Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of p-CPA and 5-HTP followed by p-CPA on sleep was studied in rats with olfactory bulb lesions (O.B. lesioned rats). In these rats, electrodes were chronically implanted to record the EEG (frontal cortex and dorsal hippocampus), the cervical electromyogram and eye movements. The REM sleep stage was selectively decreased from 24 to 32 hours after 200 mg/kg of p-CPA in the sham lesioned rats, whereas both the slow wave sleep and REM sleep stages were markedly decreased by the same dose of p-CPA in the O.B. lesioned rats. In both sham and O.B. lesioned groups, the slow wave sleep and REM sleep stages decreased from 24 to 32 hours after 400 mg/kg of p-CPA and the percentage of decrease in the slow wave sleep stage was much larger with 400 mg/kg of p-CPA than with 200 mg/kg and 400 mg/kg of p-CPA. In the O.B. lesioned rats, the insomnia produced by 200 mg/kg and 400 mg/kg of p-CPA disappeared with 5-HTP (5 mg/kg). On the other hand, the insomnia produced by 200 mg/kg of p-CPA did not recur with 5-HTP in the sham lesioned rats, but with 400 mg/kg there was a recurrence. These results suggest that the enhanced effect of p-CPA and 5-HTP followed by p-CPA in the O.B. lesioned rats is due to changes in the sensitivity of the serotonergic system in the brain.
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PMID:Effects of p-chlorophenylalanine (p-CPA) on sleep in olfactory bulb lesioned rats. 19 73

In the rat, the insomnia which follows the administration of parachlorophenylalanine (p-CPA), a serotonin synthesis inhibitor, is transiently reversed either by intra-cisternal injection of L-5-HTP or by an associated injection of 5-HTP and an L-aromatic-acid-decarboxylase inhibitor (benserazide). Histochemical, immunohistochemical and chemical investigations showed that 5-HTP administration does not lead to a detectable increase in cerebral 5-HT. These findings suggest that the restoration of sleep after p-CPA treatment could be mediated by the central action of 5-HTP.
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PMID:The role of 5-hydroxytryptophan (5-HTP) in the regulation of the sleep/wake cycle in parachlorophenylalanine (p-CPA) pretreated rat: a multiple approach study. 183 62

Para-chlorophenylalanine, a blocker of serotonin biosynthesis by inhibiting tryptophan hydroxylase, induced total insomnia which was accompanied in cat by a permanent discharge of ponto-geniculo-occipital activity. L-5-Hydroxytryptophan microinjection (1-4 micrograms/0.5 microliters) in the anterior hypothalamus 72 h after para-chlorophenylalanine administration, restored both slow wave sleep and paradoxical sleep with variable latencies for each state of sleep. On the contrary, ponto-geniculo-occipital activity was never suppressed. The hypnogenic effects of L-5-hydroxytryptophan were always followed by a return of the para-chlorophenylalanine-induced insomnia. On the other hand, the temperature recording did not show any alteration of the cerebral temperature after para-chlorophenylalanine treatment but the subsequent L-5-hydroxytryptophan microinjection was followed by hyperthermia. Using immunohistochemistry for serotonin after intrahypothalamic L-5-hydroxytryptophan microinjection in parachlorophenylalanine-pretreated cat, we defined a restricted region of the anterior hypothalamus possibly responsible for the hypnogenic effect. This region included the lateral hypothalamus and the anterior hypothalamic area. It is suggested that the reversible hypersomnia after L-5-hydroxytryptophan microinjection in the anterior hypothalamus in para-chlorophenylalanine-pretreated cat is due to a neurohormonal action of serotonin: serotonin could act upon the anterior hypothalamus which secondarily inhibits a waking system located in the ventrolateral hypothalamus leading to the appearance of paradoxical sleep.
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PMID:Reversibility of para-chlorophenylalanine-induced insomnia by intrahypothalamic microinjection of L-5-hydroxytryptophan. 252 39

A pharmacological study was carried out of a case of severe insomnia following brain-stem lesions; several polygraphic controls were used. Initially total duration of sleep was brief (less than 4 h) with a high REM/NREM ratio and a short paradoxical sleep (PS) latency. In addition, periodic breathing and tremor were observed. Slow injection of delta-sleep-inducing peptide (DSIP) improved sleep both quantitatively and qualitatively, although PS latency remained short. These effects were reversible. The effects of 5-HTP + benzerazide, of L-DOPA + benzerazide (Modopar) and of clonazepam (Rivotril) were compared.
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PMID:Sleep disturbances in a case of brain-stem lesions; pharmacological study. 619 41

In adult rats an anterodorsal bilateral hippocampectomy produced an increase in motor activity without modification of the amount of the different sleep stages. In hippocampectomized rats p-chlorophenylalanine produced an insomnia which can be reversed by 5-HTP. These results show that the insomnia produced by brain serotonin depletion is not a result of the hyperactivity produced by the treatments which cause such depletion.
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PMID:Effects of serotonin synthesis inhibition on sleep in hippocampectomized rats. 621 96

In p-chlorophenylalanine (PCPA) pretreated insomniac cats, the intraventricular (i.v.t.) injection of artificial cerebrospinal fluid (CSF) did not impair the insomnia. CSF transfer from normal cats was followed in 4 out of 9 cats by the restoration of paradoxical sleep (PS). However, CSF transfer from paradoxical sleep deprived cats did result in 12 out of 13 experiments in a significant increase in slow wave sleep (SWS) and the induction of PS. Biochemical analysis of the CSF from normal or PS deprived cat has shown that the highest quantity of indolamines was at least 1000 times smaller than the threshold dose of 5-HTP (200 microgram) which has been shown to be able to restore sleep by i.v.t. injection in PCPA pretreated insomniac cats. These experiments provide evidence that the transfer of a small quantity of CSF (250 microliter) from a previously paradoxical sleep deprived cat can restore paradoxical sleep in an insomniac PCPA pretreated cat in bypassing the biosynthesis of serotonin (5-HT). These results suggest that a 'paradoxical sleep inducing factor' may be stored in the central nervous system during sleep deprivation.
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PMID:Restoration of paradoxical sleep by cerebrospinal fluid transfer to PCPA pretreated insomniac cats. 621 42

5-Hydroxytryptophan (5-HTP) is the intermediate metabolite of the essential amino acid L-tryptophan (LT) in the biosynthesis of serotonin. Intestinal absorption of 5-HTP does not require the presence of a transport molecule, and is not affected by the presence of other amino acids; therefore it may be taken with meals without reducing its effectiveness. Unlike LT, 5-HTP cannot be shunted into niacin or protein production. Therapeutic use of 5-HTP bypasses the conversion of LT into 5-HTP by the enzyme tryptophan hydroxylase, which is the rate-limiting step in the synthesis of serotonin. 5-HTP is well absorbed from an oral dose, with about 70 percent ending up in the bloodstream. It easily crosses the blood-brain barrier and effectively increases central nervous system (CNS) synthesis of serotonin. In the CNS, serotonin levels have been implicated in the regulation of sleep, depression, anxiety, aggression, appetite, temperature, sexual behaviour, and pain sensation. Therapeutic administration of 5-HTP has been shown to be effective in treating a wide variety of conditions, including depression, fibromyalgia, binge eating associated with obesity, chronic headaches, and insomnia.
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PMID:5-Hydroxytryptophan: a clinically-effective serotonin precursor. 972 88

Semen Zizhiphi Spinozae has been used extensively for the treatment of insomnia. This study investigated the effect and possible mechanism of action of spinosin (also known as 2''-beta-o-glucopyranosyl swertisin), a major constituent of semen Zizhiphi Spinozae, on sleep in mice. The present results showed that spinosin significantly and dose-dependently augmented pentobarbital (45 mg/kg, i.p.)-induced sleep, reflected by increased sleep time and reduced sleep latency assessed with the loss-of-righting reflex, and these effects were potentiated by the 5-hydroxytryptamine (serotonin) precursor 5-hydroxytryptophan (5-HTP, 2.5 mg/kg,i.p.). With a subhypnotic dose of pentobarbital (28 mg/kg, i.p.), spinosin significantly increased the rate of sleep onset and exhibited a synergistic effect with 5-HTP (2.5 mg/kg, i.p.). Pretreatment with p-chlorophenylalanine (PCPA, 300 mg/kg, s.c.), an inhibitor of tryptophan hydroxylase, significantly decreased pentobarbital-induced sleep time, and spinosin significantly reversed this effect. The dopamine precursor L-3-(3, 4-dihydroxyphenylalanine (L-DOPA) reduced pentobarbital-induced sleep, an effect not significantly affected by spinosin. These results suggest that spinosin potentiated pentobarbital-induced sleep via a serotonergic mechanism.
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PMID:Spinosin, a C-glycoside flavonoid from semen Zizhiphi Spinozae, potentiated pentobarbital-induced sleep via the serotonergic system. 1846 60

The use of complementary alternative medicine (CAM) in paediatric populations is considerably increased, especially for pain and chronic conditions, as demonstrated by epidemiological surveys both in Europe and in the USA. In our study, CAM was used in 76 % patients of a cohort of 124 children affected by headache (age 4-16 years; 67 % female; 70 % migraine without aura, 12 % migraine with aura, 18 % tensive headache according to IHS criteria) consecutively recruited at a Pediatric Headache University Center. CAM was used as preventive treatment in 80 % cases. The main reasons for seeking CAM were: the wish of avoiding chronic use of drugs with their related side effects, the desire of an integrated approach, the reported inefficacy of conventional medicine, and a more suitable children disposition to CAM than to pharmacological compound. Female gender, younger age, migraine without aura, parents' higher educational status, maternal use of CAM and other associated chronic conditions, correlated with CAM use (p < 0.05). 73 % patients chose CAM also to treat other diseases (i.e. allergies, colitis, asthma, insomnia, muscle-scheletric disorders and dysmenorrhoea). The most assumed CAM were: herbal remedies (64 %) such as Valeriana, Ginkgo biloba, Boswellia serrata, Vitex agnus-castus, passion flower, Linden tree; vitamins/minerals supplements (40 %) with magnesium, 5-Hydroxytryptophan, vitamin B6 or B12, Multivitamin compounds; Homeopathy (47 %) with Silicea, Ignatia Amara, Pulsatilla, Aconitum, Nux Vomica, Calcarea phosphorica; physical treatment (45 %) such as Ayurvedic massage, shiatsu, osteopathy; yoga (33 %); acupuncture (11 %). CAM-often integrated with conventional care-was auto-prescribed in 30 % of the cases, suggested by non-physician in 22 %, by the General Practitioner in 24 % and by paediatrician in 24 %. Both general practitioners and neurologists were mostly unaware of their patients' CAM use. In conclusion, neurologists should inquire for CAM use and be prepared to learn about CAM therapies or to directly interact with CAM trained experts, in order to coordinate an integrative approach to health, as especially required in paediatric headache patients and their parents. Further studies are required to investigate safety and efficacy of CAM in pediatric headache, as a possible side-medicine to conventional pharmacological approach.
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PMID:Complementary and alternative medicine (CAM) use in an Italian cohort of pediatric headache patients: the tip of the iceberg. 2486 52

5-Hydroxytryptophan (5-HTP) is a drug that is clinically effective against depression, insomnia, obesity, chronic headaches, etc. It is only commercially produced by the extraction from the seeds of Griffonia simplicifolia because of a lack of synthetic methods. Here, we report the efficient microbial production of 5-HTP via combinatorial protein and metabolic engineering approaches. First, we reconstituted and screened prokaryotic phenylalanine 4-hydroxylase activity in Escherichia coli. Then, sequence- and structure-based protein engineering dramatically shifted its substrate preference, allowing for efficient conversion of tryptophan to 5-HTP. Importantly, E. coli endogenous tetrahydromonapterin (MH4) could be utilized as the coenzyme, when a foreign MH4 recycling mechanism was introduced. Whole-cell bioconversion allowed the high-level production of 5-HTP (1.1-1.2 g/L) from tryptophan in shake flasks. On this basis, metabolic engineering efforts were further made to achieve the de novo 5-HTP biosynthesis from glucose. This work not only holds great scale-up potential but also demonstrates a strategy for expanding the native metabolism of microorganisms.
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PMID:Engineering bacterial phenylalanine 4-hydroxylase for microbial synthesis of human neurotransmitter precursor 5-hydroxytryptophan. 2493 77


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