Selective serotonin uptake inhibitor

Two recently introduced antidepressants are notable m that they are selective serotonin uptake inhibitors Citalopram (19) is reported to be as effective as amitriptyline m the treatment of endogenous depression [75, 16] Fluoxetine (20) as the hydrochlonde is approved for major depressive disorders mcludmg those with concomitant anxiety Interestmgly, it also appears useful m the treatment of obesity [17]... 

The radiosynthesis of [ F] fluoxetine, a selective serotonine uptake inhibitor (Scheme 62), is one of the rare examples in which a Br atom has been substituted for an F isotope [248]. It suffers from a low specific radioactivity due to decomposition of starting material. 

Selegiline should not be coadministered with tricyclic antidepressants or selective serotonin uptake inhibitors because of the possibility of a severe adverse drug reaction (e.g., hyperpyrexia, agitation, delirium, coma). 

Hostetter, A., Stowe, Z.N., Strader, J.R., Jr., McLaughlin, E., Llewellyn, A. (2001) Dose of selective serotonin uptake inhibitors across pregnancy clinical implications. Depress Anxiety, 11 51-57. 

Wong, D.T., Fuller, R.W., and Robertson DW. (1990) Fluoxetine and its two enantiomers as selective serotonin uptake inhibitors. Acta Pharm Nord 2 171-180. 

Considerable attention has been paid to the ultimate postsynaptic effects of increased neurotransmitters in the synapses. In tests of postsynaptic effects, cAMP concentrations have consistently decreased rather than increased, in spite of the presumably longer duration of action of the transmitters. In addition, the number of postsynaptic -adrenoceptors has shown a measurable decrease that follows the same delayed time course as clinical improvement in patients. Thus, the initial increase in neurotransmitter seen with some antidepressants appears to produce, over time, a compensatory decrease in receptor activity, ie, down-regulation of receptors. Decreases in norepinephrine-stimulated cAMP and in B-adrenoceptor binding have been conclusively shown for selective norepinephrine uptake inhibitors, those with mixed action on norepinephrine and serotonin, monoamine oxidase inhibitors, and even electroconvulsive therapy. Such changes do not consistently occur after the selective serotonin uptake inhibitors, 2 receptor antagonists, and mixed serotonin antagonists. 

Miura, H., Kitagami, T., Ozaki, N. (2007). Suppressive effect of paroxetine, a selective serotonin uptake inhibitor, on tetrahydrobiopterin levels and dopamine as well as serotonin turnover in the mesoprefrontal system of mice. Synapse, 61, 698-706. 

Figure 2.17 The structural analogs talopram 58 and citalopram 59 (upper compounds), as well as nisoxetine 60 and fluoxetine 61 (lower compounds), are chemically closely related. Whereas 58 and 60 (left compounds) are highly selective norepinephrine uptake inhibitors (selectivity factors of 550 and 180, respectively), the close analogs 59 and 61 (right compounds) are selective serotonin uptake inhibitors (selectivity factors of 3400 and 54, respectively).

Wong, D.T. er a/. (1995) Prozac (fluoxetine. Lilly 110140). the first selective serotonin uptake inhibitor and an antidepressant drug Twenty years since its first publication. Life Sci. 57.411-441. 

Citalopram [ban. inn] (nltalapram Lu 10-171 Clpramil ) is a carbonitrile, a selective serotonin uptake inhibitor and a recently introduced antidepressant of the SSRI (selective serotonin (re) uptake inhibitor) group. It is used orally to treat depressive illness and panic disorders. 

Wong. D.T. etal. (1995) Development of antidepressant drugs. Fluoxetine (Prozac) and other selective serotonin uptake inhibitors. Adv Exp. Med. Biol., 363.77-95. 

Fluoxetine, a selective serotonin uptake inhibitor (SSUI), (20 mg p.o./day) is indicated in the treatment of depression and depressive compulsive disorder (see Figure 51). 

Robertson, D.W. Krushinski, J.H. Fuller, R.W. Leander, J.D. Absolute configurations and pharmacological activities of the optical isomers of fluoxetine, a selective serotonin-uptake inhibitor. J.Med.Chem., 1988, 31, 1412-1417... 

The antidepressant class of drugs are well-known and widely used today not only for the treatment of mood disorders, such as depression and bipolar disorders, but also for the treatment of neuropathic pain, smoking cessation, and obsessive-compulsive disorders, among others. The application of medicinal chemistry in the development of newer antidepressants, such as selective serotonin uptake inhibitors... 

Bymaster, ER, Zhang, W., Carter, R, Shaw, J., Chernet, E., Rhebus, L., Wong, D. and Rerry, K.W. (2002) Eluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex. Psychopharmacology (Berl), 160 353-61. 

The hypothesis that serotonin dysfunction may play an important role in depression and the fact that tricyclic antidepressants are monoamine uptake inhibitors but also have a considerable affinity as antagonists for cholinergic, histaminergic and adrenergic receptors and thus may cause unwanted severe side-effects initiated the search for and development of selective serotonin uptake inhibitors. 

Other consequences were less serious, in that they did not present immediate threats to life, but were certainly serious for the patient. For instance, one patient suffered prolonged sexual dysfunction after his doctor failed to stop a selective serotonin uptake inhibitor another had continued sleep disturbance due to taking an anti-depressant that his doctor was not aware of. Such reactions represent prolonged, avoidable suffering over many months, to say nothing of the waste of time and resources. If these findings were replicated across the United States, the cost implications would be staggering. 

Robertson DW, Jones ND, Swartzendruber JK, Yang KS, Wong DT. Molecular structure of fluoxetine hydrochloride, a highly selective serotonin-uptake inhibitor. J. Med. Chem. 1988 31(1) 185-185. 

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