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Microdialysis techniques have been used to measure changes in drug levels and endogenous chemicals in situ. Small hollow plastic tubes are placed stereotaxically into specific parts of a tissue, particularly the brain, and low volumes of buffer are pumped through the system and wash out the chemicals to be analyzed using a flow-through HPLC, linked, if necessary, to a mass spectrometer. Once the animals have been acclimatized to the surgical procedure, this method has the advantage of measuring real-time changes of both drug and hormone or transmitter in close proximity to the site of action. However, although the probes are small, there is still local damage that may affect the results. Also, this technique can only examine a specific part of the brain and other areas that may be involved in controlling the system will be ignored [83]. However, the results are encouraging and have clarified the neuropharmacological action of drugs in terms of the turnover of neurotransmitters reflecting dynamic changes rather than the measurement of gross tissue levels. |
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The newest techniques of nuclear medical imaging are for the first time bringing together all aspects of kinetic-dynamic modeling. These include (a) nuclear magnetic resonance (NMR), (b) positron emission tomography (PET), and (c) single photon emission tomography (SPECT). This chapter is not intended to discuss these methods in detail but instead to provide a brief overview and to show how they can be used in kinetics. |
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The NMR technique has been available for more than 20 years and exploits the magnetic properties of certain atomic nuclei, which, because they have an odd number of protons and or neutrons, will produce a small electromagnetic field [84]. The resonance frequency of a given atom in a magnetic field is fixed and can be measured by stimulating the atoms with radio waves and measuring the transmitted radio frequencies. The instrument determines amount of atom and its position within the body. Major atoms most commonly used are hydrogen to measure water and fluorine-19, but also include nitrogen-14, sodium-13, and potassium-19 [85,86]. This method has high resolution (1 mm) and can provide fine detail of the internal structure of the body, particularly in the brain. It can also measure energy and, therefore, metabolic changes using the phosphorus-31 associated with phosphocreatine and ATP and levels of creatinine, neutral amino acids, lactate, etc. These are very useful to assess loss of organ function, such as in a brain with Alzheimer's or Parkinson's disease. However, its use to measure drug levels is limited since there needs to be some specificity and, although hydrogen and nitrogen are present in many drugs, the levels of endogenous chemical would swamp the signal. But with fluorinated |
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