phase (sodium dodecylsulphate micelles) only moderately decreased UQ activity as a catalyst of AscH- oxidation. Adding micromolar concentrations of UQ induced the acceleration of EP autoxidation. The capability of UQ to catalyze the oxidation of EP exceeded by approximately 25 times that of adrenochrome, a quinoid product of EP oxidation. These catalytic properties of UQ allowed us to predict its pronounced cytotoxicity, especially in the presence of AscH- and to cells of the sympathetic nervous system which are rich in catecholamines. This possibility was confirmed by experiments with human neuroblastoma cells in culture. The capability of UQ to injure neuroblastoma cell line SK-N-SH exceeded that of well-known neurotoxic agents 6-hydroxydopamine and menadione.