Subject selective serotonin reuptake inhibitors

Recent evidence indicates that the 5-HT transporter is subject to post-translational regulatory changes in much the same way as neurotransmitter receptors (Blakeley et al. 1998). Protein kinase A and protein kinase C (PKC), at least, are known to be involved in this process. Phosphorylation of the transporter by PKC reduces the Fmax for 5-HT uptake and leads to sequestration of the transporter into the cell, suggesting that this enzyme has a key role in its intracellular trafficking. Since this phosphorylation is reduced when substrates that are themselves transported across the membrane bind to the transporter (e.g. 5-HT and fi -amphetamine), it seems that the transport of 5-HT is itself linked with the phosphorylation process. Possibly, this process serves as a homeostatic mechanism which ensures that the supply of functional transporters matches the demand for transmitter uptake. By contrast, ligands that are not transported (e.g. cocaine and the selective serotonin reuptake inhibitors (SSRIs)) prevent the inhibition of phosphorylation by transported ligands. Thus, such inhibitors would reduce 5-HT uptake both by their direct inhibition of the transporter and by disinhibition of its phosphorylation (Ramamoorthy and Blakely 1999). 

Oberndorfer, S., Saletu-Zyhlarz, G. Saletu, B. (2000). Effects of selective serotonin reuptake inhibitors on objective and subjective sleep quality. Neuropsychobiology 42, 69 81. 

Structure is also essential in complex biological molecules. A lot of medicines used for psychiatric illnesses such as depression rely on their ability to interact with certain proteins in the brain. For instance, a class of antidepressants—medications that alleviate the symptoms of depression—act on proteins involved with the collection (reuptake) of the chemical serotonin, and they are known as selective serotonin reuptake inhibitors (SSRIs). This class of antidepressants includes Prozac and Zoloft. Earlier medications were also effective and are still sometimes used though they produce a number of side effects, such as dietary problems. Although an SSRI can also generate potentially dangerous side effects, psychiatrists tend to observe these effects less often. (Brain chemistry is the subject of chapter 3.)... 

Treatment of cerebral stroke patients with selective serotonin reuptake inhibitor antidepressant showed difference in improvement with respect to laterality. The post-stroke major depressive disorder improved much more in right stroke subjects in comparison with the left stroke ones (Spalletta el al., 2003). In case of unilateral brain injury due to stroke or parkinsonism, the intact hemisphere plays an important role in recovery and compensation for the lost motor function (Schallert el al., 2003). A well-selected homeopathic potency may facilitate recovery by acting on the intact hemisphere. It has been demonstrated that the brain can asymmetrically... 

We recently investigated whether the administration of a selective serotonin reuptake inhibitor, fluvoxamine, could interfere with the sleep patterns induced after TED. In this double-blind placebo-controlled cross-over study, 12 healthy male volunteers aged 18-40 years were assigned to two treatment conditions tryptophan or sham depletion and fluvoxamine or placebo. During each session, separated by a 2-day wash-out period, subjects took either fluvoxamine or placebo and either tryptophan... 

The cause or causes and the meaning of the elevation of platelet 5-HT observed in some autistic patients is unknown, but the serotonin transporter (5-HTT) is thought to be involved as it controls the rate of reuptake of serotonin from the synaptic cleft. The fact that selective serotonin reuptake inhibitors ameliorate obsessive compulsive symptoms, stereotypies, affective liability and social relatedness in some subjects with autism [16, 17], lends further support for this hypothesis. After... 

The stereoselective pharmacokinetics of the selective serotonin reuptake inhibitor, citalopram, have been studied in 10 healthy young subjects [139]. After administration of 40 mg racemate daily for 21 days by the oral route, stereoselectivity was found in citalopram plasma concentrations. The R(—) S(+) ratios of Cmax and AUCss were 1.5 and 1.6, respectively. No difference was noted in suggesting similar absorption rates of the enantiomers. The terminal phase values were 47 and 35 h for the R and S enantiomers, respectively. Renal clearance comprised 20% of each enantiomer s total clearance and was nonstereoselective. Although both enantiomers are extensively metabolized, both possess low hepatic extraction ratios [139]. Serotonin reuptake inhibition of citalopram primarily resides with the S enantiomer (see Chap. 5, Sec. 3.4 for more details), which attains lower concentrations in plasma. In eight geriatric patients (mean 77 y) given... 

In a similar study, however, reduced Glx levels were observed in the anterior cingulum of depressed patients. The level of Glx was found to increase upon effective ECT." The effects of selective serotonin reuptake inhibitor discontinuation syndrome have been investigated in patients with unipolar major depression who had been stabilised on paroxetine or fluoxetine. H NMR spectroscopic imaging of the rostral anterior cingulate was carried out 3 days after substitution of medication with a selective serotonin reuptake inhibitor or a placebo. The ratio of Cho/tCr was deceased in patients who met the criteria of selective serotonin reuptake inhibitor discontinuation syndrome compared to asymptomatic subjects." ... 

Fluvoxamine. The second placebo-controlled study of a serotonin reuptake inhibitor in the treatment of social phobia to date involved fluvoxamine [Den Boer et al. 1994]. Thirty subjects with social phobia according to DSM-III-R criteria were randomly selected in a double-blind fashion in this 12-week study. At the end of this period, subjects who judged themselves as clinically improved were allowed to continue for an additional 12 weeks. Fourteen of 16 subjects in the fluvoxamine group opted to continue. No subjects in the placebo group proceeded into the follow-up phase of treatment. Fluvoxamine showed superiority to placebo on nearly all psychometric measures. 

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