Pharmacological analysis of the myoclonus induced by 5-hydroxytryptophan in the guinea pig suggests the presence of multiple 5-hydroxytryptamine receptors in the brain

Myoclonus induced in guinea pigs by administration of l-5-hydroxytryptophan (5-HTP) appears to be due to stimulation of central 5-HT receptors. Dose-dependent myoclonus was induced by administration of 5-HTP (with carbidopa pretreatment), l-tryptophan and tryptamine (both with pargyline pretreatment). and also by N,N-dimethyltryptamine, 5-metoxy-N,N-dimethyltryptamine and d-lysergic acid diethylamide (LSD). The synthetic 5-HT agonists quipazine, MK-212 and 1-(m-trifluoromethylphenyl) piperazine, however, evoked only occasional myoclonus at toxic doses. Antagonists of 5-HT receptors differed markedly in their ability to inhibit 5-HTP-induced myoclonus; while methergoline and cyproheptadine were potent inhibitors, mianserin, methysergide and BW 501C67 only caused effective inhibition in large doses. Similarly, 5-HT re-uptake blockers showed different activities in potentiating the effects of a threshold dose of 5-HTP; myoclonus was greatly potentiated by chlorimipramine, paroxetine and Org 6582, while femoxetine, fluoxetine and desmethylimipramine were only weakly active.The lack of uniform effects of the 5-HT agonists, antagonists and re-uptake blockers studied is not attributable entirely to their variable actions on central 5-HT mechanisms, to their effects on other brain neuronal pathways, or to differences in cerebral penetration. The data may provide functional evidence for a multiplicity of cerebral 5-HT receptors.     

Plasma Accumulation and Metabolism of Orally Administered Single Dose L-5-Hydroxytryptophan in Man

Abstract: Single oral doses of L-5-hydroxytryptophan (5-HTP) were administered in combination with L-aromatic amino acid decarboxylase inhibitors. The time courses of plasma concentrations of 5-HTP, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) and the concentrations of 5-HT in blood platelets were measured. Carbidopa enhanced the rise in plasma concentrations of 5-HTP 5–15 fold and counteracted the increase in plasma 5-HIAA levels induced by 5-HTP alone. A single dose of the decarboxylase inhibitor was equipotent to 14 days' pretreatment. Plasma or platelet concentrations of 5-HT failed to reflect the metabolism of 5-HTP. The ratio of 5-HTP to carbidopa influenced the systemic bioavailability of single dose administered 5-HTP indicating dose dependent absorption kinetics. Co-administration of L-dopa with 5-HTP and decarboxylase inhibitors had no effect on gastrointestinal absorption of 5-HTP in six parkinsonian patients.     

l-5-Hydroxytryptophan: Correlation between anticonvulsant effect and increases in levels of 5-hydroxyindoles in plasma and brain

The effect of l-5-hydroxytryptophan (5-HTP) on the threshold for maximal electroconvulsions was compared with concomitant changes in levels of 5-HTP, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in plasma and brain of rats. A single injection of 5-HTP (100 $\text{mg}\text{kg}$, i.p.) caused significant elevation in seizure threshold which was markedly intensified by pretreatment with the decarboxylase inhibitor carbidopa (10 $\text{mg}\text{kg}$, i.p., 0.5 hr previously). Pretreatment with carbidopa also resulted in behavioural changes, i.e. the characteristic “wet-dog shake” behaviour became much more prominent. Biochemically, administration of 5-HTP gave rise to significant elevation of levels of 5-HTP, 5-HT and 5-HIAA in plasma and brain. Carbidopa increased levels of 5-HTP in the brain, decreased 5-HIAA in the periphery but did not alter the elimination rate of 5-HTP in plasma. In both naive rats and rats pretreated with carbidopa, a significant correlation was found between levels of 5-HTP and 5-HIAA in plasma and brain following injection of 5-HTP. Furthermore, in the absence of carbidopa, the increases of levels of 5-HT in plasma and brain induced by 5-HTP were correlated in a significant fashion. When the changes in the electroconvulsive threshold were compared with respective changes in levels of 5-hydroxyindoles, a significant correlation was obtained between threshold elevations and increases of 5-HTP and 5-HT in the brain. In rats treated with 5-HTP, without decarboxylase inhibitor, a significant correlation was found between increases in 5-HT in plasma and the seizure threshold. The results suggest that analysis of 5-hydroxyindoles in plasma may represent a useful tool for the estimation of 5-HT metabolism in brain.     

Neuroleptic influence on hyperthermia induced by 5-hydroxytryptophan and p-methoxy-amphetamine in MAOI-pretreated rabbits

5-Hydroxytryptophan (5-HTP) and p-methoxyamphetamine (p-MA) induced dose-dependent, lethal hyperthermia when applied intravenously to monoamine oxidase inhibitor (MAOI) pretreated rabbits. The time course of hyperthermia and the doses required to induce hyperthermia varies between the two substances. Results with -MT and PCPA suggest that 5-HTP hyperthermia depends on 5-HT formation, release of endogenous 5-HT, and the presence of catecholamines, whereas p-MA-induced hyperthermia most likely is a result of indirect 5-HT release.Some neuroleptics (piflutixol, spiroperidol and methiotepine) are extremely potent inhibitors of the induced hyperthermia. Also the 5-HT receptor blocking agent methergoline antagonizes hyperthermia induced by the two substances in rather low doses. On the other hand cis (Z)-flupenthixol is a very weak antagonist of 5-HTP but a more potent inhibitor of p-MA hyperthermia. It is concluded that both 5-HT and catecholamine (dopamine) receptor blockade is required to antagonize 5-HTP hyperthermia and that antagonism of p-MA induced hyperthermia is primarily a result of influence on the 5-HT system.Part of this work was presented at the 7th International Congress of Pharmacology, Paris, 1978     

The excretion of tryptophan metabolites in patients with different forms of haemoblastosis.

The urinary excretion of kynurenine, 3-hydroxykynurenine, kynurenic and xanthurenic acid has been determined by bidimensional paper chromatography in 61 patients with different forms of haemoblastosis (27 cases of Hodgkin's disease, 10 cases of non Hodgkin's lymphomas, 8 cases of acute leukaemia, 11 cases of myeloproliferative disorders, 5 cases of lympho-immunoproliferative disorders). An abnormal urinary excretion of some metabolites of tryptophan's kynurenine pathway is frequent but not constant in all the neoplasias of the myelolymphopoietic system studied so far. In Hodgkin's disease the correlative test between urinary excretion of tryptophan metabolites and clinical stage, histological type and treatment enabled us to point out that the anatomo-clinical diffusion of the lymphoma interferes only through kynurenine and 3-hydroxykynurenine excretion. The histological type seems to influence the 3-hydroxykynurenine excretion. On the contrary, the metabolic alterations present are not affected by treatment. We believe that the metabolic alteration of tryptophan is secondary to a deficit of pyridoxal phosphate and nicotinamide-dependent enzyme activities.     

Potent and long-lasting potentiation of two 5-hydroxytryptophan- induced effects in mice by three selective 5-ht uptake inhibitors.

The effect of i.p. administered 5-hydroxytrptophan (5-HTP) on electroschock seizures and motility was studied in mice. High doses (600–2000 mg/kg) produced an anticonvulsant effect and hypermotility. Both effects were inhibited by the central decarboxylase inhibitor NSD 1015 (100 mg/kg i.p.) and potentiated by the peripheral decarboxylase inhibitor Ro 4-4602 (5 mg/kg i.p.). The catecholamine sysnthesis inhibitor α-methyl-p-tyrosine or H $\text{44}\text{68}$ (100 and 200 mg/kg i.p.) did not alter the anticonvulsant effect but H $\text{44}\text{68}$ (200 mg/kg i.p.). inhibited the hypermotility. Six inhibitors of neuronal NA and 5-HT uptake were administered orally at various times before 5-HTP (150 mg/kg), which alone was devoid of anticonvulsant effect and produced a weak hypermotility. Low doses of the selective 5-HT-uptake inhibitors paroxetine, fluoxetine and zimelidine potentiated both 5-HTP-induced effects. The selective NA uptake inhibitor protriptyline showed no or weak 5-HTP potentiation. These results indicate that the anticonvulsant effect of 5-HTP is dependent on increased synthesis and release of brain 5-HT. Both 5-HT and catecholamine release are presumably involved in mediating 5-HTP-induced hypermotility since selective 5-HT uptake inhibitors were the strongest potentiators of this behavior. Increased serotoninergic neurotransmission seems to play an important role.     

A comparison of the locomotor effects of 5-hydroxytryptamine and 5-hydroxytryptophan administered via two systemic routes

This study compared the effects of systemically administered 5-hydroxytryptamine (5-HT) and 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP) on tilt cage locomotor activity in rats. 5-HT was a more potent inhibitor of activity than 5-HTP via both the s.c. and i.p. routes. The effect of 5-HT itself was greater when administered i.p., whereas the effects of 5-HTP were independent of the route of administration. These results indicate that behavioral changesfollowing 5-HTP injection may be attributable to the peripheral effects of 5-HT.     

The effects of 5-HT uptake- and MAO-inhibitors on l-5-HTP-induced excitation in rats

Summary The behavioural syndrome caused by l-5-HTP in rats was used for the study of effects of selective 5-HT uptake inhibitors and inhibitors of MAO on central 5-HT receptors. A good correlation was found between the relative potencies of drugs in inhibiting the 5-HT uptake in the rat brain and in intensifying l-5-HTP-induced behavioural stimulation. The potentiation of the l-5-HTP syndrome by the MAO inhibitors correlated with the inhibition of the A- but not of the B-form of the brain monoamine oxidase.In rats treated with the maximally inhibiting dose of a 5-HT uptake inhibitor, MAO inhibitors were still able to increase the intensity of the l-5-HTP syndrome, while the combination of maximal doses of two 5-HT uptake inhibitors did not produce a more intense syndrome than that produced by one 5-HT uptake inhibitor alone.The l-5-HTP-induced behavioural syndrome in rats seems to afford an experimental model allowing the quantification and characterization of the interaction of drugs with serotonin metabolism in the brain.     

A comparison of the effects on central 5-HT function of sibutramine hydrochloride and other weight-modifying agents

1. Effects on 5-HT function of sibutramine and its active metabolites, BTS 54 354 and BTS 54 505, were compared with fluoxetine, (+)-fenfluramine and (+)-amphetamine.
2. In vitro sibutramine weakly inhibited [³H]-5-HT uptake into brain synaptosomes. BTS 54 354, BTS 54 505 and fluoxetine were powerful [³H]-5-HT uptake inhibitors, whereas (+)-fenfluramine and (+)-amphetamine were very much weaker. Conversely, whilst sibutramine, its metabolites and fluoxetine did not release [³H]-5-HT from brain slices at ?10^?5M, (+)-fenfluramine and (+)-amphetamine concentration-dependently increased [³H]-5-HT release.
3. Sibutramine and fluoxetine had no effect on 5-hydroxytryptophan (5-HTP) accumulation in either frontal cortex or hypothalamus at doses <10 mg kg^?1. In contrast, (+)-amphetamine (?3 mg kg^?1) reduced 5-HTP in hypothalamus, whilst (+)-fenfluramine (?1 mg kg^?1) decreased 5-HTP in both regions.
4. Sibutramine (10 mg kg^?1 i.p.) and fluoxetine (10 mg kg^?1 i.p.) produced slow, prolonged increases of extracellular 5-HT in the anterior hypothalamus. In contrast, (+)-fenfluramine (3 mg kg^?1 i.p.) and (+)-amphetamine (4 mg kg^?1 i.p.) induced rapid, short-lasting increases in extracellular 5-HT.
5. Only (+)-fenfluramine (10 mg kg^?1) altered 5-HT_2A receptors in rat frontal cortex when given for 14 days, producing a 61% reduction in receptor number and a 18% decrease in radioligand affinity.
6. These results show that sibutramine powerfully enhances central 5-HT function via its secondary and primary amine metabolites; this effect, like that of fluoxetine, is almost certainly mediated through 5-HT uptake inhibition. By contrast, (+)-fenfluramine enhances 5-HT function predominantly by increasing 5-HT release. (+)-Amphetamine, though weaker than (+)-fenfluramine, also enhances 5-HT function by release.

     

Effect of triamterene on 5-hydroxytryptamine biosynthesis in different brain areas

Summary Triamterene is structurally similar to the natural cofactor of tryptophan hydroxylase, (6R)-l-erythro-5,6,7,8-tetrahydrobiopterin. The hydroxylation of tryptophan has been studied by measuring the accumulation of 5-hydroxytryptophan (5-HTP) and the concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in brainstem, frontal cortex and hypothalamus after inhibition ofl-amino acid decarboxylase with benserazide hydrochloride and administration of either the vehicle or triamterene. Triamterene (30 mg/kg i.p.) decreased 5-HTP accumulation and 5-HT concentrations in brainstem and hypothalamus after 90 min; when the diuretic was given p.o. either acutely or chronically (triamterene 30 mg/kg twice daily during 4 days), no effect either on 5-HTP accumulation or on 5-HT and 5-HIAA concentrations was observed in the three brain areas studied. These results are in accordance with the 4 to 5 times higher concentrations of triamterene plus metabolites found in brainstem and hypothalamus after the acute i.p. administration of the drug than after an acute or chronic p.o. treatment. Hence, the effect of triamterene on 5-HT biosynthesis depends on the concentration it reaches in each brain area after i.p. or p.o. administration.     

Effects of 5-Hydroxytryptophan on Arterial Blood Pressure,Body Temperature and Tissue Monoamines in the Rat

The mean arterial blood pressure in conscious rats was recorded by means of in-dwelling arterial catheters. DL-5-hydroxytryptophan (5-HTP) 200 mg/kg intraperitoneally lowered the blood pressure significantly after 20 min. Following the administration of the peripheral decarboxylase inhibitor L-α-hydrazino-α-methyl-β-(3,4-dihydroxyphenyl) propionic acid (MK 486) 100 mg/kg intraperitoneally, 5-HTP 200 mg/kg intraperitoneally caused only a slight lowering of the blood pressure after 1–2 hrs. 5-HTP 50 mg/kg given intraperitoneally after a combined pretreatment with a MAO inhibitor (nialamide) 100 mg/kg intraperitoneally and MK 486 100 mg/kg produced characteristic effects on gross behaviour after 20 min. No significant effects of 5-HTP on the blood pressure were observed in these experiments. 5- HTP 200 mg/kg intraperitoneally caused a hypothermia which was prevented by MK 486 100 mg/kg. After pretreatment with nialamide and MK 486 as in the blood pressure experiments, 5-HTP 50 mg/kg produced an initial hypothermia followed by a pronounced rise in body temperature. 5-HTP 200 mg/kg intraperitoneally resulted in a marked accumulation of 5-hydroxytryptamine (5-HT) in the heart and brain. Pretreatment with MK 486 100 mg/kg prevented the increase in heart 5-HT but did not change that in the brain. Brain dopamine (DA) but not brain and heart noradrenaline (NA) decreased significantly. 5-HTP 50 mg/kg after the administration of nialamide and MK 486 increased the brain 5-HT but caused no change in heart 5-HT. Nialamide and MK 486 per se increased brain DA and NA significantly; 5-HTP largely prevented the increase in brain DA but not in brain NA. It is concluded that 5-HTP has a hypothermic and a hypotensive action due to the effect of 5-HT on the extracerebral structures, while the hyperthermic effect may have a central nervous origin. 5-HT formed from 5-HTP lowers brain DA by displacement.     

Interactions of cerebral serotonin and catecholamines

It has been demonstrated that the administration of large doses of dopa or 5-hydroxytryptophan (5-HTP) affected not only dopamine (DA) or serotonin (5-HT) neurons but also other neurons. This report concerns the effects of tryptophan, 5-HTP or dopa on concentrations of 5-HT, DA, norepinephrine, and their metabolites in p-chlorophenylalanine-, 5,7-dihydroxytryptamine (5,7-DHT)- or non-treated rat brain. The results were as follows: 1) When the brain DA levels increased more than six-fold after the i.p. administration of l-dopa, the brain 5-HT levels significantly decreased, and 5-hydroxyindoleacetic acid (5-HIAA) levels significantly increased. 2) In the nerve ending fraction of rat brain, the administration of l-dopa induced the largest increase of DA levels in the striatum, while administration of dl-5-HTP produced the largest increase of 5-HT levels in the hypothalamus. These results suggest that the distribution of newly synthesized 5-HT or DA after the administration of 5-HTP or dopa, respectively, depends not only on that of aromatic l-amino acid decarboxylase, but also on that of nerve cells which selectively take up 5-HTP or dopa or that of synaptic vesicles which selectively take up 5-HT or DA. 3) The large doses of 5-HTP administration to 5,7-DHT pretreated rats induced the largest increase of 5-HT levels in the striatum. Thus, results in the present study indicate that the distribution of DA or 5-HT after the administration of dopa or 5-HTP, respectively, depends on the doses of dopa or 5-HTP given as well as the presence or absence of the lesioned 5-HT or DA neurons.     

Effects of 5-hydroxytryptophane on self-stimulation in rats

The effect of 5-hydroxytryptophane (5-HTP) was investigated on self-stimulation behavior in rats and orrelated with that on the contents of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in different areas of their brain. 5-HTP (28, 57 and 115 mg/kg, i.p.) caused a dose-dependent decrease (32, 57 and 66%, respectively) in self-stimulation responding, whereas other amino acids (e.g. glycine, glutamic acid) or the vehicle had negligible effects. Concomitant with the decrease in responding, there was a significant increase in 5-HT contents of the various areas of the brain in the treated rats; the NE contents showed only a slight decrease. 5-HTP continued to decrease self-stimulation responding, in spite of pretreatment with a decarboxylase inhibitor, RO4-4602 that reduced increase in 5-HT contents of peripheral organs (e.g. heart). Brain 5-HT appears to have an inhibitory role in this behavior.     

Plasma accumulation of metabolism of orally administered single dose L-5-hydroxytryptophan in man

Single oral doses of L-5-hydroxytryptophan (5-HTP) were administered in combination with L-aromatic amino acid decarboxylase inhibitors. The time courses of plasma concentrations of 5-HTP, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) and the concentrations of 5-HT in blood platelets were measured. Carbidopa enhanced the rise in plasma concentrations of 5-HTP 5-15 fold and counteracted the increase in plasma 5-HIAA levels induced by 5-HTP alone. A single dose of the decarboxylase inhibitor was equipotent to 14 days' pretreatment. Plasma or platelet concentrations of 5-HT failed to reflect the metabolism of 5-HTP. The ratio of 5-HTP to carbidopa influenced the systemic bioavailability of single dose administered 5-HTP indicating dose dependent absorption kinetics. Co-administration of L-dopa with 5-HTP and decarboxylase inhibitors had no effect on gastrointestinal absorption of 5-HTP in six parkinsonian patients.     

p,p′-DDT-Induced Myoclonus in Mice: The Effect of Enhanced 5-HT Neurotransmission

The acute behavioural consequences of intragastric p,p′-DDT in high doses to mice are stimulus sensitive abrupt muscle jerks (myoclonus). The serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP) ameliorated in contrast to the natural precursor tryptophan, the neurotoxin-induced myoclonus. The extracerebral decarboxylase inhibitor carbidopa and the selective 5-HT reuptake inhibitor paroxetine both enhanced the antimyoclonic action of 5-HTP. The effect was reversed by the 5-HT receptor blockers cinanserine and methysergide. The data add further evidence to a central serotonergic mechanism involved in p,p′-DDT induced myoclonus.     

Development of tolerance to the wet-dog shake behaviour but not the increase in seizure threshold induced by l-5-hydroxytryptophan during continued treatment in rats

The time course of different pharmacological effects of l-5-hydroxytryptophan (5-HTP) during continued treatment was studied in rats. 5-HTP was administered three times daily at 100 mg/kg IP in combination with the peripheral decarboxylase inhibitor carbidopa (10 mg/kg) for 14 days. 5-HTP induced a pronounced increase of the threshold for maximal electroconvulsions, decreased body temperature and body weight and induced characteristic wet-dog shake behaviour. Whereas the anticonvulsant effect increased during the 14 days of treatment, tolerance developed to the excitatory and, less rapidly, to the hypothermic and anorexigenic effects of 5-HTP. Biochemical determinations showed marked increases in 5-HTP and its metabolites, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid, in both plasma and brain throughout the period of treatment. The mechanisms underlying the different time-courses of the functional effects of 5-HTP during continued treatment are not clear, but effects on catecholaminergic systems as well as regional differences in 5-HT increases in the brain might be involved.     

Effects of amitriptyline and isocarboxazid on 5-hydroxytryptophan induced head twitches in mice

Effects of amitriptyline and isocarboxazid on brain 5-HT and 5-HIAA were examined in relation to their action on 5-HTP induced head twitches. Amitriptyline reduced 5-HTP induced head twitches but isocarboxazid increased them. Both amitriptyline and isocarboxazid caused a significant increase of brain 5-HT concentration in 5-HTP treated mice. Amitriptyline also caused a significant increase of 5-HIAA concentration, while isocarboxazid reduced 5-HIAA concentration in the brains of 5-HTP treated mice. Probenecid, which significantly increased 5-HIAA concentration without affecting brain 5-HT concentration in 5-HTP treated mice, reduced 5-HTP induced head twitches. These results suggest that 5-HTP induced head twitches might be induced by an increase of 5-HT concentration, and reduced by an increase of 5-HIAA or a decrease of 5-HT concentration in the brains of mice.     

Some 5-hydroxytryptamine-like actions of fenfluramine: a comparison with (+)-amphetamine and diethylpropion

The 5-hydroxytryptamine (5-HT)-like effects of fenfluramine have been investigated in mice in two different experiments. In a behavioural test in mice pretreated with tranylcypromine, fenfluramine caused stereotyped changes which were similar to those produced by 5-hydroxytryptophan (5-HTP) and were antagonized by methysergide or pretreatment with p-chlorophenylalanine (PCPA). Like 5-HTP, fenfluramine reduced the conditioned response in a one-trial conditioning test, an effect antagonized by methysergide or by PCPA pretreatment. The reduction in the conditioned response caused by a maximal electroconvulsion was also antagonized by PCPA, an effect prevented by 5-HTP. Equivalent anorectic doses of (+)-amphetamine and diethylpropion caused a small increase in stereotyped behaviour, but this was not modified by methysergide; both anorectic drugs were inactive in the one-trial conditioning test. It seems probable that the observed actions of fenfluramine are caused indirectly through the release of endogenous brain 5-HT.     

Morinda officinalis oligosaccharides increase serotonin in the brain and ameliorate depression via promoting 5-hydroxytryptophan production in the gut microbiota

Morinda officinalis oligosaccharides (MOO) are an oral drug approved in China for the treatment of depression in China. However, MOO is hardly absorbed so that their anti-depressant mechanism has not been elucidated. Here, we show that oral MOO acted on tryptophan → 5-hydroxytryptophan (5-HTP) → serotonin (5-HT) metabolic pathway in the gut microbiota. MOO could increase tryptophan hydroxylase levels in the gut microbiota which accelerated 5-HTP production from tryptophan; meanwhile, MOO inhibited 5-hydroxytryptophan decarboxylase activity, thus reduced 5-HT generation, and accumulated 5-HTP. The raised 5-HTP from the gut microbiota was absorbed to the blood, and then passed across the blood–brain barrier to improve 5-HT levels in the brain. Additionally, pentasaccharide, as one of the main components in MOO, exerted the significant anti-depressant effect through a mechanism identical to that of MOO. This study reveals for the first time that MOO can alleviate depression via increasing 5-HTP in the gut microbiota.     

Effect of phototherapy on the urinary excretion of tryptophan metabolites in neonatal hyperbilirubinemia.

The 24 hours urinary excretion of tryptophan metabolites after an aminoacid loading (50 mg/Kg body-weight) was studied in a group of hyperbilirubinemic infants with or without light exposure treatment, in comparison to normal newborn babies. Kynurenine was the main metabolite in the urine of the control subjects. In the hyperbilirubinemic infants a high urinary excretion of kynurenine and 3-hydroxyanthranilic acid was observed. In the ones treated with phototherapy these two substances were markedly decreased. Besides 3-hydroxykynurenine was almost always absent. The effect of the light exposure was studied on kynurenine and 3-hydroxykynurenine "in vitro". Kynurenine did not present any photodecomposition. On the contrary, 3-hydroxykynurenine was easily decomposed. This fact can explain the decreased excretion of 3-hydroxykynurenine and 3-hydroxyanthranilic acid observed in urine of hyperbilirubinemic newborn infants treated with phototherapy. The decrease of kynurenine in these infants probably is a consequence of the photodecomposition of 3-hydroxykynurenine.