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The neurotransmitter dopamine (DA) is implicated in the pathophysiology of central nervous system (CNS) illnesses including Parkinson's disease, attention deficit disorder, schizophrenia, and substance abuse. A better understanding of CNS DA function would be of importance in improving our understanding of these conditions. Several lines of evidence suggest that exploring visual system function may be a useful paradigm for examining DA function. Clinical and basic science findings suggest that the visual response to blue light might prove a useful assay of CNS DA tone. To test this hypothesis, we used the functional magnetic resonance imaging (fMRI) BOLD method to measure visual cortical activation in human subjects (N = 6) in response to 8 Hz flashing red and blue light stimuli during placebo conditions and during the oral administration of 2.5 mg of D-amphetamine, a drug known to increase synaptic concentrations of DA and other monoamine neurotransmitters. There was no effect of D-amphetamine administration on the percent BOLD signal change to red or blue light. However, there was a specific augmentation of the spatial extent of activation (as measured by the number of activated pixels; P = 0.018) to blue, but not red light following D-amphetamine administration. This finding is consistent with our hypothesis that blue light function may have utility as an assay of CNS DA tone. However, several limitations to the study, including the small sample size, low dosage of D-amphetamine, and the fact that D-amphetamine increases synaptic concentrations of DA and other monoamine neurotransmitters do not permit a conclusion regarding a specific role for DA in the observed increase in spatial activation to blue light in the amphetamine condition.

The purpose of this study was to assess the impact of impurities in formulation components, antioxidants, formulation pH, and processing/packaging on the extent of color change associated with oxidation of danofloxacin injectable. The methods used in this study include reversed-phase HPLC, UV-VIS spectrophotometry, atomic absorption spectroscopy, visual observation, and iodimetric titration for quantification of the antioxidant. The results from this study revealed that trace impurities from two different excipients significantly contributed to color change associated with oxidation. Polyvinyl pyrrolidone (PVP) introduced trace levels of peroxides into the solution. A second excipient also had a significant impact on stability because it introduced trace metal impurities into the product. The minimization of oxygen levels alone in the solution and headspace was not sufficient to completely eliminate the product instability. The addition of an antioxidant, monothioglycerol (MTG), resulted in a formulation less sensitive to processing variables. The impact of pH on the performance of MTG was also studied. At pH 7.5, MTG resulted in significant improvement in stability; however, at pH 6.0 it was not effective as an antioxidant. Process modifications alone may not be sufficient to prevent oxidation. Chemical approaches, such as pH control, addition of an antioxidant, and control of components should be considered first as means of enhancing stability of oxygen-sensitive solutions.

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