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Synthesis and SAR study of Meperidine Analogues as Selective Serotonin Reuptake Inhibitors (SSRIs)Gu, Xiaobo 14 May 2010 (has links)
Meperidine has been shown to have potent binding affinity for serotonin transporters (SERT) (Ki = 41 nM) and be an inhibitor of serotonin reuptake. Based upon these pharmacological results meperidine has been identified as a lead compound for the development of a novel class of serotonin-selective reuptake inhibitors (SSRIs). A variety of potent analogues of meperidine have been synthesized and evaluated in vitro as potential ligands for the serotonin transporter. Substitutions have been made on the aryl ring, the ester moiety and the piperidine nitrogen of meperidine. Potent analogues of the aryl substituted series that included 4-iodophenyl, 2-naphthyl, 3,4-dichlorophenyl and 4-biphenyl meperidine derivatives were synthesized and chosen for further optimization of the benzyl ester analogues. Benzyl ester analogues included 4-nitro, 4-methoxyl and 3,4-dichloro benzyl analogues and exhibited high potency for serotonin transporters and high selectivity over the dopamine transporter (DAT) and the norepinephrine transporter (NET). Also the N-demethylated analogues improve the binding affinity and selectivity for serotonin transporter. The analogue 4- (carboxymethoxybenzyl)-4-(4-iodophenyl) piperidine (69f), was found the most potent (Ki=0.6 nM) and selective ligand for serotonin transporter (DAT/SERT >4500; NET/SERT >4500) for the series and has been advanced to in vivo evaluation.
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Liquid chromatography-mass spectrometry as a tool for drug metabolite identification in biological fluids : with application to Ketobemidone /Sundström, Ingela, January 2007 (has links)
Diss. (sammanfattning) Uppsala : Uppsala universitet, 2007. / Härtill 4 uppsatser.
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A double-blind comparison of nalbuphine hydrochloride and meperidine hydrochloride as intravenous analgesics in combination with diazepam for use in oral surgery patients a thesis submitted in partial fulfillment ... oral and maxillofacial surgery /Scott, Richard F. January 1982 (has links)
Thesis (M.S.)--University of Michigan, 1982.
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A double-blind comparison of nalbuphine hydrochloride and meperidine hydrochloride as intravenous analgesics in combination with diazepam for use in oral surgery patients a thesis submitted in partial fulfillment ... oral and maxillofacial surgery /Scott, Richard F. January 1982 (has links)
Thesis (M.S.)--University of Michigan, 1982.
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GENETIC VARIATIONS OF CYP2B6 ENZYME AND THE RESPONSE TO MEPERIDINE IN ORAL SEDATIONHua, Sally 14 April 2009 (has links)
Purpose: The purpose of this study was to determine the relationship of CYP2B6 genotype to the clinical response to meperidine in pediatric dental patients. Methods: Twenty-five patients, ASA I/ II, 45–92 months old, received an oral sedative regimen containing meperidine for dental treatment. The North Carolina Behavior Rating Scale (NCBRS) and Overall Effectiveness of Sedation Scale (OESS) were used to assess their behavior and sedation outcome. Saliva DNA samples were genotyped by PCR-RFLP. Results: We found the following genotype distributions: homozygous wild-type 1*1 (n = 8, 32%), heterozygous 1*6 (n = 13, 52%), and homozygous variant 6*6 (n = 4, 16%). The genotypes were predictive of a significant decrease in the overall effectiveness of sedation. Conclusion: Variation in CYP2B6 appears to be predictive of less successful sedations; wild-type individuals experienced more successful sedations than the homozygous variant 6*6. Future research regarding the enzyme kinetics of meperidine is needed to determine the exact enzymatic function of CYP2B6 and its variants.
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Comparison of Triple Combination Oral Sedation Regimens for Pediatric Dental TreatmentHenderson, Brett H 01 January 2019 (has links)
Purpose: Compare the efficacy of two benzodiazepines (diazepam or midazolam) in combination with meperidine and hydroxyzine for pediatric dental sedation. Methods: A randomized, double blind observation study of behaviors and outcomes related to two sedation groups. Frankl and Houpt behavior scores were recorded at three time points: injection time, initiation of treatment and at the end of treatment. Postoperative phone call surveys were conducted within eight hours of discharge to assess sleep, activity, and behavior. Results: A total of 40 sedation subjects were included in the study, of which 20 were treated with diazepam triple Combination (Di+M+H) and 20 with midazolam triple regime (Mi+M+H). Treatment was successful for 45% of cases with midazolam and 70% with diazepam (P value=.20). Houpt sleep scores were significantly higher for diazepam than midazolam at injection (P-value=.0043) and during treatment (P-value=.0152). Although Frankl scores, Houpt move and Houpt cry scores tended to favor diazepam, none were statistically significantly different. More abnormal behavior was reported with midazolam, though not statistically significant (35% vs 6%, P-value=.0854). Postoperative sleep time was longer for midazolam, but not significantly different (median sleep time: 61 vs 45 minutes, P-value=.2071). Conclusion: The diazepam, meperidine, hydroxyzine triple combination sedation regimen shows promising results as a successful alternative to midazolam triple combination. Longer postoperative monitoring may be required with diazepam, but this study has shown postoperative sleep times to be less than previously reported. Larger sample size is needed to determine if the current trend will be maintained.
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Conscious Sedation of the pediatric dental patient: a comparison of meperidine versus butorphanolGuthrie, Andrew C. (Andrew Cleveland), 1969- January 2001 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / Treating pediatric dental patients four years old and younger can be difficult at
times due to patient behavior. Conscious sedation has been employed as a means to
control pediatric dental patients for several years. Butorphanol tartrate has been used
safely for pain control in pediatric patients for several years, but has never been used for
sedating pediatric dental patients. The purpose of this study is to compare the behavioral
and physiologic effects of conscious sedation on pediatric dental patients using
intramuscular meperidine and an equipotent dosage of intramuscular butorphanol. Forty
conscious sedations of ASA I pediatric dental patients between the ages of 13 and 60
months were accomplished using either 2.0 mg/kg of intramuscular meperidine or 0.03
mg/kg of intramuscular butorphanol. Each sedation was videotaped and three viewers
viewed the videotapes rating them with a computer program (ACS) involving a four-code
behavior rating scale. The tlrree viewers rated patient behavior for each sedation also
with a form with global rating, categorical, and dichotomous scales. Physiologic signs of
oxygen saturation, blood pressure, heart rate, and respiration rate were monitored at
baseline and every 5 minutes during treatment. The operator also rated the sedation
patient behavior with a form that had pre-treatment Frankl, post-treatment Frankl, global
rating categorical, dichotomous, and sedation success rating scales. The two groups
demographic data, physiologic data, ACS data, the three viewer's behavior rating form,
and the operator's behavior rating form were analyzed for any statistically significant
differences between the groups. The statistical analysis of the demographic data revealed
a statistically significant trend in the butorphanol group toward extractions. The
meperidine group had a statistically significant higher mean oxygen saturation during
treatment (99.63 percent) than the butorphanol group (99.20 percent). The butorphanol
group spent significantly more time in the annoyed ACS behavior rating code and showed
a trend toward less time spent in the quiet ACS behavior rating code. There were no
statistically significant differences in the three viewers ratings of global rating,
categorical, and dichotomous scales. The operators' ratings showed the meperidine group
had a statistically significant better global rating than the butorphanol group. Overall
butorphanol appears to be equal clinically to meperidine in physiologic effects and patient
behavior effects. No adverse effects occurred with either medication. Butorphanol may
be offered as an alternative sedative agent to other narcotic sedative agents with more side effects.
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A Comparison of Moderate Oral Sedation Drug Regimens for Pediatric Dental Treatment: A Pilot StudyParikh, Ojas A 01 January 2017 (has links)
Purpose: Compare moderate oral sedation of pediatric patients using Hydroxyzine and Meperidine with either Diazepam or Midazolam in management of pediatric dental patients.
Methods: Randomized, double-blind, crossover pilot study of patients 3 to 7 years of age requiring two sedation visits. Frankl and Houpt behavior scores recorded at injection time, initiation of treatment and 100% oxygen at end of treatment. Postoperative phone call surveys conducted within eight hours and within 24 hours of discharge. Wilcoxon Signed-Rank tests, Fisher’s Exact Chi-squared test and 0.10 significance level.
Results: 25 subjects completed 35 sedations. Eight participants completed both treatments and demonstrated significantly higher total Houpt Scores with Diazepam at all treatment stages. Frankl scores favored Diazepam at injection time. More abnormal behavior was found with Midazolam, less memory of the visit with Diazepam, but longer sleep time with Diazepam.
Conclusions: Sedation with the Hydroxyzine, Meperidine and Diazepam regimen may allow for a better overall sedation experience. Postoperative monitoring is essential. The results are promising and demonstrate the value of a larger study on sedation with Diazepam.
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