Changes in urinary monoamine excretion in hyperkinetic children.

The pathogenetic mechanisms of hyperkinetic syndrome are not clear and need further investigation. The aim of the study was to find certain features of monoamine metabolism that are characteristic of children with hyperkinetic syndrome (HKS) with special regard to different degrees of severity (i.e. mild HKS and severe HKS ). The levels of L-dopa, dopamine, noradrenaline, adrenaline, homovanillic, vanillylmandelic and 5-hydroxyindoleacetic acids were measured in daily urine of children (7-11 years old) with mild and severe HKS using fluorimetric and chromatographic methods. Severe HKS was characterized by a significant increase of L-dopa (by 186%), dopamine (by 201%) and adrenaline (by 160%) excretion but an unchanged excretion of noradrenaline compared with those with mild HKS. The study revealed principle differences in monoamine metabolism between the mild and severe forms of HKS which may be of importance in deciding different pharmacotherapeutic approaches to use in patients with HKS of differing severity.

Dopamine-norepinephrine interaction in hyperactive boys treated with d-amphetamine.

We studied the relationship between the excretion of 3-methoxy-4-hydroxyphenylglycol, the main metabolite of central nervous system norepinephrine, and homovanillic acid, the main metabolite of dopamine, in 16 hyperactive boys and ten controls who were admitted to a clinical research center. We further examined the effect of d-amphetamine (0.5 mg/kg body weight daily for two weeks) on that relationship. The correlation coefficients r between MHPG and HVA excretion were significantly negative in hyperactive boys and significantly positive in controls when the relational effects of age, body surface, and 24-hour urinary creatinine with MHPG and HVA excretion were removed. Furthermore, the correlation coefficient r in hyperactive boys and in responders at baseline differed significantly from the correlation coefficients in post-treatment and in controls. The post-treatment correlation coefficient in hyperactive boys and responders did not differ from that in controls. We suggest an altered relationship between DA and NE activity in hyperactive children. Meaningful interpretation of the data should await the availability of more information on the amount of contribution of central NE and DA metabolism to urinary MHPG and HVA in both hyperactive and normal children.

[Catecholamine metabolism in Huntington's chorea (in patients and their phenotypically healthy relatives)]. / Obmen kateckholaminov pri khoree Gentingtona (u bol'nykh i ikh fenotipicheski zdorovykh rodstvennikov).

Excretion of free catecholamines and dopamine was examined in 18 patients with Huntington's chorea and in their phenotypically healthy relatives (16 persons). A relationship between the level of the dopamine excretion and the degree of the hyperkinetic disturbances has been revealed. Part of the healthy relatives showed a substantial increase in dopamine excretion. It is suggested that dopamine metabolism disturbances play the leading role in the disease development, and that it would be wise to use therapeutic agents acting upon the striatum small cells and dopaminergic receptors.

Patterns of peptides and protein-associated-peptide complexes in psychiatric disorders.

Peptidic neurones may be considered as multisignal intergrators and transducers. When formation or release of peptide outstrips genetically determined breakdown capacity, overflow of peptides to the body fluids and urine may be expected. In this paper, pathological urinary chromatographic patterns of peptides are shown for genetic, functional and mixed disorders. Part symptoms of the disorders may be induced with the biologically isolated and purified peptides as well as with chemically synthesized peptides.

Norepinephrine metabolism and clinical response to dextroamphetamine in hyperactive boys.

The 24-hour urinary catecholamine metabolites 3-methoxy-4-hydroxyphenylglycol, normetanephrine, and metanephrine were measured in 23 hyperactive boys and 13 matched healthy controls. The hyperactive children excreted lower MHPG and higher NM (low MHPG/NM ratio) amounts than in controls. The administration of d-amphetamine in the dose of 0.5 mg/kg body weight divided over two doses daily for two weeks decreased MHPG excretion in the hyperactive children. When the hyperactive children group was divided into drug responders and nonresponders according to their pre- and post-treatment scores on the Conners Teacher Questionnaire, d-amphetamine administration decreased MHPG excretion in the responders and did not change it in the nonresponders. Percent decrease in MHPG excretion correlated significantly with percent change in the hyperactivity factor of the questionnaire on the Spearman Rank Order Correlation Coefficient. Pretreatment urinary metabolites did not differentiate the responders from nonresponders. It is suggested that a relationship between CNS norepinephrine metabolism and hyperactivity exists and that d-amphetamine may achieve its therapeutic action in hyperactive children by altering CNS NE metabolism.

Urinary MHPG excretion in minimal brain dysfunction and its modification by d-amphetamine.

The authors studied the excretion of 3-methoxy-4-hydroxyphenlyglycol (MHPG) in 15 hyperactive boys and 13 controls. They further examined soft neurologic signs and clinical drug response to d-amphetamine administration for two weeks in the hyperactive boys. MHPG excretion was significantly lower in the hyperactive boys than in the controls. d-Amphetamine decreased MHPG excretion significantly in the drug responders only. Pretreatment MHPG excretion did not predict clinical drug response. The responders had more soft neurologic signs than the nonresponders. Furthermore, soft neurologic signs were not related to pretreatment MHPG levels.

[Pathogenesis of hyperkinesis in children]. / O patogeneze giperkinezov u detei.

Pheylalanine metabolism was studied in 56 children with various forms of hyperkinesias. It was found that in the development of slow and fast hyperkinesias a certain role belongs to dihydroxyphenylalanine (DOPA). It is probable, that in patients with Turett's syndrome the synthesis of DOPA is increased while in patients the excretion of phenylacetylglutamine was found to be disturbed: it was decreased in the patients with the fast and increased in the children with the slow hyperkinesias. Phenylalanine load led to a lowering of the DOPA level in the patients with Turett's syndrome; an intensification of the synthesis of phenylacetylglutamine and diminution of the intensity of hyperkinesias. L-glutamine load resulted in detoxication of the toxic phenylalanine metabolites which inhibited the DOPA synthesis, as well as in a short-time increase in the phenylacetylglutamine excretion and a moderation of tonic hyperkinesias that manifested by athetosis and dystonia. All this points out that in the development of various forms of hyperkinesias a certain role belongs to amino acid metabolites.

Urinary catecholamines and amphetamine excretion in hyperactive and normal boys.

Urinary catecholamines and metabolites and urinary amphetamine excretion were examined for hyperactive and normal boys following a single dose of dextroamphetamine (0.5 mg/kg) and placebo. Hyperactive children showed a significantly faster rate of excretion of amphetamine which could not be accounted for by previous exposure to drug or by signs of neurological involvement. Urinary norepinephrine (NE) was significantly higher for hyperactive than for normal children, but NE excretion did not correlate with motor activity or any measures of arousal. The single dose of amphetamine produced a significant rise in urinary epinephrine excretion (EP) for the normal children but not for the hyperactive group, supporting the notion of a more sluggish catecholamine response to stimulants for hyperkinetic children.

The hyperkinetic child syndrome and brain monoamines: pharmacology and therapeutic implications.

Decreased catecholaminergic activity within the central nervous system has been associated with altered arousal, attention, learning, and kinetic function in animals and humans. The hyperkinetic child syndrome (HCS) involves dysfunction in all these spheres and may thus reflect diminished catecholamine activity, particularly as related to brain dopamine. Accordingly, the efficacy of catecholaminergic agents in treating the HCS is a predictable rather than a paradoxical effect of these agents. Sufficient evidence is now available to strongly implicate catecholamine hypoactivity in the pathopharmacology of the HCS.

Lead and hyperactivity: lead levels among hyperactive children.

Previous work has demonstrated an association between hyperactivity and increased body lead burdens in school-age children. In the present study it is shown that within a group of hyperactive children those for whom an organic etiology is present have lead burdens lower than in those for whom no apparent cause could be found. These data lead us to reject the notion that hyperactivity per se is responsible for the acquisition of elevated lead levels, and further strengthen the suspicion that for some children lower lead level absorption may be implicated in the development of the hyperkinetic disorder.

Urinary catecholamine metabolites in hyperkinetic boys treated with d-amphetamine.

The authors studied the excretion of 3-methoxy-4-hydroxyphenyl glycol (MHPG), normetanephrine (NM), metanephrine, and homovanillic acid in 7 hyperactive and 12 control children. MHPG was lower but NM was significantly higher in hyperactive children than in controls. Administration of d-amphetamine for 2 weeks depressed the levels of MHPG, NM, and metanephrine. The authors suggest a decreased central norepinephrine activity, which may be secondary to the interruption of norepinephrine fibers in the medial forebrain bundle.

A reproducible gas chromatographic mass spectrometric assay for low levels of methylphenidate and ritalinic acid in blood and urine.

A rapid, sensitive method of analysis for methylphenidate and ritalinic acid in blood and urine has been developed using gas chromatography mass spectrometry and selected ion monitoring for separation and detection. The methylphenidate is isolated by solvent extraction into chloroform and the ritalinic acid is isolated by salting out into isopropyl alcohol, followed by methylation and subsequent solvent extraction. The method has been applied to the study of methylphenidate metabolism and excretion in adults and hyperactive children undergoing treatment with methylphenidate.