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Neuroimaging in Nuclear Medicine
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Anne Larsson Strömvall, Susanna Jakobson Mo
Like a key in a keyhole locking up a door, a neurotransmitter fits into special receptors, which in the receiving neuron triggers a specific process leading to action, a nerve impulse. There may be different kinds of receptors for each kind of neurotransmitter. Dopamine, for example, fits several kinds of dopamine receptors, called the D1, D2, D3, D4, and D5 receptors. The strength of the signal that is transmitted between two neurons depends on the amount of neurotransmitter in the synapse and the amount of time the neurotransmitter is allowed to act on the receptors. Therefore, there are specialized proteins or enzymes that degrade or recycle the released neurotransmitter in order to tune the signal. For example, neurotransmitters called monoamines (dopamine, serotonin, and noradrenaline) have their own transporter proteins (monoamine transporter proteins, MAPs) located at the nerve terminals. These reabsorb the neurotransmitter back into the nerve terminal. In this way, MAPs regulate the amount of available neurotransmitter in the synapse and thereby the response is tuned. In addition, some of the released neurotransmitter is recycled and may be re-used the next time. The dopamine transporter (DAT) is a well-known transporter protein, exclusively found on dopamine producing neurons. Apart from the MAPs, monoaminergic neurotransmission is regulated by enzymes called monoamine oxidase (MAO). The MAOs reduce the amount of available monoaminergic neurotransmitters in the synaptic cleft by decomposition.
The Neurodegenerative Characteristics of Alzheimer’s Disease and Related Multi-Target Drug Design Studies
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Hayrettin Ozan Gülcan, Ilkay Erdogan Orhan
Monoamine oxidase (MAO) enzyme activity is one of the critical steps in the control of the function of several neurotransmitters (e.g., serotonin, dopamine, and norepinephrine). In other words, through the formation of aldehyde derivatives of neurotransmitters via MAO catalyzed oxidative deamination reactions, the amine neurotransmitters are deactivated (Shih et al., 1999). There are two types of MAO enzymes in human, as referred to as MAO-A and MAO-B. They display different tissue distribution and ratios depending on age. Although they are capable of employing a diverse amine substrates, there is some selectivity difference. MAO-A shows selectivity for serotonin, melatonin, norepinephrine, and epinephrine, while MAO-B possesses substrate selectivity for benzylamine and phenethylamine. On the other hand, both enzymes display similar characteristics to catalyze dopamine, tyramine, and tryptamine oxidative deamination reactions (Kalgutkar et al., 2001). Depending on the substrate specificity difference, MAO-A inhibition is mainly preferred as an option in the treatment of some form depression (e.g., to increase the available levels of serotonin, norepinephrine, and dopamine) (Meyer et al., 2006). Parkinson disease–related symptoms are generally related to deficiency of dopamine. Regarding the side effects of MAO-A inhibitors, MAO-B inhibitors (e.g., rasagiline, selegiline) are preferred to increase the available amount of dopamine in CNS (Youdim, 2006).
Drugs for Treatment of Neurological and Psychological Conditions
Published in Richard J. Sundberg, The Chemical Century, 2017
The crucial role of adrenaline, nor-adrenaline, dopamine, serotonin, and GABA as neurotransmitters made them appealing targets in the search for other drugs for treatment of neurological and psychological disorders. The general hypothesis that developed was that the levels of the neurotransmitters affected mood and behavior. In particular, deficiencies in the monoamine neurotransmitters were associated with depression. The observation that an antituberculosis drug, iproniazid had antidepressant effects, based on inhibition of the enzyme monoamine oxidase (MAO), led to one group of antidepressants called monoamine oxidase inhibitors (MAOI). Other drugs that had no MAOI activity were found to have antidepressant activity, such as imipramine. Its activity was found to be associated with the inhibition of uptake of noradrenaline at synapses. This led to discovery of other drugs that were both non-selective and selective among the neurotransmitters. They are classified as monoamine uptake inhibitors.
Xenobiotic metabolism and transport in Caenorhabditis elegans
Published in Journal of Toxicology and Environmental Health, Part B, 2021
Jessica H. Hartman, Samuel J. Widmayer, Christina M. Bergemann, Dillon E. King, Katherine S. Morton, Riccardo F. Romersi, Laura E. Jameson, Maxwell C. K. Leung, Erik C. Andersen, Stefan Taubert, Joel N. Meyer
Monoamine neurotransmitters such as dopamine and serotonin are degraded in humans by monoamine oxidases MAO-A and MAO-B. These enzymes also act on xenobiotics that are structurally similar to their natural substrates. C. elegans has a single ortholog of these genes, amx-2 (Schmid et al. 2015), which was demonstrated to metabolize serotonin in the worm (Wang et al. 2017) and presumably would have overlapping specificity with MAO-metabolized xenobiotics identified in mammalian systems.