Mechanisms of Morphine Enhancement of Spontaneous Seizure Activity

Saboory, Ehsan; Derchansky, M.; Ismaili, Mohammed; Jahromi, S. S.; Brull, Richard; Carlen, Peter L.; Beheiry, Hossam El

doi:10.1213/01.ane.0000287675.15225.0b

Cited by 68 publications

(38 citation statements)

References 26 publications

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“…Enkephalin inhibited GABA release from inhibitory interneurons, resulting in increased excitability of hippocampal pyramidal cells and dentate gyrus granule cells. The role of enkephalins as pro-convulsive agents is also consistent with the seizureinducing side-effect of high concentration morphine treatment [134,135]. Prodynorphin-derived peptides primarily acted at presynaptic kappa opioid receptors to inhibit excitatory amino acid release from perforant path and mossy fiber terminals [108,136].…”

Section: Dynorphin and Enkephalinmentioning

confidence: 71%

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

Dobolyi¹,

Kékesi²,

Juhász³

et al. 2014

CMC

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Neuropeptides are signaling molecules participating in the modulation of synaptic transmission. Neuropeptides are stored in dense core synaptic vesicles, the release of which requires profound excitation. Only in the extracellular space, neuropeptides act on G-protein coupled receptors to exert a relatively slow action both pre-and postsynaptically. Consequently, neuropeptide modulators are ideal candidates to influence epileptic tissue overexcited during seizures. Indeed, a number of neuropeptides have been implicated in epilepsy and many of them are considered to have endogenous neuroprotective actions. Neuropeptides, present in the hippocampus, the most frequent focus of seizures in temporal lobe epilepsy, received the largest attention as potential anti-epileptic substances. Hippocampal neuropeptides, somatostatin, neuropeptide Y, galanin, dynorphin, enkephalin, substance P, cholecystokinin, vasoactive intestinal polypeptide, and some neuropeptides, which are also hormones such as ghrelin, angiotensins, corticotropin-releasing hormone, adrenocorticotropin, thyrotropin-releasing hormone, oxytocin and vasopressin involved in epilepsy are discussed in the review article. Oral application of neuropeptides as drugs is typically not efficient because of low bioavailability: rapid degradation and insufficient penetration through the blood-brain barrier. Recent progress in the development of non-peptide agonists and antagonists of neuropeptide receptors as well as gene therapeutic approaches leading to the local production of neuropeptides within the central nervous system will also be discussed.

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Section: Dynorphin and Enkephalinmentioning

confidence: 71%

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

Dobolyi¹,

Kékesi²,

Juhász³

et al. 2014

CMC

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“…It is not clear if this represents a compensatory mechanism against epilepsy because multiple factors determine the anticonvulsant or proconvulsant role of opioids in the brain. For example, morphine depresses electrographic seizure activity under a low concentration, while enhances seizure activity under high concentrations with an apparent dose-dependent manner [217, 223]. SCN80, a non-peptide DOR agonist, both in low or high dose, produced convulsions in the rat, but had little effects in rhesus monkeys [215, 224, 225].…”

Section: Advances In Research On Opioid Receptor Functionsmentioning

confidence: 99%

Current Research on Opioid Receptor Function

Feng

He²,

Yang³

et al. 2012

CDT

284

186

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The use of opioid analgesics has a long history in clinical settings, although the comprehensive action of opioid receptors is still less understood. Nonetheless, recent studies have generated fresh insights into opioid receptor-mediated functions and their underlying mechanisms. Three major opioid receptors (μ-opioid receptor, MOR; δ-opioid receptor, DOR; and κ-opioid receptor, KOR) have been cloned in many species. Each opioid receptor is functionally sub-classified into several pharmacological subtypes, although, specific gene corresponding each of these receptor subtypes is still unidentified as only a single gene has been isolated for each opioid receptor. In addition to pain modulation and addiction, opioid receptors are widely involved in various physiological and pathophysiological activities, including the regulation of membrane ionic homeostasis, cell proliferation, emotional response, epileptic seizures, immune function, feeding, obesity, respiratory and cardiovascular control as well as some neurodegenerative disorders. In some species, they play an essential role in hibernation. One of the most exciting findings of the past decade is the opioid-receptor, especially DOR, mediated neuroprotection and cardioprotection. The up-regulation of DOR expression and DOR activation increase the neuronal tolerance to hypoxic/ischemic stress. The DOR signal triggers (depending on stress duration and severity) different mechanisms at multiple levels to preserve neuronal survival, including the stabilization of homeostasis and increased pro-survival signaling (e.g., PKC-ERK-Bcl 2) and anti-oxidative capacity. In the heart, PKC and KATP channels are involved in the opioid receptor-mediated cardioprotection. The DOR-mediated neuroprotection and cardioprotection have the potential to significantly alter the clinical pharmacology in terms of prevention and treatment of life-threatening conditions like stroke and myocardial infarction. The main purpose of this article is to review the recent work done on opioids and their receptor functions. It shall provide an informative reference for better understanding the opioid system and further elucidation of the opioid receptor function from a physiological and pharmacological point of view.

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“…Pfeiffer et al showed that endogenous opioids including β-endorphin, enkephalins and dynorphins and also opiate receptors have an important role in regulation of several neuroendocrine functions [13]. It has been shown that opioids inhibit luteinizing hormone (LH) and thyrotropin secretion in rats [14]. Opioids control neuroendocrine processes in hypothalamic level through releasing hypothalamic releasing or inhibiting factors [15].…”

Section: Introductionmentioning

confidence: 99%

The effect of opium addiction on thyroid function tests

Gozashti

Mohammadzadeh

Divsalar

et al. 2014

J Diabetes Metab Disord

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BackgroundA number of abnormalities has been identified among drug addicted users especially heroin addicts. However, there are a few studies to assess the opium effects on thyroid hormones. the aim of the present study is to investigate the effect of opium on the thyroid function tests.MethodIn this case–control, 50 male addicts, aged 20–50 years, with history of addiction to opium lasting more than two years, and 50 male non-addicts as control group were randomly selected. 10 cc blood sample was taken for measurements of TSH, total T4 and T3, free T4 and T3, and T3 resin uptake (T3RU) and 50 cc urine sample for opium testing.ResultsThe univariate analysis revealed that there was not a significant association between opium and serum levels of T4 and TSH, but compared with control group, a slight increase in total T3 and a decrease in T3RU were observed among addicts (P < 0.05). In multivariate analysis, opium was also found to exert a lowering effect on serum free T4 level after adjusting of age and cigarette smoking (P < 0.05).ConclusionThe findings of the present study demonstrated that opium can influence on thyroid function by increasing total T3 and decreasing T3RU and free T4 levels.

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Mechanisms of Morphine Enhancement of Spontaneous Seizure Activity

Cited by 68 publications

References 26 publications

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

Current Research on Opioid Receptor Function

The effect of opium addiction on thyroid function tests

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