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Neurobiology of opioid addictionRudén, Ludvig January 2018 (has links)
Since the use of opioids started to emerge for analgesic reasons in the 19th century with the synthetization of morphine, opioids have been studied rigorously to better understand its effects on the brain. This thesis shows that both the analgesic effects and the reinforcing effects of opioids are mediated by the same receptor, the mu opioid receptor (MOR). MOR activity has been correlated to both primary and secondary reinforcers and should be considered to cause positive reinforcement together with increases in dopamine transmission for all drugs of abuse, and not only in relation to opioids. Opioid tolerance, dependence and even addiction are to some extent thought to relate to opioids’ acute effect of cyclic adenosine monophosphate (cAMP) superactivation. Based upon these findings, the allostasis theory of addiction is considered to be the most suitable in defining opioid addiction. The theory claims that the mesolimbic dopamine system becomes sensitized, increasing the attractiveness of opioids. This while counteradaptation increases the pleasurable tolerance of opioids, encouraging the user to increase its intake for the same initial reward. Furthermore the theory claims that cAMP superactivation is causing an unfolding effect of neurobiological and neurochemical expressions which leads to the disorder of addiction. cAMP superactivation is mediating the negatively reinforcing aspects of opioid addiction together with changes to corticotropin-releasing factor (CRF) in the brain stress system, such as the hypothalamic-pituitary-adrenal (HPA) axis and the extended amygdala.
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EVALUATION OF NATURALLY OCCURRING OPIOIDS AND SYNTHETIC DERIVATIVES FOR THERAPEUTIC APPLICATION IN ALCOHOL ABUSE AND PAINAnna M Gutridge (11819636) 19 December 2021 (has links)
<div>
<p>Historically, natural products
from plants, fungi, bacteria and animals have played an important role in the
discovery of new drugs. In fact, it has been found that 34% of new FDA-approved
drugs over the last 30 years were derived from natural products or their
derivatives. Because of the chemical and structural diversity of natural
products, they continue to be one of the best options for discovering novel
compounds and scaffolds; this is especially true for compounds targeting the
µ-, δ-, and κ- opioid receptors. However, traditional opioids such as morphine cause
many therapeutically limiting side effects. Therefore, there have been immense
efforts to develop opioids that avoid these side effects, with “signal-biased”
compounds being an intense area of interest. The research presented here investigates
of the biased mechanisms of compounds found in and derived from <i>Mitragyna
speciosa</i>, also known as kratom, and <i>Picralima nitida</i>, also known as
akuamma. Kratom and akuamma compounds are examined for their therapeutic
potential in treating alcohol abuse and pain, respectively, two prevalent
conditions with extreme societal and economic costs.</p>
</div>
<br>
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Uncovering the Functional Implications of Mu- and Delta-opioid Receptor Heteromerization in the BrainKabli, Noufissa 20 June 2014 (has links)
Opioid Receptors (ORs) are involved in the pathophysiology of several neuropsychiatric conditions yet remain an untapped therapeutic resource. Although only mu-, delta-, and kappa-OR types have been cloned, additional subtypes result from complexes generated by direct receptor-receptor interactions. Mu- and delta-ORs form a heteromeric receptor complex with unique pharmacological and signalling properties distinct from those of mu- and delta-OR homomers. In these studies, we sought to characterize the ligand binding pocket and agonist-induced internalization profile of the mu-delta heteromer, to investigate mu-delta heteromer-specific signalling in brain, and to interrogate the contribution of this receptor complex to opioid-mediated behavioural effects.
In competition radioligand binding studies, delta-agonists displaced high affinity mu-agonist binding from the mu-delta heteromer but not the muOR homomer, suggestive of delta-agonists occupying or allosterically modulating the muOR ligand binding pocket within the heteromer. Delta-agonists induced internalization of the mu-delta heteromer in a dose-dependent, pertussis toxin resistant, and muOR- and deltaOR-dependent manner from the cell surface via the clathrin and dynamin endocytic machinery. Agonist-induced internalization of the mu-delta heteromer persisted following chronic morphine treatment conditions which desensitized the muOR homomer.
Using Galpha-specific GTPgammaS binding assays, we demonstrated that mu-delta heteromer signalling previously characterized in cell lines was present in the striatum and hippocampus, and did not desensitize following prolonged morphine treatment conditions which desensitized muOR homomer-mediated signalling.
Since delta-agonists which also target the mu-delta heteromer possess antidepressant-like and anxiolytic-like properties, we investigated the role of this receptor complex in mood regulation. We devised a strategy to selectively analyze the effects of the mu-delta heteromer by dissociating it using a specific interfering peptide aimed at a sequence implicated in mu-delta heteromerization. The interfering peptide abolished the unique pharmacological and trafficking properties of delta-agonists at the mu-delta heteromer and dissociated this receptor complex in vitro. Intra-accumbens administration of the interfering peptide disrupted the mu-delta interaction in vivo and allowed for isolation of the mu-delta heteromer contribution to the mood-regulatory effects of a delta-agonist with activity at the heteromer. Activation of the mu-delta heteromer in the nucleus accumbens produced antidepressant-like and anxiolytic-like actions in animal models of depression and anxiety.
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Uncovering the Functional Implications of Mu- and Delta-opioid Receptor Heteromerization in the BrainKabli, Noufissa 20 June 2014 (has links)
Opioid Receptors (ORs) are involved in the pathophysiology of several neuropsychiatric conditions yet remain an untapped therapeutic resource. Although only mu-, delta-, and kappa-OR types have been cloned, additional subtypes result from complexes generated by direct receptor-receptor interactions. Mu- and delta-ORs form a heteromeric receptor complex with unique pharmacological and signalling properties distinct from those of mu- and delta-OR homomers. In these studies, we sought to characterize the ligand binding pocket and agonist-induced internalization profile of the mu-delta heteromer, to investigate mu-delta heteromer-specific signalling in brain, and to interrogate the contribution of this receptor complex to opioid-mediated behavioural effects.
In competition radioligand binding studies, delta-agonists displaced high affinity mu-agonist binding from the mu-delta heteromer but not the muOR homomer, suggestive of delta-agonists occupying or allosterically modulating the muOR ligand binding pocket within the heteromer. Delta-agonists induced internalization of the mu-delta heteromer in a dose-dependent, pertussis toxin resistant, and muOR- and deltaOR-dependent manner from the cell surface via the clathrin and dynamin endocytic machinery. Agonist-induced internalization of the mu-delta heteromer persisted following chronic morphine treatment conditions which desensitized the muOR homomer.
Using Galpha-specific GTPgammaS binding assays, we demonstrated that mu-delta heteromer signalling previously characterized in cell lines was present in the striatum and hippocampus, and did not desensitize following prolonged morphine treatment conditions which desensitized muOR homomer-mediated signalling.
Since delta-agonists which also target the mu-delta heteromer possess antidepressant-like and anxiolytic-like properties, we investigated the role of this receptor complex in mood regulation. We devised a strategy to selectively analyze the effects of the mu-delta heteromer by dissociating it using a specific interfering peptide aimed at a sequence implicated in mu-delta heteromerization. The interfering peptide abolished the unique pharmacological and trafficking properties of delta-agonists at the mu-delta heteromer and dissociated this receptor complex in vitro. Intra-accumbens administration of the interfering peptide disrupted the mu-delta interaction in vivo and allowed for isolation of the mu-delta heteromer contribution to the mood-regulatory effects of a delta-agonist with activity at the heteromer. Activation of the mu-delta heteromer in the nucleus accumbens produced antidepressant-like and anxiolytic-like actions in animal models of depression and anxiety.
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Participação dos receptores delta e kappa -opioides centrais no controle do apetite por sódio em ratos estimulados a ingerir solução salina hipertônicaNascimento, Ana Isabel Reis January 2015 (has links)
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Previous issue date: 2015 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Alguns estudos sugerem que as vias opioidérgicas centrais parecem desempenhar um papel
regulatório no controle da ingestão de água e sal em mamíferos. As ações dos opioides centrais
sobre a regulação do controle hidroeletrolítico são mediadas por vários dos subtipos de
receptores opioides. O papel dos receptores delta e kappa-opioides centrais neste processo não
está adequadamente elucidado sendo necessário mais estudos que o esclareçam. Objetivo: Este
estudo investigou o envolvimento dos receptores delta e kappa-opioides centrais no apetite por
sódio em ratos depletados deste íon e em rato ativados centralmente com angiotensina. Material
e Métodos: Foram utilizados ratos Wistar (270 ± 20 g), submetidos à cirurgia estereotáxica para
implante de cânula guia no ventrículo lateral esquerdo (VL), no órgão subfornical (OSF), no
núcleo preóptico mediano (MnPO) e no núcleo basolateral da amígdala (BLA). No protocolo de
depleção de sódio os animais foram submetidos à injeção subcutânea de furosemida combinada
com dieta hipossódica quatro dias após a cirurgia. Neste modelo de estudo os animais
receberam injeção intracerebroventricular (i.c.v.) do antagonista delta-opioide naltrindole no
quinto dia pós-cirúrgico, nas doses de 5, 10 e 20 nmol/2 μL e do antagonista kappa-opioide,
norbinaltorfimina, injetado no OSF, MnPO e BLA, nas doses de 0,5, 1,0 e 2,0 nmol/0,2 μL.. O
agonista específico para os receptores delta-opioides, deltorfina II (2,5, 5,0, 10 e 20 nmol/2 μL),
foi injetado i.c.v. em animais depletados de sódio pré-tratados com naltrindole na dose de 20
nmol/2 μL e em animais repletos de sódio na dose de 20 nmol/2 μL. O agonista kappa-opioide,
ICI199,441 (2,0 nmol/0,2 μL) foi injetado no OSF, MnPO e BLA em animais depletados de sódio
pré-tratados com norbinaltorfimina 2,0 nmol/0,2 μL e em animais repletos de sódio na dose de
2,0 nmol/0,2 μL. Bebedouros de água destilada (H2Od) e de salina foram introduzidos nas
caixas15 minutos após a injeção central e tiveram seus volumes monitorados nos tempos 5, 10,
15, 30, 45, 60, 90 e 120 minutos, após a colocação dos bebedouros. No protocolo de ativação
angiotensinérgica central, quarto dia após a cirurgia os animais sofreram administração i.c.v. de
naltrindole (5, 10 e 20 nmol/2 μL) 15 minutos antes de receberem injeções de angiotensina II na
dose de 10 ng/2 μL. Os bebedouros de H2Od e de solução salina foram introduzidos nas caixas
logo após a segunda injeção e tiveram seus volumes monitorados nos tempos 5, 10, 15, 30, 45,
60, 90 e 120 minutos, após a colocação dos bebedouros. Para verificar a especificidade de ação
dos antagonistas opioides os animais foram submetidos aos testes de sobremesa, campo aberto e
medida da pressão arterial. A análise estatística utilizada foi ANOVA modelo misto para
medidas repetidas seguida do pós-teste de Bonferroni para múltiplas comparações dos volumes
ingeridos e teste “t” de Student não pareado para análise dos testes de comportamento, através
do programa GraphPad Prism 6.0. Resultados: Os grupos de ratos que receberam injeções i.c.v.
de naltrindole após depleção de sódio e ativação angiotensinérgica central, apresentaram
redução estatisticamente significante na ingestão de salina quando comparados ao grupo de
animais controles. Os ratos que receberam injeção de norbinaltorfimina no OSF, MnPO e BLA
após depleção de sódio apresentaram redução estatisticamente significante na ingestão de salina
quando comparados ao grupo de animais controles. A estimulação dos receptores delta-opioides
em animais repletos de sódio aumentou a ingestão de salina hipertônica. Conclusões: Os dados
presentes sugerem que os receptores delta-opioides centrais e os receptores kappa-opioides
localizados no OSF, MnPO e BLA parecem desempenhar papel fundamental na expressão do
comportamento de aquisição de sal em ratos que sofreram depleção de sódio e ativação central
do apetite por sódio induzido pela via angiotensinérgica. / Central opioid pathways seem to have an important role on the control of water and salt
intake in mammals, and brain opioid peptides may influence hydroelectrolyte balance
through a myriad of actions mediated by distinct opioid receptors. The specific role of
central delta and kappa-opioid receptors (DOR and KOR) in this process is far from
being fully understood. In the present work, we investigated the role of those receptors
in the control of water and salt intake, in sodium-depleted rats and rats with activation
central angiotensinergic. Method: Wistar male rats (250 ± 20 g) were used in the
experiment after stereotaxic cannulation of the VL left, SFO, MnPO and BLA. To study
the effect of the blockade of central DOR and KOR on water and salt intake in rats were
sodium depleted by the concomitant use of s.c. injections of furosemide and were kept in
hypossodic diet, five days after surgery. In the sixth day, they received i.c.v. injections
of a selective delta-opioid receptor antagonist (naltrindole) at the doses of 5, 10 and 20
nmol/2 μL and injections in the SFO, MnPO and BLA of a selective kappa-opioid
receptor antagonist (norbinaltorphimine) at the doses of 0.5, 1.0 and 2.0 nmol/0.2 μL.
The specific agonist for delta-opioid receptor deltorphin II (2.5, 5.0, 10 and 20 nmol / 2 !L)
was injected i.c.v. in animals depleted pretreated with sodium naltrindole at the dose 20 nmol
/2 !L . The kappa-opioid agonist, ICI199,441 (2 nmol /0.2 !L) was injected into the SFO,
MnPO and BLA in animals depleted pretreated with sodium norbinaltorphimine 2.0 nmol /
0.2 !L. Bottles containing water or hypertonic saline solution were introduced into the cages
15 min after the central administration. To study the effect of the blockade of central DOR
and KOR on water and salt intake in animals after central angiotensinergic stimulation,
the animals received intracerebroventricular injections of naltrindole at the doses of 5,
10 and 20 nmol/2 μL 30 min before receiving central injections of angiotensin II at the dose
of 10 ng/2 μL. In this case, bottles containing water or hypertonic saline solution were
introduced into the cages immediately after the central administration of angiotensin II.
Water and salt intake were recorded for the next 2 hours after the introduction of the bottles
into the cages. To verify the specificity of action of opioid antagonists animals were submitted
to the dessert test, open field and measurement of blood pressure. Data were analyzed by
Two-Way ANOVA mixed model followed by Bonferroni as post-hoc test. Results: The
groups of rats that received i.c.v. injections naltrindole after sodium depletion and central
angiotensinergic activation, showed a statistically significant reduction in salt intake when
compared to control animals group. Rats receiving norbialtorphimine injection in the SFO,
MnPO and BLA after sodium depletion showed a statistically significant reduction in salt
intake when compared to control animals group. The stimulation of delta-opioid receptors in
animals full of sodium increased intake of hypertonic saline. Conclusions: The present data
suggest that the delta-opioid receptors central, and the kappa-opioid receptors located in the
SFO, MnPO and BLA appear to play a key role in the expression of the salt acquisition
behavior in rats with sodium appetite.
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Regulation of the endogenous opioid system by acute nicotine and nicotine withdrawalMcCarthy, Michael J. 27 April 2004 (has links)
No description available.
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Design, Synthesis, and Biological Screening of Selective Mu Opioid Receptor Ligands as Potential Treatments for Opioid AddictionObeng, Samuel 01 January 2017 (has links)
Today, more Americans die each year because of drug overdoses than are killed in motor vehicle accidents. In fact, in 2015, more than 33,000 individuals died due to an overdose of heroin or prescription opioids. Sadly, 40-60 % of patients on current opioid addiction treatment medications relapse. Studies have shown that the addiction/abuse liability of opioids are abolished in mu opioid receptor (MOR) knock-out mice; this indicates that the addiction and abuse liability of opioids are mainly mediated through MOR. Utilizing the “message-address concept”, the our laboratory reported a novel non-peptide, reversible MOR selective ligand 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α (isoquinoline-3-carboxamido)morphinan (NAQ). Molecular modeling and mutagenesis studies revealed that the selectivity of NAQ for MOR is because of the π-π stacking of the isoquinoline ring of NAQ with W318.
Therefore, other heterocyclic ring systems were explored to obtain a diverse library of compounds with similar or different molecular interactions and pharmacologic characteristics as NAQ. The newly designed compounds were indole analogs of 6α/β-naltrexamine. The compounds were synthesized and the affinity and selectivity for MOR determined using the radioligand binding assay while the functional activity at MOR was determined using the [35S]GTPγS binding assay. The indole analog of 6α-naltrexamine substituted at position 7 (compound 6) was found to be very potent and had the lowest efficacy in the [35S]GTPγS functional assay while the indole analog of 6β-naltrexamine substituted at position 2 (compound 10) was identified as a MOR agonist and had the greatest efficacy. In vivo studies were conducted using the warm-water immersion assay to find whether the synthesized compounds had antinociceptive effects and/or blocked the antinociceptive effects of morphine. Not surprisingly, compound 10 was identified as an opioid agonist while compound 6 almost completely blocked morphine’s antinociceptive effects. The opioid antagonist effect of compound 6 was found to be dose dependent with an AD50 of 2.39 mg/kg (0.46-12.47). An opioid withdrawal assay was conducted on compound 6 using morphine-pelleted mice. Compound 6 produced significantly less withdrawal symptoms at 50 mg/kg than naltrexone at 1 mg/kg. Therefore, compound 6 has the potential to be used in opioid addiction and withdrawal treatment.
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Design, Synthesis, and Biological Evaluation of Novel Peptide Ligands as Kappa Opioid Receptor AntagonistsRamos-Colon, Cyf Nadine, Ramos-Colon, Cyf Nadine January 2016 (has links)
Millions of people in the US currently suffer from chronic pain but available therapeutics do not provide effective chronic pain treatment. Opiate therapy is still the gold standard for chronic pain management with detrimental side effects, such as tolerance, addiction, constipation, and respiratory depression that limit their therapeutic potential. Opiates exert their positive and negative effects by activating the μ opioid receptor (MOR). Conversely, the κ opioid receptor (KOR) has been shown to modulate the tolerance and addiction produced by MOR agonists and is also involved in mood modulation (anxiety and depression). Therefore, blocking KOR activation results in positive effects against opiate side effects and stress-related depression. Dynorphin A (Dyn A) is the endogenous opioid peptide for the KOR. Structure-activity relationship (SAR) studies were carried out to develop a KOR selective antagonist based on the Dyn A structure. A minimum Dyn A pharmacophore with improved stability, no cell toxicity, and antagonist activity was discovered. Peptidomimetic enkephalin analogues previously developed in our group as MOR and δ opioid receptor (DOR) agonists have shown multifunctional activity, with MOR/DOR agonist and KOR antagonist activities. To our knowledge, this finding is first of its class for the opioid receptors. Novel design and synthesis of KOR selective ligands based on our multifunctional enkephalin analogues was done. Successful peptide synthesis resulted in analogues with high stability in rat plasma and no cell toxicity.
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Multiple Cell Signaling Pathways Modulate the Cocaine-Induced Increase in Mu Opioid Receptor Protein Expression in PC12 CellsSoftah, Abrar 27 May 2013 (has links)
Cocaine is interrelated with the opioid system on many levels, especially via the mu opioid receptor (MOR). Also, cocaine has been involved in modulating nitric oxide (NO) actions within the cell. The effect of cocaine was first assessed on the MOR, and then on transcription by the use of 1 µg/ mL actinomycin D inhibitor. Several signaling pathways that cocaine may exert its action in modulating the MOR up-regulation in protein expression were also explored. Two dosage regimens were used in cocaine treatment, single continuous treatment (SCT), and repeated intermittent treatment (RIT). Different pathway inhibitors were used on PC12 cells, as follows: the PLC-PKC inhibitors 5 µM U-73122 and 10 µM BIS-1 used to investigate the involvement of the PKC signaling pathways in MOR expression levels, the evaluation of MAPK pathway by the use of 50 µM U0126 inhibitor, and the 10 µM LY94002 inhibitor was used to investigate the PI3K/Akt pathway. Moreover, the effect of NO on these signaling pathways was investigated by the use of 20 mM nonselective L-NAME inhibitor and qualitatively by DAF-2 florescence. Western blot analysis indicated that cocaine up-regulated MOR protein expression. Also, RIT cocaine treatment increased MOR protein levels via transcription. All three signaling pathways, MAPK, Akt and PKC modulated cocaine-induced increase of MOR following SCT cocaine treatment (post-transcriptional). Both MAPK and Akt have been found to modulate the cocaine-induced transcription of MOR via the two dosage regimens of cocaine, SCT and RIT. Also, inhibition of both PLC and PKC did not prevent cocaine-induced increase in MOR transcription, according to RIT of cocaine.
Furthermore, Akt and PKC appeared to modulate cocaine-induced NO production while MAPK did not. NO seemed to be involved with the PKC and Akt pathways in up-regulating MOR in RIT of cocaine directly by the Akt pathway, and indirectly by the PKC pathway. On the other hand, NO and MAPK modulated the MOR up-regulation expression simultaneously, but in an individual/parallel manner. Furthermore, signaling pathway activation levels were tested using L-NAME which concluded that NO modulated cocaine-induced increase in total Akt protein levels, but did not appear to have an effect on phosphorylated MAPK activation levels. In conclusion, different treatment regimens of cocaine activate different pathways; SCT of cocaine activated all three signaling pathways, however, RIT of cocaine activated only the MAPK and Akt pathways. / Saudi Bureau in Canada
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The influence of opioids on gastric function : experimental and clinical studiesWalldén, Jakob January 2008 (has links)
Efter operation och anestesi får patienter ofta en negativ påverkan på magsäck och tarmar. Illamående och kräkningar är ett stort problem och många har svårt att komma igång med intag av föda och normal tarmfunktion då magsäcken och tarmarna ”står stilla”. Flera faktorer bidrar- bl.a. smärtan, det kirurgiska traumat och de läkemedel vi ger i samband med anestesin. Av de senare är opioider, d.v.s morfin och morfinliknande läkemedel, starkt bidragande. I detta avhandlings- arbete har opioiders effekter på magsäckens motilitet studerats. Med ett absorptionstest (paracetamolmetoden) studerades hos frivilliga hur opioiden remifentanil påverkar magsäckstömning och om kroppspositionen har betydelse för tömningshastigheten ut i tarmen. Remifentanil fördröjde magsäcks-tömningen och under pågående opioid behandling hade kroppspositionen ingen större betydelse, vilket det däremot hade under kontrollförsöken. Med samma metod jämförde vi hos patienter två anestesimetoder och studerade magsäcks-tömning direkt efter en operation. Ingen skillnad kunde påvisas mellan en opioidbaserad och en opioidfri anestesi, men inom respektive grupp var det en stor variation i magsäckstömning mellan individerna. Med en barostat studerades tonus i övre delen av magsäcken. Hos hälften av de frivilliga orsakade remifentanil en ökning av tonus och hos den andra hälften en minskning av tonus. Vidare undersöktes hos en grupp patienter opioiden fentanyls påverkan på den elektriska aktiviteten i magsäcken. Med en elekroga-strograf (EGG) registrerades de långsamma elektriska vågor som koordinerar muskelrörelserna i magsäcken. Hos hälften av de undersökta påverkades aktiviteten av fentanyl med en sänkt vågfrekvens eller upphörande av vågor, medan aktiviteten var opåverkad hos den övriga hälften. För att finna en förklaring till variationen gjordes genetiska analyser av genen för opioidreceptorn hos de undersökta i barostat och EGG studierna. Variationer i genomet, s.k. polymorfism, var inte associerad till utfallen i studierna. Studierna har visat på att opioider har en uttalad effekt på magsäckens motilitet och att den varierar kraftigt mellan individer. Polymorfism i genen för opioid- receptorn förklarade inte skillnaden mellan individer. Direkt efter operation bidrar sannolikt andra faktorer än anestesimetod till det variabla utfallet i magsäckstömning. / After anesthesia and/or surgical procedures, gastrointestinal motility is commonly impaired. The causes are multifactorial, with surgical trauma, pain and perioperative drugs playing a major role. This thesis explores opioid effects on gastric motility in healthy volunteers and patients undergoing surgery. Gastric emptying was studied by an absorption test (paracetamol method), and in healthy volunteers a remifentanil infusion delayed gastric emptying. Body position altered emptying during the control situations, but not during the remifentanil infusion. Further, two anesthetic methods were compared and no differences were found in immediate postoperative gastric emptying between a remifentanil/propofol based intravenous anesthesia and an opioid free inhalational anesthesia, although the interindividual variability was high. Proximal gastric tone was studied using a gastric barostat. An infusion of remifentanil caused two patterns of reaction regarding gastric tone, with half of the subjects increasing and half decreasing in gastric tone. Gastric myoelectrical activity was evaluated with electrogastrography (EGG), and a bolus dose of fentanyl caused a decrease in frequency of the gastric slow waves or disrupted this activity. However, the activity was unaffected in half of the investigated subjects. Analysis of polymorphisms (A118G and G691C) in the µ-opioid receptor gene was performed to find an explanation for the great interindividual variations seen in the barostat and EGG studies, but no association could be found. These studies have shown that opioids have pronounced effects on gastric motility with variable individual responses that are difficult to predict. Polymorphisms in the µ-opioid receptor gene could not explain the variations. Postoperatively, other factors might contribute more than opioids to the impairment in gastric motility. / ISSN 1652-4063
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