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High Information Content Physiological Biosensors
Published in George K. Knopf, Amarjeet S. Bassi, Smart Biosensor Technology, 2018
Guenter W. Gross, Joseph J. Pancrazio, Kamakshi Gopal
The NNBS was used for a survey of serotonergic and noradrenergic effects in an attempt to quantify responses and compare them to clinical results. As a first step, fluoxetine (Prozac) was selected because of common usage and reports of deaths (Spier and Frontera, 1991; Goeringer et al., 2000; Sallee et al., 2000; Chopra et al., 2004), and because acute effects had not been quantified. Decreased serotonergic neurotransmission is thought to play an important role in depression, and fluoxetine is a selective serotonin reuptake inhibitor that is widely used clinically in the treatment of depression. The primary action of fluoxetine is to selectively inhibit serotonin reuptake into the presynaptic cell by blocking the 5-HT transporters, thus increasing the level of serotonin in the synaptic cleft for binding to the postsynaptic receptor. The optimal clinical dose range recommended is 20–40 mg/day, which translates to a plasma concentration of approximately 1 μM (Altamura et al., 1994). As fluoxetine is lipid soluble with a high brain-to-blood ratio, the brain concentration is close to 20 μM (Karson et al., 1993; Tsuneizumi et al., 1992).
Drugs for Treatment of Neurological and Psychological Conditions
Published in Richard J. Sundberg, The Chemical Century, 2017
The first selective serotonin reuptake inhibitors (SSRI) to be approved in the United States was fluoxetine (Prozac) in 1987. It was developed and marketed by Eli Lilly. It became a very successful drug, including being named “Pharmaceutical Product of the Century” by Fortune Magazine in 1999. Peak annual sales in the United States were $2.8 billion in 1998. Fluoxetine was developed on the basis of the hypothesis that selective inhibition of serotonin uptake might be useful in treatment of depression. Serotonin’s role in neurotransmission had become fairly widely appreciated by the late 1960s. The “serotonin hypothesis” attributed special importance to serotonin levels in depression and psychoses. The group at Lilly used “synaptosomes,” a particulate fraction consisting of nerve ending that had the capacity for production and release of the monoamine neurotransmitters. The assay was used to search for selective inhibitors. Many analogs of diphenhydramine (also the original lead compound for the tricyclic antidepressants) were synthesized. Among these, fluoxetine was found to be highly selective for serotonin relative to noradrenaline. Various other assays confirmed this selectivity. The results were first reported in 1974. An IND study was approved in 1976. In clinical studies, fluoxetine did not exhibit the side effects associated with the cholinergic, adrenergic, or histamineric effects of the tricyclic antidepressants. The NDA was submitted in 1983 and final approval was obtained at the very end of 1987. In addition to treating depression, fluoxetine is used for treatment of eating disorders such as anorexia and bulimia.
Centella asiatica L. Urban protects against morphological aberrations induced by chronic unpredictable mild stress in rat’s hippocampus via attenuation of oxidative stress
Published in Egyptian Journal of Basic and Applied Sciences, 2022
Saravanan Jagadeesan, Samaila Musa Chiroma, Mohamad Aris Mohd Moklas, Mohamad Taufik Hidayat Baharuldin, Che Norma Mat Taib, Zulkhairi Amom, Thirupathirao Vishnumukkala, Warren Thomas, Onesimus Mahdi
The current drug treatment for depression is based on selective serotonin reuptake inhibitors (SSRI’s), monoamine oxidase inhibitors (MAOI’s), and tricyclic antidepressants (TCA’s). These treatments have significantly contributed to enhancing the quality of life of individuals with depression, but they are not without their limitations. The current medications do not produce a uniform response among patients, it takes weeks for their effects to be observed and many treatments have significant side effects [16]. The concurrent use of multiple drugs complicates the problems through complex interactions and in particular gives rise to uncertainty regarding their safe use in pregnancy [17]. Fluoxetine is a commonly used antidepressant, and as an SSRI, it inhibits the serotonin transporters at the synaptic cleft. Though in wide use, fluoxetine has side effects including fatigue, weight gain, and sexual dysfunction [18,19]. Thus, though there is a wide range of medications available for the treatment of depression, none of them are universally effective or without side effects. Consequently, there is a need for new therapeutic agents with lesser side effects and broader efficacy [20]. In order to achieve this, it is necessary to consider the critical physiological processes that contribute to stress and depression.