Design, synthesis, and pharmacological evaluation of ultrashort- to long-acting opioid analgesics

Feldman, Paul L.; James, McKerrow; Brackeen, Marcus; Bilotta, Joanne; Schuster, Sascha; Lahey, A P; Lutz, Michael W.; Johnson, Martin P.; Leighton, H J

doi:10.1021/jm00111a041

Cited by 186 publications

(80 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recall that fentanyl's termination of action is dependent upon redistribution and liver metabolism. Remifentanil's termination of action is accomplished by nonspecific blood esterases (Feldman, et al, 1991). This is similar to esmolol, a selective Β 1 antagonist (Lowenthal, et al, 1985).…”

Section: Remifentanilmentioning

confidence: 97%

“…Fentanyl is a phenylpiperidine µ-selective (mu-selective) opioid (Feldman, et al, 1991). Remifentanil is also a phenylpiperidine µ-selective opioid (Amin, et al, 1993;James, et al, 1991).…”

Section: Balanced Anesthesiamentioning

confidence: 99%

“…Remifentanil is also a phenylpiperidine µ-selective opioid (Amin, et al, 1993;James, et al, 1991). The term "µ-selective opioid" refers to a drug that has a high affinity for the µ-opioid receptors found throughout the neuroaxis and periphery.…”

Section: Balanced Anesthesiamentioning

confidence: 99%

See 2 more Smart Citations

Psychomotor Functioning: Comparison of Patients Recovering From General Anesthesia With Remifentanil and a Volatile Anesthetic Versus Fentanyl and a Volatile Anesthetic

Moseley¹

1998

View full text Add to dashboard Cite

Report Documentation PageForm Public reporting burden for the collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. REPORT DATE OCT 1998

show abstract

Section: Remifentanilmentioning

confidence: 97%

Section: Balanced Anesthesiamentioning

confidence: 99%

See 1 more Smart Citation

Psychomotor Functioning: Comparison of Patients Recovering From General Anesthesia With Remifentanil and a Volatile Anesthetic Versus Fentanyl and a Volatile Anesthetic

Moseley¹

1998

View full text Add to dashboard Cite

show abstract

“…Remifentanil is an ultra-short-acting agent with a context-sensitive half-time of approximately 3 minutes (FELDMAN et al, 1991;WESTMORELAND et al, 1993). Remifentanil differs from other opioid drugs in that it possesses an ester linkage that allows it to be broken down by plasma cholinesterases, resulting in reasonably predictable pharmacokinetics.…”

Section: Introductionmentioning

confidence: 99%

Avaliação da concentração expirada de isoflurano em infusão continua de remifentanil em cadelas submetidas a mastectomia

et al. 2015

View full text Add to dashboard Cite

The aims of this study were to evaluate the effects of two constant rate infusions of remifentanil on end tidal isoflurane (ETiso) in dogs undergoing mastectomy surgery. Eighteen bitches, 12+2 years of age, weighing 15+5 Kg were randomized into 3 groups (n=6/group) and underwent unilateral mastectomy due to mammary neoplasia. All animals received the premedications of morphine (0.5 mg Kg -1 ) and acepromazine (0.03 mg Kg -1 ) by intramuscular route (IM). Propofol dose-effect was used for induction of anesthesia. The animals were intubated and connected to a circle breathing system, and IPPV (intermittent positive pressure ventilation) was used to maintain normocapnia with an oxygen flow rate of 2 L/min and FiO 2 100%. Anesthesia was maintained with isoflurane and saline solution (control group [GCON], n=6) or intravenous infusion of remifentanil at a rate of 0.15 µg Kg -1 min -1 (REMI 0.15 n=6) or 0.3 µg Kg -1 min -1 (REMI 0.3 n=6). Cardiopulmonary variables and ETiso were monitored before and every 15 minutes after the start of surgery. The data were analyzed by ANOVA with multiple repetitions between moments and ANOVA followed by the Student Newman Keuls test (≤0.05) for comparisons between groups. Heart rate was lower at all moments in the REMI 0.15 and REMI 0.3 groups than in the GCON, and heart rate was not significantly different between the two remifentanil infusion groups. Additionally, the arterial blood pressure values (SAP, MAP and DAP) were not different between all groups. Baseline values (before surgery) of ETiso were not different between the 3 groups. After the start of surgery, ETiso ranged from 1.37±0.3 to 1.05±0.19 in the control group; in the REMI 0.15 and REMI 0.3 groups, ETiso was 36.5% and 65.7% lower than in the control group (M15). Remifentanil infusion reduced ETiso in a dose-dependent manner in animals undergoing radical mastectomy without causing significant cardiopulmonary alterations. Key words: Dogs, mastectomy, remifentanil, isoflurane ResumoOs objetivos deste estudo são a avaliação dos efeitos de duas taxas fixas de infusão continua de remifentanil na concentração expirada de isoflurano (ETiso) em cadelas submetidas à mastectomia. aleatoriamente em 3 grupos (n=6/grupo) e submetidos à mastectomia unilateral devido a neoplasia mamária. Todos os animais foram pré-medicados com morfina (0,5 mg Kg -1 ) e acepromazina (0,03 mg Kg -1 ), ambas por via intramuscular (IM). A indução da anestesia foi realizada com propofol (doseefeito). Os animais foram intubados e conectados a um sistema circular com reinalação de gases. Foi utilizada ventilação com pressão positiva intermitente para manutenção de normocapnia com fluxo de oxigênio de 2 L/min e FiO 2 de 100%. A anestesia foi mantida com isoflurano e solução salina (grupo controle [GCON], n=6) ou infusão intravenosa de remifentanil na taxa de 0,15 µg Kg -1 min -1 (REMI 0,15 n=6) ou 0,3 µg Kg -1 min -1 (REMI 0,3 n=6). As variáveis cardiovasculares e a ETiso foram monitoradas antes e a cada 15 minutos após o início da cirurgia. Os dado...

show abstract

“…For example, remifentanil has an ultra-short half-life of several minutes (Egan et al, 1993) because of its rapid metabolism by blood and tissue esterases (Feldman et al, 1991). Most clinically used opioids, including fentanyl and morphine, have half-lives in the range of hours (Trescot et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Distinct Mechanisms Underlying Pronociceptive Effects of Opioids

Heinl¹,

Drdla-Schutting²,

Xanthos³

et al. 2011

J. Neurosci.

View full text Add to dashboard Cite

In addition to analgesia, opioids may also produce paradoxical pain amplification [opioid-induced hyperalgesia (OIH)] either on abrupt withdrawal or during continuous long-term application. Here, we assessed antinociceptive and pronociceptive effects of three clinically used opioids at C-fiber synapses in the rat spinal dorsal horn in vivo. During 60 min of intravenous infusions of remifentanil (450), C-fiber-evoked field potentials were depressed and pairedpulse ratios (PPR) were increased, indicating a presynaptic inhibition by all three opioids. After withdrawal, postsynaptic responses were enhanced substantially for the remaining of the recording periods of at least 3 h. Withdrawal from remifentanil led to long-term potentiation (LTP) of synaptic strength in C-fibers via activation of spinal -opioid receptors (MORs) and spinal NMDA receptors (NMDARs). Fentanyl and morphine caused an enhancement of synaptic transmission at C-fibers, which involved two distinct mechanisms: (1) an opioid withdrawal LTP that also required activation of spinal MORs and NMDARs and that was associated with a decrease in PPR suggestive of a presynaptic mechanism of its expression, and (2) an immediate-onset, descending facilitation of C-fiber-evoked field potentials during and after intravenous infusion of fentanyl and morphine. Immediate-onset, descending facilitation was mediated by the activation of extraspinal MORs, descending serotonergic pathways, and spinal 5-hydroxytryptamine-3 receptors (5-HT 3 Rs). Our study identified fundamentally different pronociceptive effects of clinically used opioids and suggests that OIH can be prevented by the combined use of NMDAR and 5-HT 3 R antagonists.

show abstract

Design, synthesis, and pharmacological evaluation of ultrashort- to long-acting opioid analgesics

Cited by 186 publications

References 1 publication

Psychomotor Functioning: Comparison of Patients Recovering From General Anesthesia With Remifentanil and a Volatile Anesthetic Versus Fentanyl and a Volatile Anesthetic

Psychomotor Functioning: Comparison of Patients Recovering From General Anesthesia With Remifentanil and a Volatile Anesthetic Versus Fentanyl and a Volatile Anesthetic

Avaliação da concentração expirada de isoflurano em infusão continua de remifentanil em cadelas submetidas a mastectomia

Distinct Mechanisms Underlying Pronociceptive Effects of Opioids

Contact Info

Product

Resources

About