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Addiction Biology Mar 2022In our previous studies, the offspring of morphine-exposed parents (MEO) showed pharmacological tolerance to the morphine's reinforcing effect. According to the role of...
In our previous studies, the offspring of morphine-exposed parents (MEO) showed pharmacological tolerance to the morphine's reinforcing effect. According to the role of exercise in treatment of morphine addiction, the current study was designed to utilize exercise to improve the effect of parental morphine exposure on the morphine's reinforcing effect. Male and female rats received morphine for 10 days and were drug-free for another 10 days. Each morphine-exposed animal was allowed to mate either with a drug-naïve or a morphine-exposed rat. The offspring were divided into two groups: (1) offspring that were subjected to treadmill exercise and (2) offspring that were not subjected to exercise. The reinforcing effect of morphine was evaluated using conditioned place preference (CPP) and two-bottle choice (TBC) tests. Levels of dopamine receptors (D1DR and D2DR), μ-opioid receptor (MOR), and ΔFosB were evaluated in the nucleus accumbens. The MEO obtained lower preference scores in CPP and consumed morphine more than the control group in TBC. After 3 weeks of exercise, the reinforcing effect of morphine in the MEO was similar to the control. D1DR, D2DR, and MOR were increased in MEO compared with the controls before exercise. Levels of D1DR and MOR were decreased after exercise in the MEO; however, D1DR was increased in control. D2DR level did not change after exercise in MEO, but it increased in control group. Moreover, the level of ΔFosB was decreased among MEO while it was increased after exercise. In conclusion, exercise might modulate the reinforcing effect of morphine via alteration in levels of D1DR, MOR, and ΔFosB.
Topics: Animals; Conditioning, Classical; Female; Male; Morphine; Morphine Dependence; Nucleus Accumbens; Rats; Receptors, Dopamine
PubMed: 34931742
DOI: 10.1111/adb.13122 -
British Journal of Clinical Pharmacology May 2016
Topics: Analgesics, Opioid; Dyspnea; Humans; Morphine; Pulmonary Disease, Chronic Obstructive; Surveys and Questionnaires
PubMed: 26632146
DOI: 10.1111/bcp.12856 -
Molecules (Basel, Switzerland) Jun 2023Opioids are considered the most effective analgesics for the treatment of moderate to severe acute and chronic pain. However, the inadequate benefit/risk ratio of... (Review)
Review
Opioids are considered the most effective analgesics for the treatment of moderate to severe acute and chronic pain. However, the inadequate benefit/risk ratio of currently available opioids, together with the current 'opioid crisis', warrant consideration on new opioid analgesic discovery strategies. Targeting peripheral opioid receptors as effective means of treating pain and avoiding the centrally mediated side effects represents a research area of substantial and continuous attention. Among clinically used analgesics, opioids from the class of morphinans (i.e., morphine and structurally related analogues) are of utmost clinical importance as analgesic drugs activating the mu-opioid receptor. In this review, we focus on peripheralization strategies applied to -methylmorphinans to limit their ability to cross the blood-brain barrier, thus minimizing central exposure and the associated undesired side effects. Chemical modifications to the morphinan scaffold to increase hydrophilicity of known and new opioids, and nanocarrier-based approaches to selectively deliver opioids, such as morphine, to the peripheral tissue are discussed. The preclinical and clinical research activities have allowed for the characterization of a variety of compounds that show low central nervous system penetration, and therefore an improved side effect profile, yet maintaining the desired opioid-related antinociceptive activity. Such peripheral opioid analgesics may represent alternatives to presently available drugs for an efficient and safer pain therapy.
Topics: Humans; Analgesics, Opioid; Morphinans; Pain; Analgesics; Morphine; Receptors, Opioid, mu
PubMed: 37375318
DOI: 10.3390/molecules28124761 -
Chemico-biological Interactions Sep 2023Morphine is the most common opioid analgesic administered to treat pain in patients undergoing cancer chemotherapy. This study aimed to evaluate the cytotoxic and...
Morphine is the most common opioid analgesic administered to treat pain in patients undergoing cancer chemotherapy. This study aimed to evaluate the cytotoxic and mutagenic effects of morphine alone and in combination with doxorubicin (Dox), an antineoplastic agent largely used in patients with solid cancers. Cytotoxicity was evaluated in neuroblastoma (SH-SY5Y) and fibroblast (V79) cells using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) colorimetric assay while mutagenicity was assessed using the Salmonella/microsome assay in the absence and in the presence of S9 mix. Morphine showed a cytotoxic effect mainly on SH-SY5Y cells and reduced the cytotoxic effects of Dox when evaluated in a co-treatment procedure. In the Salmonella/microsome assay, it was observed that morphine did not induce mutations and, in fact, decreased the mutagenic effects induced by Dox in TA98 and TA102 strains in the absence of metabolic activation. Furthermore, in the presence of metabolic activation, no induction of mutations was observed with morphine. In conclusion, morphine decreased Dox cytotoxicity in both neuronal and non-neuronal cells and showed antimutagenic effects in the TA102 strain which detects mutagens inducing DNA oxidative damages. However, morphine decreased frameshift mutations induced by Dox in non-cytotoxic concentrations, an effect suggesting interference of Dox intercalation activity that could decrease its chemotherapeutic efficacy. These compelling findings highlight the importance of conducting further studies to explore the potential implications of co-administering morphine and Dox during cancer chemotherapy.
Topics: Humans; Mutagens; Morphine; Mutagenicity Tests; Neuroblastoma; Doxorubicin
PubMed: 37524295
DOI: 10.1016/j.cbi.2023.110652 -
Chemistry (Weinheim An Der Bergstrasse,... Nov 2015In this paper, a new strategy towards the synthesis of codeine and morphine is reported. This new approach features a cascade cyclization to construct the dihydrofuran...
In this paper, a new strategy towards the synthesis of codeine and morphine is reported. This new approach features a cascade cyclization to construct the dihydrofuran ring, and an intramolecular palladium catalyzed C-H olefination of unactivated aliphatic alkene to install the morphinan ring system.
Topics: Alkenes; Catalysis; Codeine; Cyclization; Furans; Hydrogen Bonding; Molecular Structure; Morphine; Palladium
PubMed: 26428413
DOI: 10.1002/chem.201503594 -
Sensors (Basel, Switzerland) Mar 2024Opioid use, particularly morphine, is linked to CNS-related disorders, comorbidities, and premature death. Morphine, a widely abused opioid, poses a significant global...
Opioid use, particularly morphine, is linked to CNS-related disorders, comorbidities, and premature death. Morphine, a widely abused opioid, poses a significant global health threat and serves as a key metabolite in various opioids. Here, we present a turn-off fluorescent sensor capable of detecting morphine with exceptional sensitivity and speed in various samples. The fluorescent sensor was developed through the dimerization process of 7-methoxy-1-tetralone and subsequent demethylation to produce the final product. Despite morphine possessing inherent fluorophoric properties and emitting light in an approximately similar wavelength as the sensor's fluorescent blue light, the introduction of the target molecule (morphine) in the presence of the sensor caused a reduction in the sensor's fluorescence intensity, which is attributable to the formation of the sensor-morphine complex. By utilizing this fluorescence quenching sensor, the chemo-selective detection of morphine becomes highly feasible, encompassing a linear range from 0.008 to 40 ppm with an impressive limit of detection of 8 ppb. Consequently, this molecular probe demonstrates a successful application in determining trace amounts of morphine within urine, yielding satisfactory analytical results. The study also explores the effect of several variables on the sensor's response and optimizes the detection of morphine in urine using a response surface methodology with a central composite design.
Topics: Morphine; Analgesics, Opioid; Fluorescent Dyes; Spectrometry, Fluorescence; Body Fluids
PubMed: 38543983
DOI: 10.3390/s24061722 -
Bioscience Reports Jun 2017The association between the efficacy and safety of dezocine injection and morphine injection for persistence of pain in patients with cancer had yielded controversial... (Comparative Study)
Comparative Study Meta-Analysis Review
The association between the efficacy and safety of dezocine injection and morphine injection for persistence of pain in patients with cancer had yielded controversial results. Therefore, we conduct a meta-analysis of existing observational published studies to assess the relationship between them among Chinese. We conducted a comprehensive research from the databases of PubMed, Web of Science, and Wan Fang Med Online for the related studies up to October 2016. Summary odds ratio (OR) with 95% confidence interval (95% CI) were calculated with the random effects model. Nine published studies comprising 333 dezocine injection patients and 321 morphine injection patients were included in this meta-analysis. Our results suggested that there was no statistical significance between dezocine injection and morphine injection at the case number of effective pain relief (EPR) [OR = 0.97, 95% CI (0.77-1.22), = 0.0, for heterogeneity = 1.000]. However, the rate of adverse drug reaction (ADR) caused by dezocine injection was 56% less than that caused by morphine injection, the difference was statistically significant [OR = 0.44, 95% CI (0.30-0.65), = 0.0, for heterogeneity = 0.980]. No between-study heterogeneity and publication bias were found. In conclusions, this meta-analysis indicates that there is no significant association on the efficacy of persistence of pain in patients with cancer between dezocine injection and morphine injection among Chinese. However, dezocine injection was with less ADR compared with morphine injection.
Topics: Asian People; Bridged Bicyclo Compounds, Heterocyclic; China; Female; Humans; Male; Morphine; Neoplasms; Pain; Tetrahydronaphthalenes
PubMed: 28533424
DOI: 10.1042/BSR20170243 -
Journal of Opioid Management 2020Opioid therapy in pediatrics may be particularly prone to error, yet the incidence of opioid-related medication error and harm has not yet been described in the... (Review)
Review
BACKGROUND
Opioid therapy in pediatrics may be particularly prone to error, yet the incidence of opioid-related medication error and harm has not yet been described in the pediatric inpatient setting.
METHODS
We reviewed a prospectively compiled medication safety database from November 1, 2012 to October 31, 2017. Reports originated from voluntary reporting, hospital code events, naloxone administrations, and reports of unexpected experiences of patient pain. Time, location, error characteristics, drug, route, prescription, error phase, mechanisms, harm, and outcome were collected for all reports. Error and harm were classified by the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) system.
RESULTS
Over 697 opioid medication safety reports were included during the study period. Opioids were administered at a rate of 79.26 administrations per 100 patient bed days, with morphine and hydromorphone administered at 62 versus 15 administrations per 100 bed days, respectively. Overall error rate was 0.94 errors per 10 patient days. Although the absolute rate of error reporting was greater for morphine (0.65 errors reported per 10 opioid administrations) than for hydromorphone, the adjusted incidence of harm was 0.211 per 10 hydromorphone administrations compared to 0.086 per 10 morphine administrations. 47 opioid errors resulted in harm, and administration errors (29) were almost twice as common as prescribing errors (15).
CONCLUSIONS
We report and aim to establish a comparative reference point for incidence of opioid-related error and harm adjusted for both hospital bed days and total opioid administrations within the pediatric hospital inpatient setting based on the above findings.
Topics: Analgesics, Opioid; Child; Hospitals, Pediatric; Humans; Medication Errors; Morphine; Time
PubMed: 33226094
DOI: 10.5055/jom.2020.0592 -
Pediatric Annals Nov 2015Neonatal pain management has evolved dramatically in the past few decades. Evidence is clear that neonates experience pain. Furthermore, we are increasingly aware of the... (Review)
Review
Neonatal pain management has evolved dramatically in the past few decades. Evidence is clear that neonates experience pain. Furthermore, we are increasingly aware of the detrimental effects of untreated neonatal pain during a critical period of neuronal maturation. Providing safe and effective pain relief is a primary goal of neonatal critical care specialists to ensure good outcomes. However, there are lingering concerns regarding the harmful effects of sedative-analgesics on the developing brain. Thus, striking a fine balance between effective analgesia and avoiding serious short- and long-term adverse effects from pain medications remains a major challenge for caregivers.
Topics: Child Development; Humans; Infant, Newborn; Infant, Premature; Morphine; Pain
PubMed: 26587818
DOI: 10.3928/00904481-20151112-08 -
Addiction Biology Feb 2024Humans demonstrate significant behavioural advantages with particular perceptual dimensions (such as colour or shape) and when the relevant dimension is repeated in...
Humans demonstrate significant behavioural advantages with particular perceptual dimensions (such as colour or shape) and when the relevant dimension is repeated in consecutive trials. These dimension-related behavioural modulations are significantly altered in neuropsychological and addiction disorders; however, their underlying mechanisms remain unclear. Here, we studied whether these behavioural modulations exist in other trichromatic primate species and whether repeated exposure to opioids influences them. In a target detection task where the target-defining dimension (colour or shape) changed trial by trial, humans exhibited shorter response time (RT) and smaller event-related electrodermal activity with colour dimension; however, macaque monkeys had shorter RT with shape dimension. Although the dimensional biases were in the opposite directions, both species were faster when the relevant dimension was repeated, compared with conditions when it changed, across consecutive trials. These indicate that both species formed dimensional sets and that resulted in a significant 'switch cost'. Scheduled and repeated exposures to morphine, which is analogous to its clinical and recreational use, significantly augmented the dimensional bias in monkeys and also changed the switch cost depending on the relevant dimension. These cognitive effects occurred when monkeys were in abstinence periods (not under acute morphine effects) but expressing significant morphine-induced conditioned place preference. These findings indicate that significant dimensional biases and set formation are evolutionarily preserved in humans' and monkeys' cognition and that repeated exposure to morphine interacts with their manifestation. Shared neural mechanisms might be involved in the long-lasting effects of morphine and expression of dimensional biases and set formation in anthropoids.
Topics: Humans; Animals; Morphine; Haplorhini; Analgesics, Opioid; Conditioning, Classical; Cognition
PubMed: 38333998
DOI: 10.1111/adb.13380