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Bioorganic & Medicinal Chemistry Dec 2010A series of benzyl esters of meperidine and normeperidine were synthesized and evaluated for binding affinity at serotonin, dopamine and norepinephrine transporters. The...
A series of benzyl esters of meperidine and normeperidine were synthesized and evaluated for binding affinity at serotonin, dopamine and norepinephrine transporters. The 4-methoxybenzyl ester 8b and 4-nitrobenzyl ester 8c in the meperidine series and 4-methoxybenzyl ester 14a in the normeperidine series exhibited low nanomolar binding affinities at the SERT (K(i) values <2nM) and high SERT selectivity (DAT/SERT >1500 and NET/SERT >1500).
Topics: Esters; Ligands; Meperidine; Serotonin Plasma Membrane Transport Proteins; Selective Serotonin Reuptake Inhibitors; Structure-Activity Relationship
PubMed: 20980153
DOI: 10.1016/j.bmc.2010.09.060 -
Bioscience Reports Feb 2019Meperidine used to control shivering during perioperative period has associated side effects. The present study compared the safety of selective α2-adrenoreceptor... (Randomized Controlled Trial)
Randomized Controlled Trial
Meperidine used to control shivering during perioperative period has associated side effects. The present study compared the safety of selective α2-adrenoreceptor agonist dexmedetomidine and meperidine for anti-shivering in primiparas after caesarean delivery under combined spinal-epidural anesthesia (CSEA). 100 primiparas scheduled for caesarean delivery were randomly allocated to dexmedetomidine group (Group D, =50) and meperidine positive control group (Group M, =50). Primiparas experienced shivering that continued to cord clamping were treated with dexmedetomidine (0.5 μg/kg) or meperidine (0.5 mg/kg) after cord clamping. The primary outcome measures were incidence of nausea, vomiting, and respiratory depression. Secondary outcome measures were shivering score, vital signs including blood pressure, heart rate and O saturation, tympanic temperature, and sedation score. Dexmedetomidine provided similar anti-shivering effects as meperidine in patients after caesarean delivery under CSEA, evidenced as all shivering primiparas responded to either dexmedetomidine or meperidine treatment within 15 min. However, incidence of nausea and vomiting were significantly lower after dexmedetomidine treatment, accompanied with more stable blood pressure. Dexmedetomidine also provided well regulation of tympanic temperature and good sedation. Selective α-adrenoreceptor agonist dexmedetomidine has a better safety profile compared with meperidine for anti-shivering in primiparas undergoing caesarean delivery. Dexmedetomidine could be a better choice for anti-shivering in patients requiring caesarean section. The mechanism of anti-shivering for dexmedetomidine may relate to well regulation of temperature and good sedation.
Topics: Administration, Intravenous; Adrenergic alpha-2 Receptor Agonists; Adult; Anesthesia, Epidural; Anesthesia, Spinal; Body Temperature Regulation; Cesarean Section; Dexmedetomidine; Double-Blind Method; Female; Humans; Meperidine; Postoperative Care; Pregnancy; Shivering; Treatment Outcome
PubMed: 30643009
DOI: 10.1042/BSR20181847 -
California Medicine Feb 1962With local anesthesia for intraocular operations, postoperative agitation, nausea and vomiting are less frequent, which tends to reduce the number of intraocular...
With local anesthesia for intraocular operations, postoperative agitation, nausea and vomiting are less frequent, which tends to reduce the number of intraocular complications. Bleeding is less troublesome, and secretions are better controlled. Fewer cardiac and pulmonary complications occur with local anesthesia. Meperidine hydrochloride (Demerol(R)) and pentobarbital sodium (nembutal) remain drugs of choice in preoperative medication. Lidocaine (Xylocaine(R)), 1 or 2 per cent, is a most satisfactory local anesthetic for intraocular operations. Complete akinesia of the eyelids has been achieved in every instance by a modified combination of the O'Brien and Van Lint techniques, using lidocaine 1 per cent. Nasolacrimal procedures can be performed satisfactorily by injecting the nasociliary and infraorbital nerves with lidocaine 2 per cent.
Topics: Analgesia; Anesthesia; Anesthesia and Analgesia; Anesthesia, Local; Anesthesiology; Anesthetics, Local; Humans; Lidocaine; Meperidine; Ophthalmology; Pain; Pain Management
PubMed: 13918834
DOI: No ID Found -
Journal of Pain and Symptom Management Apr 2014Normeperidine accumulates in patients with impaired renal function and may cause central neurotoxicity. However, some uremic patients still undergo meperidine treatment...
CONTEXT
Normeperidine accumulates in patients with impaired renal function and may cause central neurotoxicity. However, some uremic patients still undergo meperidine treatment for chronic pain.
OBJECTIVES
To prevent normeperidine side effects and complications, we investigated the clearance rate and extraction ratio of meperidine and normeperidine in hemodialysis patients with chronic pain.
METHODS
Three hemodialysis patients, with diagnoses of chronic pancreatitis, chronic back pain, and intractable intra-abdominal pain, received long-term (more than six months) administration of meperidine for chronic noncancer pain. During regular hemodialysis, 72 blood samples in total were collected from the afferent port, efferent port, and ultradiafiltrate port at eight time points. The plasma concentrations of meperidine and normeperidine were determined by high-performance liquid chromatography.
RESULTS
The prehemodialysis plasma concentrations of meperidine and normeperidine were 2963 ± 315 and 2369 ± 1974 ng/mL, which declined to 591 ± 109 and 853 ± 765 ng/mL, with 80% and 65% reduction, respectively. The plasma clearance and extraction ratios of meperidine were 22.7 ± 9.8 mL/minute and 10.1 ± 5.6% and for normeperidine 26.0 ± 11.4 mL/minute and 10.8 ± 2.5%, respectively.
CONCLUSION
Hemodialysis can efficiently remove meperidine and its active metabolite, normeperidine, in uremic patients receiving long-term meperidine therapy for chronic noncancer pain.
Topics: Abdominal Pain; Adult; Analgesics, Opioid; Back Pain; Blood Chemical Analysis; Chromatography, High Pressure Liquid; Chronic Pain; Female; Humans; Male; Meperidine; Metabolic Clearance Rate; Middle Aged; Pancreatitis, Chronic; Renal Dialysis; Time Factors
PubMed: 23870842
DOI: 10.1016/j.jpainsymman.2013.05.007 -
American Journal of Veterinary Research Jul 2001To determine the analgesic, hemodynamic, and respiratory effects induced by caudal epidural administration of meperidine hydrochloride in mares.
OBJECTIVE
To determine the analgesic, hemodynamic, and respiratory effects induced by caudal epidural administration of meperidine hydrochloride in mares.
ANIMALS
7 healthy mares.
PROCEDURE
Each mare received meperidine (5%; 0.8 mg/kg of body weight) or saline (0.9% NaCl) solution via caudal epidural injection on 2 occasions. At least 2 weeks elapsed between treatments. Degree of analgesia in response to noxious electrical, thermal, and skin and muscle prick stimuli was determined before and for 5 hours after treatment. In addition, cardiovascular and respiratory variables were measured and degree of sedation (head position) and ataxia (pelvic limb position) evaluated.
RESULTS
Caudal epidural administration of meperidine induced bilateral analgesia extending from the. coccygeal to S1 dermatomes in standing mares; degree of sedation and ataxia was minimal. Mean (+/- SD) onset of analgesia was 12 +/- 4 minutes after meperidine administration, and duration of analgesia ranged from 240 minutes to the entire 300-minute testing period. Heart and respiratory rates, rectal temperature, arterial blood pressures, Hct, PaO2, PaCO2, pHa, total solids and bicarbonate concentrations, and base excess were not significantly different from baseline values after caudal epidural administration of either meperidine or saline solution.
CONCLUSIONS AND CLINICAL RELEVANCE
Caudal epidural administration of meperidine induced prolonged perineal analgesia in healthy mares. Degree of sedation and ataxia was minimal, and adverse cardiorespiratory effects were not detected. Meperidine may be a useful agent for induction of caudal epidural analgesia in mares undergoing prolonged diagnostic, obstetric, or surgical procedures in the anal and perineal regions.
Topics: Analgesia, Epidural; Analgesics, Opioid; Animals; Ataxia; Female; Hemodynamics; Horses; Injections, Epidural; Meperidine; Pain Measurement; Respiration
PubMed: 11453471
DOI: 10.2460/ajvr.2001.62.1001 -
International Journal of Environmental... Nov 2021Pain relief during labor is a part of standard care in modern obstetrics. Several modalities used for pain relief have their own disadvantages and benefits in terms of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pain relief during labor is a part of standard care in modern obstetrics. Several modalities used for pain relief have their own disadvantages and benefits in terms of side effects, effectiveness, availability, and satisfaction. The objectives of this study are primarily to compare the effectiveness and patients' satisfaction for pain relief during labor between pethidine and inhaled 50% nitrous oxide (Entonox).
METHODS
Laboring women at 37-41 + 6 weeks of gestation were randomly allocated to receive pethidine (50 mg intravenously) or Entonox for reducing labor pain. Pain scores were evaluated at 0, (baseline), 30, 60, 90, and 120 min after initiation, using the visual analog scale (VAS) and also satisfaction score after delivery using the verbal rating scale (VRS). The secondary outcomes were also assessed, including APGAR scores, labor course, side effects, and cesarean section rate.
RESULTS
A total of 136 laboring women underwent randomization into two groups, but only 58 and 65 in the pethidine group and the Entonox group were available for analysis. The median pain scores at baseline, 30, 60, and 90 min were comparable between both groups (-value > 0.05); however, pain score at 120 min in the pethidine group was significantly higher (-value: 0.038). The median of satisfaction score was significantly higher in the Entonox group (4 vs. 3; -value 0.043). All of the secondary outcomes were comparable between the two groups.
CONCLUSIONS
Both have comparable effectiveness, but Entonox has a higher satisfaction score. Entonox could be an alternative to pethidine for reducing labor pain, because of its efficacy, ease for self-adjustment for satisfaction, and no serious effects on the labor course and newborns.
Topics: Analgesics, Opioid; Cesarean Section; Female; Humans; Infant, Newborn; Labor Pain; Meperidine; Nitrous Oxide; Oxygen; Pregnancy
PubMed: 34886299
DOI: 10.3390/ijerph182312571 -
Anesthesiology Feb 1987The experiments examined the characteristics of analgesia produced by different doses of morphine, meperidine (pethidine), fentanyl, and sufentanil after epidural and...
The experiments examined the characteristics of analgesia produced by different doses of morphine, meperidine (pethidine), fentanyl, and sufentanil after epidural and subcutaneous injection in rats. The specificity of the analgesia was also determined; other in vivo pharmacologic activities (i.e., blockade of pinna and cornea reflexes and production of skeletal muscle rigidity) were monitored as pharmacologic indices of opiate drug activity in the brain. After subcutaneous injection, the opiates produced dose-dependent analgesia, blocked the pinna and cornea reflexes, and induced muscle rigidity. After epidural injection, all four compounds produced dose-dependent analgesia and had greater potency, earlier onset, shorter duration, and greater specificity of analgesic action than was the case after subcutaneous injection. Specificity is defined here as the ratio of the ED50 dose that blocked the pinna reflex to the ED50 dose that produced analgesia. The gains in potency and specificity, but not the gains in onset time and the losses in duration of analgesia, differed considerably among the compounds that were examined. The subcutaneous-to-epidural potency ratio related in a linear manner with the lipid-to-water partition coefficient. The gain in specificity also appeared to be related to lipid solubility. The microgram X kg-1 doses at which the opiates produced analgesia in rats correlate well with the potency of these compounds in producing analgesia after epidural injection in humans. The rat epidural preparation reflected the doses, onset, and specificity, but not the duration, of analgesia produced by epidural opiates in humans.
Topics: Analgesia; Animals; Cornea; Fentanyl; Injections, Epidural; Injections, Subcutaneous; Male; Meperidine; Morphine; Rats; Rats, Inbred Strains; Sufentanil; Time Factors
PubMed: 2949676
DOI: 10.1097/00000542-198702000-00013 -
Pain Physician May 2016The optimum dose of dexmedetomidine for shivering control with the least hemodynamic derangements is still under research. (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
The optimum dose of dexmedetomidine for shivering control with the least hemodynamic derangements is still under research.
OBJECTIVE
To compare the efficacy, hemodynamic and side effects of dexmedetomidine in 3 different doses with those of meperidine for the treatment of shivering in patients undergoing spinal anesthesia for minor elective lower abdominal surgery.
STUDY DESIGN
Prospective double-blind randomized clinically controlled study.
SETTING
University hospital.
METHODS
One hundred twenty patients who developed shivering under spinal anesthesia.On shivering, patients were randomly allocated to receive an intravenous 2 mL bolus dose of meperidine 0.4 mg/kg (meperidine group, n = 30), dexmedetomidine 0.5 µg/kg (DEX I group, n = 30), 0.3 µg/kg (DEX II group, n = 30), or 0.2µg/kg (DEX III group, n = 30). Control of shivering, time taken for cessation of shivering, response rate, recurrence, hemodynamic changes, sedation score, tympanic temperature, and side effects were noted and compared between groups.
RESULTS
The groups were comparable regarding demographic profile, tympanic temperature decline, and shivering onset time (P > 0.05). Lower shivering cessation time (P < 0.001) and higher response rate (P < 0.01) were observed in DEX I and II groups compared with DEX III and meperidine groups, with a nonsignificant difference between DEX I and II groups. Recurrence of shivering activity was higher in DEX III group (36.7%, P < 0.01) compared with DEX I (10%), DEX II (6.7%) and meperidine (16.7%) groups. Lower heart rates, systolic and diastolic blood pressure mean values were recorded in DEX I group (P < 0.05). Nine patients (30%) in DEX I group were in levels 3 - 5 of sedation (P < 0.02) compared with 5 (16.66%), 2 (6.66%), and 4 (13.3) patients in DEX II, DEX III, and meperidine groups, respectively.
LIMITATIONS
This study is limited by its small sample size.
CONCLUSIONS
Among the 3 doses investigated, dexmedetomidine 0.3µg/kg effectively treated shivering associated with spinal anesthesia with modest hemodynamic and sedation effects.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02382432.
KEY WORDS
Dexmedetomidine, hypothermia, shivering, spinal anesthesia.
Topics: Adolescent; Adult; Analgesics, Non-Narcotic; Analgesics, Opioid; Anesthesia, Spinal; Dexmedetomidine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Meperidine; Middle Aged; Outcome Assessment, Health Care; Prospective Studies; Shivering; Young Adult
PubMed: 27228512
DOI: No ID Found -
Anesthesiology Jul 1998BACKGROUND. Meperidine (pethidine) reportedly treats postoperative shivering better than equianalgesic doses of other mu-receptor agonists. The authors' first goal was... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
UNLABELLED
BACKGROUND. Meperidine (pethidine) reportedly treats postoperative shivering better than equianalgesic doses of other mu-receptor agonists. The authors' first goal was to develop a method to accurately determine postoperative shivering thresholds, and then to determine the extent to which meperidine and sufentanil inhibit postoperative shivering.
METHODS
A computer-controlled infusion was started before operation in 30 patients, with target plasma concentrations of 0.15, 0.30, or 0.60 microg/ml meperidine or 0.1, 0.15, or 0.2 ng/ ml sufentanil targeted; patients were randomly assigned to each drug and concentration. The infusion was continued throughout surgery and recovery. Anesthesia was maintained with nitrous oxide and isoflurane. Core temperatures were approximately 34 degrees C by the end of surgery. The compensated core temperature at which visible shivering and a 20% decrease in steady-state oxygen consumption was recorded identified the shivering threshold. A blood sample for opioid concentration was obtained from each patient at this time. The ability of each opioid to reduce the shivering threshold was evaluated using linear regression.
RESULTS
End-tidal isoflurane concentrations were <0.2% in each group at the time of extubation, and shivering occurred approximately 1 h later. Meperidine linearly decreased the shivering threshold: threshold (degrees C) = -2.8 x [meperidine (microg/ml)] + 36.2; r2 = 0.64, P = 0.0005. Sufentanil also linearly decreased the shivering threshold: threshold (degrees C) = -7.8 x [sufentanil (ng/ ml)] + 36.9; r2 = 0.46, P = 0.02.
CONCLUSIONS
At a given dose, sufentanil inhibited shivering 2,800 times better than meperidine. However, the equianalgesic ratio of these drugs is approximately 4,900. That is, meperidine inhibited shivering better than would be expected based on the equianalgesic potency ratio. These data are thus consistent with clinical observations suggesting that meperidine indeed possesses special antishivering activity.
Topics: Adult; Analgesics, Opioid; Humans; Infusions, Intravenous; Meperidine; Middle Aged; Orthopedics; Postoperative Complications; Shivering; Sufentanil
PubMed: 9667292
DOI: 10.1097/00000542-199807000-00009 -
Xenobiotica; the Fate of Foreign... Feb 20201. Meperidine is an opioid analgesic that undergoes demethylation to form the neurotoxic metabolite normeperidine. Previous studies indicate that meperidine...
1. Meperidine is an opioid analgesic that undergoes demethylation to form the neurotoxic metabolite normeperidine. Previous studies indicate that meperidine -demethylation is catalyzed by cytochrome P450 2B6 (CYP2B6), CYP3A4, and CYP2C19.2. The purpose of this study was to examine the relative P450 contributions to meperidine -demethylation and to evaluate the effect of polymorphism on normeperidine generation. Experiments were performed using recombinant P450 enzymes, selective chemical inhibitors, enzyme kinetic assays, and correlation analysis with individual -genotyped human liver microsomes.3. The catalytic efficiency (/) for meperidine -demethylation was similar between recombinant CYP2B6 and CYP2C19, but markedly lower by CYP3A4.4. In -genotyped human liver microsomes, normeperidine formation was significantly correlated with CYP2C19 activity (-mephenytoin 4-hydroxylation).5. CYP2C19 inhibitor (+)--3-benzylnirvanol and CYP3A inhibitor ketoconazole significantly reduced microsomal normeperidine generation by an individual donor with high CYP2C19 activity, whereas donors with lower CYP2C19 activity were sensitive to inhibition by ketoconazole but not benzylnirvanol.6. These findings demonstrate that the relative CYP3A4, CYP2B6, and CYP2C19 involvement in meperidine -demethylation depends on the enzyme activities in individual human liver microsomal samples. CYP2C19 is likely an important contributor to normeperidine generation in individuals with high CYP2C19 activity, but additional factors influence inter-individual metabolite accumulation.
Topics: Cholinesterase Inhibitors; Cytochrome P-450 CYP2C19; Cytochrome P-450 Enzyme System; Demethylation; Humans; Meperidine; Mephenytoin
PubMed: 30902024
DOI: 10.1080/00498254.2019.1599465