Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. PE is present in the brain in tiny quantities; it is heterogeneously distributed and present in synaptosomes. 2. It is synthesised from phenylalanine by L-AADC and oxidatively deaminated by MAO-B. Its turnover is remarkably fast. 3. Its concentration, particularly in the caudate nucleus, is affected by MAO inhibition (increased), lesion of the Substantia nigra (decreased), amine depletion (increased) and antipsychotic drugs (increased). 4. When iontophoresed (or injected) it amplifies the effects of DA and NA (and their agonists) but is without effect on other neurotransmitters. 5. It is suggested that it acts postsynaptically as a neuromodulator of catecholaminergic neurotransmission and that it is involved in the mechanism of action of Deprenyl; it is also suggested that it, or its principal metabolite PAA, may be involved in the aetiology of schizophrenia, depression and aggression as well as perhaps in other neuropsychiatric conditions.
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PMID:Phenylethylaminergic modulation of catecholaminergic neurotransmission. 165 28

Plasma samples were collected from 41 patients who met DSM-III criteria for schizophrenia and from 34 healthy controls. Phenylethylamine (PE) levels were determined using a gas chromatography-mass spectrometry negative chemical ionization method. PE was significantly higher in the schizophrenic patients compared with controls. There were no differences in PE between paranoid and nonparanoid patients. Plasma PE did not appear to be influenced by the severity of schizophrenic symptoms (rated by BPRS, SANS, and SAPS) or by the amount of dietary phenylalanine ingested within 24 hr of testing. Plasma PE did not correlate with current or past exposure to neuroleptic medication. It was not possible, however, to test individual patients during two periods when they were taking and not taking medication. Thus it is possible that neuroleptic exposure may have confounded the results. This study provides further evidence that PE excess may play a role in the etiology of schizophrenia but does not support previous studies which suggest that such an abnormality is limited to the paranoid subgroup.
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PMID:Plasma phenylethylamine in schizophrenic patients. 191 6

Basal serum amino acids (including central monoamine precursors), central monoamines, and hormones were studied in schizophrenic patients (drug-naive; n = 20; drug-withdrawn for 3 or more days, n = 67; neuroleptic-treated, n = 23) and healthy subjects (n = 90) to answer the following questions: (1) Do neuroleptic-withdrawn and neuroleptic-naive patients differ on these serum measures? (2) What are the effects of neuroleptic treatment on these measures? (3) On which variables do drug-free and neuroleptic-treated patients differ? Because serum amino acid, central monoamine, and hormone levels were similar in drug-naive and drug-withdrawn patients, data from these groups ("drug-free") were combined and compared to those of healthy subjects and neuroleptic-treated patients. Asparagine, citrulline, phenylalanine, and cysteine were higher, while tyrosine, tryptophan, and the ratio of tryptophan to competing amino acids were significantly lower in drug-free schizophrenic patients than in healthy subjects. Dopamine was increased, and melatonin and thyroid hormones were decreased in drug-free schizophrenic patients compared to healthy subjects. Norepinephrine, epinephrine, and prolactin were higher in neuroleptic-treated men compared to drug-free male patients or healthy men. These results are consistent with the hypothesis of dopaminergic overactivity in schizophrenia, which might be caused by altered amino acid precursor availability and could be related to the decrease in melatonin and reduction in thyroid hormone levels.
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PMID:Serum amino acids, central monoamines, and hormones in drug-naive, drug-free, and neuroleptic-treated schizophrenic patients and healthy subjects. 198 23

Compared to healthy controls, unmedicated schizophrenic patients had significantly higher plasma concentrations of taurine, methionine, valine, isoleucine, leucine, phenylalanine, and lysine. Except for taurine, these amino acids share the L-transport system for neutral amino acids. In the patients, homovanillic (HVA) acid levels in CSF were decreased and the plasma levels of the amino acids competing with tyrosine and tryptophan for transport into the brain, were all negatively correlated to the CSF concentrations of HVA and 5-HIAA. These findings could be explained by a change in the affinity of the L-system or by a decrease in its overall capacity in schizophrenia. Raised plasma levels of the competing amino acids may limit the brain uptake of tyrosine, leading to a diminished dopamine turnover, and resulting in a compensatory development of supersensitive dopamine receptors.
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PMID:Plasma amino acids in relation to cerebrospinal fluid monoamine metabolites in schizophrenic patients and healthy controls. 241 98

1. Propranolol has been reported to be beneficial in treating patients suffering from a variety of diseases including migraine, psychosis and schizophrenia. The mode of action of propranolol in the treatment of the above diseases is not clear. 2. An investigation into the possible effect of propranolol on receptor activated inositol phospholipid hydrolysis was carried out using human neutrophils. Receptor activated inositol phosphate production by formyl-methionyl-leucyl-phenylalanine has also been studied. 3. DL-propranolol caused a time and concentration dependent increase in inositol phosphate generation which was similar to that obtained for chemotactic peptide in neutrophils. The EC50 for propranolol was 2 microM compared to 0.5 microM for chemotactic peptide. 4. These results indicate the possibility that propranolol has a direct action on inositol phospholipid hydrolysis in addition to its beta-blocking effect.
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PMID:Stimulation of inositol phosphate production by propranolol in human neutrophils. 322 51

Amino acid transport was studied in vitro in cultured fibroblasts from schizophrenic patients and controls. An isolated decrease in the transport capacity (Vmax) for tyrosine was observed in cells from the patients. The Km for tyrosine transport was unaffected. The kinetic parameters for phenylalanine, tryptophan, leucine and glycine transport did not differ between patients and controls. Competitive inhibition among the amino acids transported by the L-system and its exchange properties were normal in cells from the patients. No differences in intracellular levels of amino acids between patients and controls were observed. The decreased tyrosine transport in the cells from schizophrenic patients appears not to be related to any known amino acid transport system and may reflect a more general defect in plasma membrane function in schizophrenia.
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PMID:Decreased tyrosine transport in fibroblasts from schizophrenic patients. 369 4

A number of compounds have been shown to inhibit the degradation of enkephalins. As expected, these compounds produce naloxone reversible analgesia and potentiate the analgesia produced by enkephalins and by acupuncture. One of these, D-phenylalanine, is also anti-inflammatory. D-phenylalanine has proven to be beneficial in many human patients with chronic, intractable pain. It is proposed the enkephalinase inhibitors may be effective in a number of human "endorphin deficiency diseases" such as depression, schizophrenia, convulsive disorders and arthritis. Such compounds may alleviate other conditions associated with decreased endorphin levels such as opiate withdrawal symptoms.
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PMID:D-phenylalanine and other enkephalinase inhibitors as pharmacological agents: implications for some important therapeutic application. 612 72

Urinary phenylacetic acid (PAA) excretion was found to be decreased in a group of chronic schizophrenic patients, particularly in a nonparanoid subtype. No significant change in PAA excretion was observed in a group of 21 unipolar depressed patients. Urinary PAA was studied following the administration of phenylethylamine, monoamine oxidase inhibitors, a dopa decarboxylase inhibitor, a low phenylalanine diet, and phenylalanine loads in several groups of psychiatric patients and normal volunteers. While Phenylethylamine ingestion increased urine PAA, inhibition of both phenylethylamine metabolism and synthesis failed to alter urine PAA. These studies suggest that urine PAA is primarily derived from phenylalanine transamination or pathways not involving monoamine oxidase or both. The observed decrease in PAA excretion in some schizophrenic patients may reflect an alteration in this pathway. The high phenylethylamine excretion previously reported in some chronic schizophrenic patients is not directly related to the observed low PAA excretion. Therefore measurement of urine PAA is not expected to be useful in assessing any phenylethylamine abnormalities in psychiatric disorders. The possible contribution of reduced phenylalanine transamination and its subsequent increased availability for the possible synthesis of phenylethylamine in schizophrenia is discussed.
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PMID:Phenylacetic acid excretion in schizophrenia and depression: the origins of PAA in man. 671 36

Rats administered intracerebroventricular (IVT) injections of 3-Carboxy-1,2,3,4-tetrahydroisoquinoline (I) or 6,7-Dihydroxy-1,2,3,4-tetrahydroisoquinoline (II), the condensation products of formaldehyde with phenylalanine and dopamine, respectively, were evaluated in the open field and shuttle box situation. In the open field, 45 min after the acute administration of I, several repetitive purposeless responses and other manifestations such as teeth chattering, wet dog shakes and stiffness of the tail were observed; however, no quantitative effects were detected in the behavioral parameters recorded. Further studies were performed utilizing the shuttle box situation with drugs I and II. They produced an increase in the number of escapes and latency of shocks when measured 45 min after IVT administration (10 mg/ml and 1 mg/ml, respectively; 20 microliters). Our data suggest that the studied compounds induce qualitative alterations as well as changes in shuttle avoidance behavior in the rat when measured 45 min after administered. The effects were found to be dose and time dependent, being reversible when measured 24 and 48 hours after administration of the drugs. The present results open the possibility that the in vivo formation of tetrahydroisoquinolines could be involved in some mental pathologies, such as schizophrenia, as has been previously suggested.
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PMID:Behavioral alterations induced by formaldehyde-derived tetrahydroisoquinolines. 724 42

In the present study, five allelic fragments were typed by a polymerase chain reaction (PCR) process with a pair of primers specific for the tetranucleotide (TCAT) repeat sequence in the first intron of the human tyrosine hydroxylase (TH) gene and their sizes (bp) were 114 (A), 118 (B), 122 (C), 126 (D) and 130 (E), respectively. The AE genotypic frequency was found to be significantly higher in unrelated patients with schizophrenia than in unrelated control subjects (chi 2 = 4.18, p < 0.05). ANOVA revealed a significant difference between the three groups (neuroleptic-free patients possessing or not possessing the AE genotype, and unrelated control subjects) in the concentration of serum noradrenaline (F = 4.96, df = 2.79, p < 0.01), but no significant differences were found between the three groups in the concentrations of serum homovanillic acid, phenylalanine and tyrosine. These results suggest that the polymorphic intron 1 of the human TH gene may be associated with disturbances of the catecholamine pathway in schizophrenia.
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PMID:Association of polymorphic VNTR region in the first intron of the human TH gene with disturbances of the catecholamine pathway in schizophrenia. 755 67


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