Serotonin precursor

Pharmacology Trazodone selectively inhibits serotonin uptake by brain synaptosomes and potentiates the behavioral changes induced by the serotonin precursor, 5-hydroxytryptophan. 

Studies in which the availability of serotonin is manipulated in combination with a laboratory panic challenge has considerably increased insight into the relationship between serotonin and panic disorder. Tryptophan depletion caused an increased panic response to a 5% or 35% CO2 challenge in panic disorder patients (Miller et al. 2000 Schruers et al. 2000). Conversely, panic anxiety and symptoms, as well as the number of panic attacks following 35% CO2 inhalation, were significantly reduced by pretreatment with the serotonin precursor L-hydroxytryptophan, suggesting that under certain circumstances serotonin may act to inhibit panic (Schruers et al. 2002). 

A recent positron emission tomography (PET) study in which the radiolabeled serotonin precursor alpha C methyl tryptophan was used provides empirical evidence of decreased 5-HT synthesis in frontal and thalamic regions and increased 5-HT synthesis in contralateral cerebellar dentate regions (Chugani et al., 1997). These findings are consistent with findings of increased 5-HTm inhibitory autoreceptor sensitivity in adult autistic patients (Hollander et al., 2000 Novotny et al., 2000), since these receptors are prevalent in frontal and thalamic, but not cerebellar, regions. 

Kahn RS, Westenberg HGM L-5-Hydroxytryptophan in the treatment of anxiety disorders. J Affect Disord 8 197-200, 1985 Kahn RS, Westenberg HGM, Verhoeven WMA, et al Effects of a serotonin precursor and uptake inhibitor in anxiety disorders a double-blind comparison of 5-hydroxytryptophan, clomipramine and placebo. Int J Clin Psychopharmacol 2 33-45, 1987... 

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. 

Serotonin precursors (L-tryptophan. 5-hydroxytryptophan) have some antidepressant action, whereas a reduction in the blood levels of tryptophan in remitted depressed patients can provoke clinical relapse. 

Van Praag HM. Management of depression with serotonin precursors. Bid Psychiatry 1981 16 291-310. 

In children who drink juices containing aspartame, hypersensitivity has been observed and an increased tendency toward aggressive behavior has been observed. It has been found that aspartame intake leads to doubling phenylalanine concentration in the central nervous system. Also an increase in tyrosine has been observed, followed by a decrease of tryptophan—a serotonine precursor. Low CNS serotonine in children has been found to be responsible for neurosis symptoms. 

In all organisms 5HT (Serotonin) precursor Elelianthus annuus (Asteraceae), Phaseolus vulgaris (Fabaceae), Oenothera biennis (Onagraceae) [seed]... 

Another test for the biogenic amine hypothesis w ould involve precursor loading sLategies. In other w ords, compounds w hich could increase brain levels of norepinephrine and/or serotonin should demonsLate antidepressant efficacy. Results of these studies have been mixed. Several positive findings w ere reported wdth Seating depression wdth the serotonin precursors tryptophan and 5-hydroxy tryptophan (5-HT) (Shaw et al., 2001), but these w ere not consistently replicated. Less posidve results w ere reported wdth attempts to increase brain norepinephrine levels wdth precursors. 

Lithium s serotonergic activity is postulated to be responsible for its role in preventing depressive episodes of bipolar disorder. Some bipolar patients demonstrate low CNS concentrations of serotonin. Lithium may contribute to serotonin production by increasing the uptake of the tryptophan, a serotonin precursor (American Society of Hospital Pharmacists 1993). 

The involvement of the central nervous system serotonin function in the pathogenesis and treatment of affective disorders has been a subject of intensive research during the past 30 years.33 36 Studies using serotonin precursors and agonists as pharmacologic probes and measurements of cerebrospinal fluid monoamine metabolite levels indicated that alterations in central nervous system serotonin function may be involved in the pathophysiology of depression. Since the synthesis of serotonin depends on dietary intake of the precursor tryptophan, many studies have utilized tryptophan depletion techniques by which patients were fed a tryptophan-free diet for various time intervals. 

Many reports have linked childhood hyperactivity to impaired central serotonin functions.89 In animals, the occurrence of a behavioral syndrome consisting of hyperactivity, stereotyped movements, and increase of temperature has been induced by L-tryptophan, as a serotonin precursor, by serotonin reuptake inhibitors, and by MAOIs.90 Most of these manifestations can be blocked specifically by pretreatment with an inhibitor of serotonin synthesis. In humans, the association of myoclonus, diarrhea, confusion, hypomania, agitation, hyperreflexia, shivering, incoordination, fever, and diaphoresis, when patients are treated with serotoninergic agents, could constitute a "serotonin syndrome." Such cases of serotonin syndrome were reported after treatments with L-tryptophan, MAOIs, serotonin reuptake inhibitors, and tricyclics, alone or in association. 

Fig. 14.2. Steps involved in serotonergic neurotransmission. The serotonin precursor tryptophan is taken up into the neuron (A) and converted to 5-HT (B). Synthesized 5-HT Is stored in synaptic vesicles (C). Under the appropriate conditions, the synaptic vesicles migrate to and fuse with the cell membrane, releasing their store of 5-HT (D).

Serotonin plays a role in the modulation of social behavior and in reward processing. Deficiency of tryptophan, the serotonin precursor, leads to reduction in serotonin production, and brings about reductions in the level of cooperation shown by participants in an experimental game-playing experiment. Serotonin also plays a role in socially... 

Bogdanski, D. F., Weissbach, H. and Udenfriend, S., Pharmacological studies with the serotonin precursor, 5-hydroxytryptophan, J. Pharmacol. Exp. Ther. 122, 182... 

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