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Drugs for Treatment of Neurological and Psychological Conditions
Published in Richard J. Sundberg, The Chemical Century, 2017
The lifetime prevalence of depression in the United States is around 15%. Depression is a major factor in both disability and health-care costs worldwide. There are a few physiological features that seem to be associated with depression, including enlargement of the pituitary and adrenal glands and increased cortisol levels, suggesting the involvement of the hypothalamic–pituitary–adrenal axis. These effects are believed to be caused by an increased level of corticotrophin-releasing factor, which is involved in the stress response (see Section 15.2). So far however, no drugs have been developed based on these relationships. The currently available antidepressant drugs are targeted to the monoamine neurotransmitters. Their effects are to increase the levels of noradrenaline, dopamine, and serotonin. The amino acid neurotransmitters, glutamate, and GABA have also been the subject of studies searching for relationships to depression, but there are no antidepressant drugs that are thought to act directly on glutamate or GABA receptors.13 One feature of most antidepressant drugs is that the beneficial effects are not immediate, but rather require several weeks of treatment before improvement is noted. Most also have at least some undesirable side effects.
Fluoride and human health: Systematic appraisal of sources, exposures, metabolism, and toxicity
Published in Critical Reviews in Environmental Science and Technology, 2020
Humayun Kabir, Ashok Kumar Gupta, Subhasish Tripathy
A series of clinical and experimental studies conducted in India and China have proposed that ingestion of excess F− affects the intelligence of children (Aravind et al., 2016; Barberio, Quiñonez, Hosein, & McLaren, 2017; Jiang et al., 2019; Saxena et al. 2012; Zhao, Liang, Zhang, & Wu, 1996). Insufficient data on neurotoxicity and inadequate control of influencing factors have prevented F− from being considered an endocrine disruptor. However, F− may be responsible for the gradual deterioration of the central nervous system and alterations in brain function (ATSDR, 2003). Because the developing brain is highly responsive to excess F−, poor mental development may result. Cerebrospinal fluid (CSF) also contains F− as a constituent at a concentration slightly lower than that in plasma. The blood-brain barrier maintains CSF F− concentrations by resisting free movement of F− ions. Excess F− in CSF may generate free radicals and peroxides, which have a direct cytotoxic effect on CSF and brain tissue (Strunecka, Patocka, Blaylock, & Chinoy, 2007). Fluoride also can cause neurotoxicity and decrease neurotransmission by inducing metabolic dysfunction, altering monoamine neurotransmitter levels, and disrupting the cell-cycle and DNA in animal brain cells (Liu et al., 2014; Shashi, Singh, & Thapar, 1994; Zhang, Wang, Xia, & He, 2008).