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)

According to the hypothesis implying that the main mechanism underlying opiate addiction is the blockade by opiates of NMDA receptor functions and subsequent upregulation and supersensitivity of the receptors, noncompetitive NMDA receptor blocker dextromethorphan (DM) has been successfully used in the heroin addict treatment. As the stimulation of NMDA receptors modulates the release of neurotransmitters and hormones such as NE, D, ACh, GH, LH, LSH, ACTH etc., all of which have been found responsible for the manifestation of abstinence syndrome signs including craving and neuronal death by excessive stimulation of NMDA receptors, the incomplete blockade of the NMDA receptors minimizes the intensity of the abstinence syndrome and provides the downregulation of the receptors. In the present study, tizanidine (TIZ), which inhibits the release of endogenous excitatory aminoacids by the agonistic activity on alpha 2-adrenoreceptors, was combined with DM to obtain further benefits. Forty-four male and three female heroin addicts were the subjects of the study. Their daily mean heroin intake was about 2.28 g street heroin. The main duration of heroin use was approximately 3.4 years. Two to three hours after abrupt withdrawal, the outpatients were given 15 mg DM every hour, 25 or 50 mg chlorpromazine (CPZ) + 4 mg TIZ every six hours and 10 mg diazepam + 10 mg hyoscine N-butyl Br + 250 mg dipyrone every six hours three hours following CPZ. The addicts were controlled twice a day. Yawning, rhinorrhea, perspiration, piloerection, restlessness, insomnia, emesis, diarrhea, craving, rejection of smoking and pupils were observed and/or questioned. Two of the 47 outpatients took heroin on the first days.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The combination of tizanidine markedly improves the treatment with dextromethorphan of heroin addicted outpatients. 771 85

Pesticides are used extensively throughout the world in agriculture and in pest control as well as for community health purposes. Organophosphate (OP) pesticide self-poisoning is an important clinical problem in rural regions of the developing world that kills an estimated 200,000 people every year. Unintentional poisoning kills far fewer people but is an apparent problem in places where highly toxic OP pesticides are available. Neurologic dysfunction is the best documented health effect of pesticide exposure. High-level exposure has both acute and long-term neurologic signs and symptoms, and adverse effects have been reported in most type of pesticides, including organophosphate (OP), carbamate, organochlorine, and pyrethroid insecticides, herbicides, fungicides, and fumigants. Acute OP pesticide exposure can involve in wide range of both central and peripheral neurologic symptoms. Increased neurologic symptom prevalence may provide early evidence of neurologic dysfunctions, before clinically measurable signs are evident.In this study, we analyzed the cross-sectional data on neurologic signs and symptoms from 225 rural children, both males (n = 132) and females (n = 93) who were occupationally and paraoccupationally exposed to methyl OPs (dichlorvos, fenthion, malathion, methyl parathion) and ethyl OPs (chlorpyrifos, diazinon, ethyl parathion) as they belonged to agricultural families handling, mixing, and spraying the OP pesticides. The children completed a specially designed questionnaire (Q16) on neurologic symptoms associated with pesticide exposure with their parental help. A suitable reference group consisting of rural children (n = 50) never involved in pesticide handling (neither outdoor nor indoor) belonging to similar socioeconomic strata included in the study to compare the prevalence of various neurologic symptoms between the two groups.Among all the neurologic self-reported symptoms, headache, watering in eyes, and burning sensation in eye/face were the most important clinical manifestations attributed to OP pesticide exposure. These symptoms could probably be the consequence of chronic effects of most pesticides on the central nervous system. The muscarinic symptoms reported the maximum prevalence of salivation (18.22%), whereas lacrimation was observed in 17.33% cases, followed by diarrhea in 9.33% cases. The nicotinic clinical manifestations of acute OP poisoning revealed excessive sweating in 13.78% cases and tremors in 9.3% cases followed by mydriasis in 8.4% exposed children. The characteristic cholinergic symptoms, such as insomnia, headache, muscle cramps, weakness, and anorexia were also reported by both male and female exposed children. The high frequency of neurologic symptoms observed in the study may be due to parasympathetic hyperactivity due to the accumulated ACh resulting from AChE inhibition.
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PMID:A study of neurologic symptoms on exposure to organophosphate pesticides in the children of agricultural workers. 2112 82

Since the pioneering work of Gadea-Ciria (Gadea-Ciria M, Stadler H, Lloyd KG, Bartholini G. Acetylcholine release within the cat striatum during the sleep-wakefulness cycle. Nature 1973; 243:518-519) indicating pointing to the involvement of acetylcholine and basal ganglia in sleep regulation; extensive literature has suggested that this brain complex participates in the control of the sleep-waking cycle (SWC). On the other hand, it has been demonstrated that the endocannabinoid system (eCBS) is prominently involved in the regulation of the SWC, mood and its related disorders. Since cannabinoid receptor 1 (CB1R) is highly expressed in basal ganglia, in particular in the entopeduncular nucleus (EP), we believe that it is important to know what the role of the EP CB1R is on SWC, depression, and anxiety. To provide insight into the role of the EP CB1R in the regulation of wakefulness (W), non-rapid eye movement sleep (NREMs) and rapid eye movement sleep (REMs), rats were recorded for 24h immediately after a single intra-EP administration of N-arachidonoylethanolamine (AEA) or 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-(1-piperidyl)pyrazole-3-carboxamide (AM251; CB1 inverse agonist). Likewise, the effect of these drugs on anxiety and depression was tested by means of the elevated plus maze (EPM) and forced swim test (FST), respectively. Results demonstrate that AEA increases NREMs expression, while AM251 increases W and decreases both NREMs and REMs. In addition, administration of AM251 decreases the time rats spent in the open arms and increases immobility time in the FST. It seems that activation of the CB1R in the EP is important to induce sleep, while its blockade promotes W, as well as anxiety and depression, somewhat resembling insomnia in humans. These results suggest that the EP CB1R is modulating sleep and mood.
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PMID:Entopeduncular nucleus endocannabinoid system modulates sleep-waking cycle and mood in rats. 2358 96