Analgesic effects of Sazetidine-A, a new nicotinic cholinergic drug.

Abstract:

BACKGROUND:The use of nicotinic agonists for analgesia is limited by their unacceptable side effects. Sazetidine-A is a new partial agonist nicotinic ligand that has very high selectivity for beta2-containing nicotinic acetylcholine receptors. It potently and selectively desensitizes alpha4beta2 nicotinic acetylcholine receptors without measurable effects on alpha3beta4 receptors. The authors investigated the analgesic effects of Sazetidine-A using the formalin model of chronic inflammatory pain. METHODS:The formalin test was conducted after rats received intraperitoneal saline, Sazetidine-A (0.125, 0.25, 0.5, 1, 2 mg/kg), or subcutaneous epibatidine (2.5-5-10 mug/kg). In other experiments, Sazetidine-A was preceded by naloxone (0.5 mg/kg) or mecamylamine (10 mg). Effects of Sazetidine-A and epibatidine on locomotor were tested in an open field, and seizure activity was measured using the Racine scale. Locus coeruleus neuron extracellular single-unit spontaneous discharge was recorded in anesthetized animals after Sazetidine-A and epibatidine. RESULTS:Higher doses of Sazetidine-A (0.5, 1, or 2 mg/kg) induced analgesia, with pain scores significantly lower than those seen after saline, lower doses of Sazetidine-A, and epibatidine (P < 0.001). Naloxone did not antagonize the effects of Sazetidine-A, and mecamylamine had partial, dose-dependent antagonistic effects. Epibatidine excited locus coeruleus neurons, whereas Sazetidine-A had no effect on these neurons. Epibatidine and Sazetidine-A affected animals' locomotor activity for the initial 20 min. While analgesic doses of epibatidine caused seizures, no seizure activity or other neurologic complications were seen in animals that received as much as four times the minimum analgesic dose of Sazetidine-A. CONCLUSIONS:Sazetidine-A seems to be a potent analgesic without causing neurologic side effects.

journal_name

Anesthesiology

journal_title

Anesthesiology

authors

Cucchiaro G,Xiao Y,Gonzalez-Sulser A,Kellar KJ

doi

10.1097/ALN.0b013e3181834490

subject

Has Abstract

pub_date

2008-09-01 00:00:00

pages

512-9

issue

3

eissn

0003-3022

issn

1528-1175

pii

00000542-200809000-00022

journal_volume

109

pub_type

杂志文章
  • Pulmonary uptake of propofol in cats. Effect of fentanyl and halothane.

    abstract:BACKGROUND:Many drugs are removed by the lung. The pulmonary uptake of one drug can be inhibited when a second, highly accumulated drug is administered parenterally or as a chronic oral treatment. The effect of inhalational anesthetics on pulmonary drug uptake has not been extensively studied and may alter pharmacokine...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-199306000-00021

    authors: Matot I,Neely CF,Katz RY,Neufeld GR

    更新日期:1993-06-01 00:00:00

  • The American Society of Anesthesiologists Postoperative Visual Loss Registry: analysis of 93 spine surgery cases with postoperative visual loss.

    abstract:BACKGROUND:Postoperative visual loss after prone spine surgery is increasingly reported in association with ischemic optic neuropathy, but its etiology is unknown. METHODS:To describe the clinical characteristics of these patients, the authors analyzed a retrospectively collected series of 93 spine surgery cases volun...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-200610000-00007

    authors: Lee LA,Roth S,Posner KL,Cheney FW,Caplan RA,Newman NJ,Domino KB

    更新日期:2006-10-01 00:00:00

  • Lack of nonshivering thermogenesis in infants anesthetized with fentanyl and propofol.

    abstract:BACKGROUND:Sweating, vasoconstriction, and shivering have been observed during general anesthesia. Among these, vasoconstriction is especially important because-once triggered-it minimizes further hypothermia. Surprisingly, the core-temperature plateau associated with vasoconstriction appears to preserve core temperatu...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-199704000-00006

    authors: Plattner O,Semsroth M,Sessler DI,Papousek A,Klasen C,Wagner O

    更新日期:1997-04-01 00:00:00

  • High-frequency, small-volume ventilation during thoracic surgery.

    abstract::Surgical conditions during conventional mechanical ventilation (CMV) and pulmonary gas exchange were compared with those during high-frequency ventilation (HFV) in 24 patients undergoing anesthesia for intrathoracic surgery. HFV at an oscillatory frequency of 3 Hz and a delivered gas volume of 1.3-1.9 ml/kg provided e...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-198602000-00014

    authors: Glenski JA,Crawford M,Rehder K

    更新日期:1986-02-01 00:00:00

  • Pontine cholinergic mechanisms modulate the cortical electroencephalographic spindles of halothane anesthesia.

    abstract:BACKGROUND:Halothane anesthesia causes spindles in the electroencephalogram (EEG), but the cellular and molecular mechanisms generating these spindles remain incompletely understood. The current study tested the hypothesis that halothane-induced EEG spindles are regulated, in part, by pontine cholinergic mechanisms. M...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-199604000-00023

    authors: Keifer JC,Baghdoyan HA,Lydic R

    更新日期:1996-04-01 00:00:00

  • The effect of 30% nitrous oxide on thermoregulatory responses in humans during hypothermia.

    abstract::Clinical studies have reported that body core temperature decreases during prolonged surgery and anesthesia. Although this finding has been attributed primarily to increased heat loss resulting from exposure of body cavities and infusion of cold solutions, it is generally recognized that anesthesia interferes with the...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-199204000-00011

    authors: Passias TC,Mekjavić IB,Eiken O

    更新日期:1992-04-01 00:00:00

  • Performance of noninvasive partial CO2 rebreathing cardiac output and continuous thermodilution cardiac output in patients undergoing aortic reconstruction surgery.

    abstract:BACKGROUND:In the partial CO(2) rebreathing method, monitored changes in CO(2) elimination and end-tidal CO(2) in response to a brief rebreathing period are used to estimate cardiac output. However, dynamic changes in CO(2) production during ischemia and reperfusion may affect the accuracy of these estimates. This stud...

    journal_title:Anesthesiology

    pub_type: 临床试验,杂志文章

    doi:10.1097/00000542-200308000-00009

    authors: Kotake Y,Moriyama K,Innami Y,Shimizu H,Ueda T,Morisaki H,Takeda J

    更新日期:2003-08-01 00:00:00

  • Shannon entropy applied to the measurement of the electroencephalographic effects of desflurane.

    abstract:BACKGROUND:The Shannon entropy is a standard measure for the order state of sequences. It quantifies the degree of skew of the distribution of values. Increasing hypnotic drug concentrations increase electroencephalographic amplitude. The probability density function of the amplitude values broadens and flattens, there...

    journal_title:Anesthesiology

    pub_type: 临床试验,杂志文章

    doi:10.1097/00000542-200107000-00010

    authors: Bruhn J,Lehmann LE,Röpcke H,Bouillon TW,Hoeft A

    更新日期:2001-07-01 00:00:00

  • A phase III, double-blind, placebo-controlled, multicenter study on the efficacy of recombinant human antithrombin in heparin-resistant patients scheduled to undergo cardiac surgery necessitating cardiopulmonary bypass.

    abstract:BACKGROUND:The study evaluated the efficacy of recombinant human antithrombin (rhAT) for restoring heparin responsiveness in heparin resistant patients undergoing cardiac surgery. METHODS:This was a multicenter, randomized, double-blind, placebo-controlled study in heparin-resistant patients undergoing cardiac surgery...

    journal_title:Anesthesiology

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1097/00000542-200502000-00007

    authors: Avidan MS,Levy JH,Scholz J,Delphin E,Rosseel PM,Howie MB,Gratz I,Bush CR,Skubas N,Aldea GS,Licina M,Bonfiglio LJ,Kajdasz DK,Ott E,Despotis GJ

    更新日期:2005-02-01 00:00:00

  • Effect of diltiazem on midazolam and alfentanil disposition in patients undergoing coronary artery bypass grafting.

    abstract:BACKGROUND:Midazolam and alfentanil are desirable anesthetic adjuncts for cardiac anesthesia. They are metabolized by cytochrome P450 3A (CYP3A) enzymes. These isozymes are inhibited by concurrent medications, including the calcium channel antagonist diltiazem, which may have an effect on recovery from anesthesia. MET...

    journal_title:Anesthesiology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00000542-199612000-00004

    authors: Ahonen J,Olkkola KT,Salmenperä M,Hynynen M,Neuvonen PJ

    更新日期:1996-12-01 00:00:00

  • The effects of epidural morphine on cardiac and renal sympathetic nerve activity in alpha-chloralose-anesthetized cats.

    abstract:BACKGROUND:Epidural morphine yields postoperative pain relief and hemodynamic stability. However, the effects of epidural morphine on sympathetic tone are unclear. This study was designed to elucidate the effects of epidural morphine on cardiac (CSNA) and renal (RSNA) sympathetic nerve activity by direct measurement in...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-199806000-00020

    authors: Mori T,Nishikawa K,Terai T,Yukioka H,Asada A

    更新日期:1998-06-01 00:00:00

  • Adaptive support ventilation: an appropriate mechanical ventilation strategy for acute respiratory distress syndrome?

    abstract:BACKGROUND:Adaptive support ventilation (ASV) allows the clinician to set a maximum plateau pressure (PP) and automatically adjusts tidal volume to keep PP below the set maximum. METHODS:ASV was compared to a fixed tidal volume of 6 ml/kg. ASV determined the respiratory rate and tidal volume based on its algorithms. M...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/ALN.0b013e3181b55f8f

    authors: Sulemanji D,Marchese A,Garbarini P,Wysocki M,Kacmarek RM

    更新日期:2009-10-01 00:00:00

  • The detrimental effects of prolonged hypothermia and rewarming in the dog.

    abstract::The authors had previously observed a deleterious cerebrovascular effect of prolonged hypothermia in primates and cats. In this study they examined the systemic as well as cerebral hemodynamic and metabolic effects of 24 hours of hypothermia in the dog. With decreases in temperature to 29 C, cardiac output (Q) and who...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-198003000-00007

    authors: Steen PA,Milde JH,Michenfelder JD

    更新日期:1980-03-01 00:00:00

  • Hypothermic modulation of cerebral ischemic injury during cardiopulmonary bypass in pigs.

    abstract:BACKGROUND:The aim of this study was to determine whether progressive levels of hypothermia (37, 34, 31, or 28 degrees C) during cardiopulmonary bypass (CPB) in pigs reduce the physiologic and metabolic consequences of global cerebral ischemia. METHODS:Sagittal sinus and cortical microdialysis catheters were inserted ...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-199802000-00018

    authors: Conroy BP,Lin CY,Jenkins LW,DeWitt DS,Zornow MH,Uchida T,Johnston WE

    更新日期:1998-02-01 00:00:00

  • Kinetic modulation of HERG potassium channels by the volatile anesthetic halothane.

    abstract:BACKGROUND:(human ether-a-gogo related gene) encodes the cardiac rapidly activating delayed rectifier potassium currents (I(kr)), which play an important role in cardiac action potential repolarization. General anesthetics, like halothane, can prolong Q-T interval, suggesting that they act on myocellular repolarization...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-200210000-00026

    authors: Li J,Correa AM

    更新日期:2002-10-01 00:00:00

  • Determinants of the sensitivity of AMPA receptors to xenon.

    abstract:BACKGROUND:There is substantial and growing literature on the actions of general anesthetics on a variety of neurotransmitter-gated ion channels, with the greatest attention being focused on inhibitory gamma-amino butyric acid type A receptors. In contrast, glutamate receptors, the most important class of fast excitato...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-200402000-00025

    authors: Plested AJ,Wildman SS,Lieb WR,Franks NP

    更新日期:2004-02-01 00:00:00

  • Chronic pain management: American Society of Anesthesiologists Closed Claims Project.

    abstract:BACKGROUND:The practice of chronic pain management has grown steadily in recent years. The purpose of this study was to identify and describe issues and trends in liability related to chronic pain management by anesthesiologists. METHODS:Data from 5,475 claims in the American Society of Anesthesiologists Closed Claims...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-200401000-00018

    authors: Fitzgibbon DR,Posner KL,Domino KB,Caplan RA,Lee LA,Cheney FW,American Society of Anesthesiologists.

    更新日期:2004-01-01 00:00:00

  • Intrathecal sufentanil for labor analgesia does not cause a sympathectomy.

    abstract:BACKGROUND:Intrathecal sufentanil (ITS) is frequently used to provide analgesia during labor. Decreases in blood pressure and sensory changes in this circumstance suggest that ITS may have a local anesthetic effect and thus cause a sympathectomy. To determine whether ITS given to laboring women causes a sympathectomy, ...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-199710000-00022

    authors: Riley ET,Walker D,Hamilton CL,Cohen SE

    更新日期:1997-10-01 00:00:00

  • Neutrophil elastase inhibitor, ONO-5046, modulates acid-induced lung and systemic injury in rabbits.

    abstract:BACKGROUND:Acid instillation leads to direct lung and to secondary systemic organ injury, probably via activated macrophages and neutrophils. This study investigated the effects of neutrophil elastase on organ injury after unilateral lung acid instillation by administrating a specific neutrophil elastase inhibitor, ONO...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-199709000-00025

    authors: Kaneko K,Kudoh I,Hattori S,Yamada H,Ohara M,Wiener-Kronish J,Okumura F

    更新日期:1997-09-01 00:00:00

  • Endothelial glycocalyx as an additional barrier determining extravasation of 6% hydroxyethyl starch or 5% albumin solutions in the coronary vascular bed.

    abstract:BACKGROUND:The impact on the endothelial glycocalyx for the extravasation of colloidal infusion solutions has not been investigated sufficiently. METHODS:Isolated guinea pig hearts were perfused with Krebs-Henseleit buffer in a Langendorff mode. Solutions of 0.9% saline, 5% albumin (70 kd), or 6% hydroxyethyl starch (...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-200405000-00025

    authors: Rehm M,Zahler S,Lötsch M,Welsch U,Conzen P,Jacob M,Becker BF

    更新日期:2004-05-01 00:00:00

  • The neurologic and adaptive capacity score is not a reliable method of newborn evaluation.

    abstract:BACKGROUND:The Neurologic and Adaptive Capacity Score (NACS) is a multi-item scale that was published in 1982 to measure the effects of intrapartum drugs on the neonate. Although this scoring system has been widely used in obstetric anesthesia research, studies confirming its reliability have not been published. The pu...

    journal_title:Anesthesiology

    pub_type: 临床试验,杂志文章

    doi:10.1097/00000542-200106000-00007

    authors: Halpern SH,Littleford JA,Brockhurst NJ,Youngs PJ,Malik N,Owen HC

    更新日期:2001-06-01 00:00:00

  • Relationship between oxygen uptake and mixed venous oxygen saturation in the immediate postoperative period.

    abstract:BACKGROUND:During muscular exercise, a negative correlation has been demonstrated between the value of mixed venous oxygen saturation (SvO2) and the level of muscular work, expressed at each level as the ratio of oxygen uptake (VO2) to each subject's maximal oxygen uptake (VO2max). Because the immediate postoperative p...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-199402000-00007

    authors: Viale JP,Annat G,Lehot JJ,Quard S,Quintin L,Parlow J,Durand PG,Zabot JM,Villard J,Estanove S

    更新日期:1994-02-01 00:00:00

  • 5-HT1A receptor agonist Befiradol reduces fentanyl-induced respiratory depression, analgesia, and sedation in rats.

    abstract:BACKGROUND:There is an unmet clinical need to develop a pharmacological therapy to counter opioid-induced respiratory depression without interfering with analgesia or behavior. Several studies have demonstrated that 5-HT1A receptor agonists alleviate opioid-induced respiratory depression in rodent models. However, ther...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/ALN.0000000000000490

    authors: Ren J,Ding X,Greer JJ

    更新日期:2015-02-01 00:00:00

  • Exogenous ethyl pyruvate versus pyruvate during metabolic recovery after oxidative stress in neonatal rat cerebrocortical slices.

    abstract:BACKGROUND:Exogenous pyruvate and ethyl pyruvate (EP), the key ingredient in a new Ringer's solution in clinical trials, are antioxidants as well as metabolic substrates. In vivo studies show both to be protective in oxidative stress, with EP being better. The authors used an acute rat brain slice preparation to compar...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/01.anes.0000281898.01966.1e

    authors: Zeng J,Liu J,Yang GY,Kelly MJ,James TL,Litt L

    更新日期:2007-10-01 00:00:00

  • Alterations in spectral characteristics of heart rate variability as a correlate of cardiac autonomic dysfunction after esophagectomy or pulmonary resection.

    abstract:BACKGROUND:Both esophagectomy and pulmonary resection are associated with postoperative cardiac complications, partly because of autonomic perturbations involving the heart. This study was undertaken to determine whether heart rate variability (HRV), employed as an index of cardiac autonomic function, changes in patien...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-199605000-00008

    authors: Kimura T,Komatsu T,Takezawa J,Shimada Y

    更新日期:1996-05-01 00:00:00

  • Pentobarbital enhances GABAergic neurotransmission to cardiac parasympathetic neurons, which is prevented by expression of GABA(A) epsilon subunit.

    abstract:BACKGROUND:Pentobarbital decreases the gain of the baroreceptor reflex on the order of 50%, and this blunting is caused nearly entirely by decreasing cardioinhibitory parasympathetic activity. The most likely site of action of pentobarbital is the gamma-aminobutyric acid type A (GABA(A)) receptor. The authors tested wh...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-200209000-00027

    authors: Irnaten M,Walwyn WM,Wang J,Venkatesan P,Evans C,Chang KS,Andresen MC,Hales TG,Mendelowitz D

    更新日期:2002-09-01 00:00:00

  • Ideal permissive hypotension to resuscitate uncontrolled hemorrhagic shock and the tolerance time in rats.

    abstract:BACKGROUND:Studies have shown that permissive hypotension for uncontrolled hemorrhagic shock can result in good resuscitation outcome. The ideal target mean arterial pressure (MAP) and the tolerance time for permissive hypotension have not been determined. METHODS:To elucidate the ideal target MAP and tolerance time f...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/ALN.0b013e3181fe3fe7

    authors: Li T,Zhu Y,Hu Y,Li L,Diao Y,Tang J,Liu L

    更新日期:2011-01-01 00:00:00

  • Interaction of isoflurane with the dopamine transporter.

    abstract:BACKGROUND:Isoflurane administration is known to increase extracellular dopamine (DA) concentration. Because the dopamine transporter (DAT) is a key regulator of DA, it is likely affected by isoflurane. This study investigates the hypothesis that isoflurane inhibits DA reuptake by causing DAT to be trafficked into the ...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-200302000-00021

    authors: Votaw J,Byas-Smith M,Hua J,Voll R,Martarello L,Levey AI,Bowman FD,Goodman M

    更新日期:2003-02-01 00:00:00

  • Respiratory, laryngeal, and tracheal responses to nasal insufflation of volatile anesthetics in anesthetized humans.

    abstract::In order to determine whether or not irritation of the nasal passage with commonly used volatile anesthetics can elicit airway reflexes, we investigated respiratory, laryngeal, and tracheal responses to nasal insufflation of three volatile anesthetics (enflurane, isoflurane, and halothane) in 13 patients anesthetized ...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-199109000-00010

    authors: Nishino T,Tanaka A,Ishikawa T,Hiraga K

    更新日期:1991-09-01 00:00:00

  • Enhancement by propofol of the gamma-aminobutyric acidA response in dissociated hippocampal pyramidal neurons of the rat.

    abstract:BACKGROUND:Activation of the gamma-aminobutyric acidA (GABAA) receptor-ionophore complex has been reported as a possible molecular mechanism of the anesthetic action of propofol. Augmentation of GABA-induced inhibitory transmission has also been suggested as a mechanism. Because data describing this latter mechanism in...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-199410000-00026

    authors: Hara M,Kai Y,Ikemoto Y

    更新日期:1994-10-01 00:00:00