Serotonin concentrations

Romero, L., Jemej, B., Bel, N., Cicin-Sain, L., Cortes, R., and Artigas, F., Basal and stimulated extracellular serotonin concentration in the brain of rats with altered serotonin uptake, Synapse 28(4), 313-321, 1998. 

In the late 1960s, different types of cyclopropylamines, the A/-substituted cyclopropylamines, were reported [111]. One of the most interesting compounds in the new class was A/-[2-o-chlorophenoxy]-ethyl]-cyclopropylamine (Lilly 51641) (42). This compound noncompetitively inhibited the MAO-catalyzed oxidation of serotonin, tyramine, phenylethylamine, and tryptamine in vitro and increased the serotonin concentration in the whole rat brain in vitro. In structure-activity studies on a series of m- and p-aromatic substituted A/-(phenoxyethyl)cyclopropylamines (43), the degree of inhibition correlated well with a and % values [112]. 

Some authors (Flament et ah, 1987) found that response to treatment with clomipramine was correlated with a marked decrease in platelet serotonin concentration and monoamine oxidase (MAO) activity. Changes in cerebrospinal fluid (CSF) neuropeptides and monoamine metabolites have also been described with chronic clomipramine administration (Swedo et ah, 1992 Altemus et ah, 1994). Despite these observations, the exact mechanism of action of serotonergic drugs (and the serotonin hypothesis ) remains unproven, although it is thought they mediate their effects via down-regulation of the presynaptic 5-HTlD autoreceptor (Rauch et ah, 1994). 

The postsynaptic physiological effects of serotonin are varied and widespread. The administration of serotonin leads to powerful smooth-muscle effects in the cardiovascular and gastrointestinal systems. Vasodilation and hypotension may result, partly through central effects, if the serotonin concentration in the CNS is increased by administration of the serotonin precursor 5-hydroxytryptophan. Unlike serotonin, this precursor can cross the blood-brain barrier. Intestinal mobility is also influenced by serotonin. 

During Ecstasy Elsvated mood due to increased serotonin concentration in synaptic cleft... 

Just as the acute increase in serotonin concentration causes a pleasurable state and heightened mood, the crash that follows Ecstasy use can also be explained at the biological level. While taking MDMA, serotonin is being released from neurons while reabsorption back into the neurons is blocked (Figure 2.4). 

The hypothesis that SSRIs work in OCD by a serotonergic mechanism is also supported by studies showing a strong positive correlation between improvement in obsessive-compulsive symptoms during clomipramine treatment and drug-induced decreases in cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and platelet serotonin concentrations. Thus, peripheral markers of 5HT function link the symptomatic improvement in OCD symptoms produced by SSRIs to changes in 5HT function. However, these markers do not consistently highlight a 5HT abnormality in untreated patients with OCD,... 

SSRIs increase serotonin concentration at synapses, which may be responsible for diminishing repetitive behaviours. 

SSRIs CARBAMAZEPINE Risk of serotonin syndrome with carbamazepine Carbamazepine t serotonin concentrations in the brain Avoid co-administration... 

Theoretically due to increases in serotonin concentrations at serotonin receptors in parts of the brain and body other than those that cause therapeutic actions (e.g., unwanted actions of serotonin in sleep centers causing insomnia, unwanted actions of serotonin in the gut causing diarrhea, etc.)... 

A recent study showed that immunotherapy with IFN-a was follov ed by an increase of depressive symptoms and serum kynurenine concentrations on the one hand, and reduced concentrations of tryptophan and serotonin on the other hand (Bonaccorso et al., 2002). The kynurenine/tryptophan ratio, which reflects the activity of IDO, increased significantly. Changes in depressive symptoms v ere significantly positively correlated vdth kynurenine and negatively correlated with serotonin concentrations (Bonaecorso etal., 2002). This study and others (Capuron et al., 2003) clearly show that the IDO activity is increased by IFN, leading to an increased kynurenine production and a depletion of tryptophan and serotonin. The further metabolism of kynurenine, however, seems to play an additional crucial role for the psychopathological states. 

Specific serotonin reuptake inhibitors, as the class name implies, act predominantly by preventing serotonin reuptake and have more limited effects on noradrenaline reuptake. Tricyclic antidepressants in general inhibit noradrenaline reuptake, but effects on serotonin reuptake vary widely desipra-mine and protriptyline have minimal potential for raising serotonin concentrations, whereas clomipramine possesses a greater propensity for blocking serotonin reuptake than for noradrenaline. The... 

The clinical chemical evaluation of the carcinoid syndrome relies on measurements of serotonin and its metabo-htes in body fluids and tissue. In patients with the typical carcinoid syndrome, 5-HTP is converted to serotonin and stored in tumor secretory granules and in platelets. A small amoxmt of serotonin remains in plasma, but most is converted to 5-HIAA, which is excreted in urine. These patients have increased blood and platelet serotonin levels and increased urinary 5-HIAA. However, some foregut carcinoid tumors lack the aromatic L-amino acid decarboxylase and secrete 5-HTP rather than serotonin into the bloodstream. Patients with these tumors have normal serotonin concentrations in blood and in platelets, but urinary levels are increased because 5-HTP is converted to serotonin in the kidney urinary 5-HIAA levels may be slightly elevated. 

Platelet-rich plasma samples are prepared from whole blood by centrifuging at 120g for 30 minutes at 4 or at 200 for 15 minutes at room temperature. To prevent lowering the serotonin concentration, platelet-rich plasma is prepared within 1 hour after the blood is collected and placed on ice. An aliquot of platelet-rich plasma is removed for a platelet count. Platelet-poor plasma and platelet pellets are prepared from measured aliquots of the platelet-rich sample plasma by centrifuging at 4500 for 10 minutes at 4 (or at lOOOg for 30 minutes at room temperature). To reduce the probability of platelet rupture, samples should never be frozen before the cell-free plasma is obtained. Plasma and pellets are stored frozen at -20 °C and analyzed within 1 to 2 weeks after collection. 

Flachaire E, Beney C, Berthier A, Salandre J, Quincy C, Renaud B. Determination of reference values for serotonin concentration in platelets of healthy newborns, children, adults, and elderly subjects by HPLC with electrochemical detection. Clin Chem 1990 36 2117-20. 

Harper AE, Peters JC. 1989. Protein intake, brain amino acid and serotonin concentrations and protein self-selection. J Nutr 119 677-689. 

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