Dopamine model generation

In the case of schizophrenia it is dopamine, another neuromodulator not apparently involved in dream generation, whose overactivity results in psychosis and whose blockade by neuroleptics effects antipsychosis. We do not yet see how to fit dopamine and schizophrenic psychosis into the universal model, but hints as to how that might occur are already on the horizon. As the link between motor control and thought becomes better appreciated and the interaction of serotonin, norepinephrine, and dopamine is better understood, we will see, I predict, a seamless continuity among these control systems and their effects on consciousness. 

Now the whole trick of this procedure is the following. Prior to PCA, artificial compounds (or a real set of reference compounds) are added to the data matrix X. These additional data points (library spikes ) have coordinates that represent idealized properties of the library. For example, if the aim is to generate a library for the cannabinoid receptor family, possible coordinates of the idealized artificial compound might be 1 for drug-likeness, 1 for GPCR-ligand-likeness, 1 for cannabinoid-likeness, 0 for dopamine-likeness, 0 for kinase-inhibitor-likeness, and so forth. In this example, the value T indicates the maximum value of a property (presence of a feature), 0 indicates minimum values (absence of a feature). Of course, appropriate prediction models must be at hand. 

Figure 8. Model of the dopamine receptor, with the (- -)-isobutactamol molecule superimposed, generated by the MMS-X computer-based molecular modeling and graphic display system. (Courtesy of Dr. G. Marshall, Washington University, St. Louis).

Fig 24.23. A model for the role of ROS and RNOS in neuronal degradation in Parkinson s disease. 1. Dopamine levels are reduced by monoamine oxidase, which generates H2O2. 2. Superoxide also can be produced by mitochondria, which SOD will convert to H2O2. Iron levels increase, which allows the Fenton reaction to proceed, generating hydroxyl radicals. 3. NO, produced by inducible nitric oxide synthase, reacts with superoxide to form RNOS. 4. The RNOS and hydroxyl radical lead to radical chain reactions that result in Upid peroxidation, protein oxidation, the formation of lipofuscin, and neuronal degeneration. The end result is a reduced production and release of dopamine, which leads to the clinical symptoms observed. 

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