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

Parachlorophenylalanine (PCPA) produces a total insomnia with a permanent discharge of pontogeniculooccipital (PGO) activity. We studied the reversibility of this insomnia in physiological slow-wave sleep (SWS) and paradoxical sleep (PS) after 5-hydroxytryptophan (5HTP) and serotonin (5HT) administration. Whereas D-5HTP (5 mg/kg) had no effect, parenteral injection of L-5HTP (2.5 mg/kg) or DL-5HTP (5 mg/kg) immediately suppressed PGO activity, then gave rise to the return of SWS and PS with delays of 26 and 60 min, respectively. Intraventricular or intracisternal administration of 5HTP (250 to 1500 micrograms) or 5HT produced physiological sleep with variable delays. If chloramphenicol (which selectively suppresses PS in normal cat) is administered in a PCPA-pretreated cat, 5HTP still suppressed PGO activity and gave rise to a lower amount of SWS but did not restore PS. The results suggest that 5HTP is rapidly decarboxylated into 5HT in restoring the PGO gating effect. Thus, 5HT would seem to act as a classic neurotransmitter. The long latency for PS (and its suppression by chloramphenicol) suggests that 5HT would appear to be a neurohormone controlling another sleep-inducing factor.
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PMID:[Insomnia caused by administration of para-chlorophenylalanine: reversibility by peripheral or central injection of 5-hydroxytryptophan and serotonin]. 315 60

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

When injected intraperitoneally (i.p.) into normal cats, methiothepin (1-7.5 mg/kg) or metergoline (0.5-8 mg/kg) induced total insomnia. The duration of suppression of deep slow-wave sleep (SWS2) and paradoxical sleep (PS) was dose-related for methiothepin (10-30 h), but was shorter and not dose-related for metergoline (3-5 h). When injected into the fourth ventricle, methiothepin (20 microgram) induced a selective suppression of PS for 6-7 h). In rho-chlorophenyl-alanine (PCPA)-pretreated, insomniac cats, i.p. injection of 5 mg/kg of DL-5-hydroxytryptophan(5-HTP) was followed by SWS and PS after latencies of 25 and 62 min. When methiothepin (2.5 mg/kg) or metergoline (4 mg/kg) were given before 5-HTP, the latency for the first PS episode increased dramatically to 7 h. Thereafter PS occurred periodically for 10 h but no SWS appeared. These results suggest that a 'PS factor' induced by 5-HTP and different from indolamines is preserved during the antagonistic effect of methiothepin or metergoline until it can act upon the executive mechanisms of PS. Our data also suggest that metergoline and methiothepin suppress but do not delay the mechanism responsible for SWS2 in the PCPA-5-HTP paradigm.
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PMID:5-HT antagonists suppress sleep and delay its restoration after 5-HTP in p-chlorophenylalanine-pretreated cats. 621 54

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

Fibromyalgia syndrome is a musculoskeletal pain and fatigue disorder manifested by diffuse myalgia, localized areas of tenderness, fatigue, lowered pain thresholds, and nonrestorative sleep. Evidence from multiple sources support the concept of decreased flux through the serotonin pathway in fibromyalgia patients. Serotonin substrate supplementation, via L-tryptophan or 5-hydroxytryptophan (5-HTP), has been shown to improve symptoms of depression, anxiety, insomnia and somatic pains in a variety of patient cohorts. Identification of low serum tryptophan and serotonin levels may be a simple way to identify persons who will respond well to this approach.
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PMID:Fibromyalgia and the serotonin pathway. 980 12


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