Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Butorphanol”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources
PubMed1989

Phosphodiesterase inhibitors potentiate opiate-antagonist discrimination by morphine-dependent rats.

This study was performed to examine the relevance of the quasi-withdrawal syndrome in nondependent rats to the syndrome precipitated by naltrexone in rats physically dependent upon morphine. Morphine-dependent rats trained to discriminate between SC injections of naltrexone (0.1 mg/kg) and saline were pretreated with 10 mg/kg of a phosphodiesterase inhibitor: 3-isobutyl-1-methylxanthine (IBMX), Ro 20-1724, or papaverine. The naltrexone stimulus-generalization curve and dose-response curve for loss of body weight were shifted to the left by IBMX and Ro 20-1724, which produce quasi-withdrawal, but not by papaverine, which does not. IBMX also potentiated the naltrexone-like discriminative effects and loss of body weight induced by cyclazocine, an opioid agonist-antagonist. Butorphanol, another agonist-antagonist, occasioned choice responding appropriate for saline when tested alone but engendered more than 50% naltrexone-appropriate choice responses in rats pretreated with IBMX. Thus, phosphodiesterase inhibitors that produce an opiate quasi-withdrawal syndrome potentiate interoceptive stimuli and weight loss associated with the withdrawal syndrome precipitated by naltrexone in morphine-dependent rats. Furthermore, they appear to enhance the opiate-antagonist activity of opioids with mixed agonist and antagonist properties.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Discriminative stimulus properties of the mixed agonist-antagonist pentazocine in the rat using two-choice discrete-trial avoidance paradigm.

The discriminative stimulus effects of pentazocine were evaluated in the rat trained to discriminate 3.0 mg/kg of pentazocine from vehicle in a two-choice discrete-trial avoidance paradigm. The rats used could discriminate 3.0 mg/kg of pentazocine from vehicle within 20 sessions after the start of discrimination training. The stimulus effects lasted 30 to 90 min and disappeared thereafter except for one rat in which the discriminative effects lasted 30 to 150 min. Pentazocine produced dose-dependent stimulus effects at 0.3 to 3.0 mg/kg doses. The stimulus effects of pentazocine were fully reversed by higher doses of naltrexone. Butorphanol, nalorphine, morphine, levorphanol, SKF 10,047, and methamphetamine generalized to pentazocine cue. However, ethylketocyclazocine, dextrorphan or pentobarbital did not produce stimulus effects in common with pentazocine. These results suggest that the discriminative stimulus effects of pentazocine (3.0 mg/kg) are mediated through an opioid but non-mu and nonspecific mechanism.

Animals↗
PubMed1990

Pharmacological profile of the potentiation of opioid analgesia by restraint stress.

Morphine-treated rats exposed to restraint stress show potentiated magnitude and duration of analgesia compared to unstressed rats. The present study was performed to assess the pharmacological characteristics of stress-induced potentiation of opioid analgesia. We tested 10 opioids to determine whether restraint stress treatment would potentiate their ability to produce antinociception indexed by the tail-flick assay. We tested full mu, delta and kappa opioid receptor agonists (fentanyl, meperidine, DPDPE, U50488H, ethylketocyclazocine), and mixed agonist/antagonists representing a range of receptor selectivities and intrinsic activities (profadol, buprenorphine, pentazocine, butorphanol and nalbuphine). Dose-effect and time-response curves were generated for unrestrained and restrained rats after either subcutaneous (SC) and/or intracerebroventricular (ICV) injections. In restrained rats, all drugs except for SC-administered nalbuphine produced dose- and time-dependent analgesic effects of greater magnitude (1.5-3 times) than they produced in unrestrained rats. However, restrained rats given agonists with high intrinsic activity at the mu receptor displayed the most potent and consistent potentiation of analgesia compared to unrestrained controls. Our results suggest that activation of the mu receptor is of primary importance for restraint to potentiate analgesia, because restrained rats injected with delta and kappa agonists displayed potentiation of analgesia only at doses high enough to possibly exceed the selective activation of their respective receptor types.

Animals↗
PubMed1991

Simple methodology of assessment of analgesics' addictive potential in mice.

Comparative investigation of analgesic (writhing test) and reinforcing (conditioned place preference) effects of 11 opioids over a wide range of doses was performed in mice. On the basis of the dose-response curves analysis, parameters of potency and efficacy of the reinforcing effect were determined. In one group of analgesics (etorphine, fentanyl, buprenorphine, morphine, promedol) ED50 in both tests were approximately equal. The other compounds (pentazocine, nalbuphine, nalorphine, butorphanol, U50,488H) demonstrated dissociation of two effects. The new indices (addictive index and safety index) for the prediction of analgesics' as well as other psychotropic drugs' abuse potential at the preclinical stage of their study have been suggested.

Analgesics, Opioid↗
PubMed1983

A withdrawal hyperalgesia test for physical dependence: evaluation of mu and mixed-partial opioid agonists.

The physical dependence-inducing properties of analgesics are commonly assessed by the appearance of typical narcotic withdrawal signs (weight loss, jumping, etc.) upon cessation of administration or treatment with a narcotic antagonist. We sought to develop a simple model of physical dependence based upon withdrawal hyperalgesia. The test compound was injected seven times over a period of three days. At various times after the last injection, 6% aqueous NaCl was injected i.p. and the mice were observed for stereotyped writhing. To assess the magnitude of hyperalgesia, the animals were also challenged with several concentrations of saline administered at the time of peak sensitivity and a saline EC50 was thereby derived. In this manner, it was demonstrated that morphine causes a marked, dose-related physical dependence. Other mixed opioids, pentazocine, ethylketocyclazocine, nalbuphine, and butorphanol (in decreasing order of effectiveness) were also active. In nonpretreated mice, naloxone caused a dose-related appearance of saline-induced writhing, suggestive of a blockade of endogenous analgesic mechanisms. Writhing in response to low concentrations of i.p. saline provides a sensitive test of analgesic physical dependence.

Analgesics, Opioid↗
PubMed1995

Opioid peptide receptor studies. 3. Interaction of opioid peptides and other drugs with four subtypes of the kappa 2 receptor in guinea pig brain.

Using guinea pig, rat, and human brain membranes depleted of mu and delta receptors by pretreatment with the site-directed acylating agents BIT (mu selective) and FIT (delta selective), previous studies from our laboratory resolved two subtypes of the kappa 2 binding site, termed kappa 2a and kappa 2b. In more recent studies, we used 6 beta-[125Iodo]-3,14-dihydroxy-17-cyclopropylmethyl-4,5 alpha-epoxymorphinan ([125I]IOXY) to characterize multiple kappa 2 binding sites in rat brain. The results indicated that [125I]IOXY, like [3H]bremazocine, selectively labels kappa 2 binding sites in rat brain membranes pretreated with BIT and FIT. In the rat brain, using 100 nM [D-Ala2-MePhe4,Gly-ol5]enkephalin to block [125I]IOXY binding to the kappa 2b site, we resolved two subtypes of the kappa 2a binding site. In the present study we examined the binding of [125I]IOXY to the kappa 2 receptors of guinea pig brain. As observed in rat brain, [125I]IOXY, under appropriate assay conditions, selectively labels kappa 2 binding sites. Quantitative binding studies readily demonstrated the presence of kappa 2a and kappa 2b binding sites. The kappa 2a binding sites were selectively assayed using 5 microM [Leu5]enkephalin to block [125I]IOXY binding to the kappa 2b sites, and kappa 2b sites were selectively assayed using 5 microM (-)-(1S,2S)-U50,488 to block [125I]IOXY binding to the kappa 2a sites. Under these conditions, two subtypes of the kappa 2a site were resolved with high (kappa 2a-1) and low (kappa 2a-2) affinity for nor-BNI (Ki values = 0.88 and 476 nM) and CI977 (Ki values = 17.5 and 95,098 nM). Similarly, two subtypes of the kappa 2b site were observed with high (kappa 2b-1) and low (kappa 2b-2) affinity for [D-Ala2-MePhe4,Gly-ol5]enkephalin (DAMGO) (Ki values = 97 and 12,321 nM) and alpha-neoendorphin (Ki values = 33 and 5308 nM). Two-site models were also resolved in the presence of 100 microM 5'-guanylyimidodiphosphate (GppNHp). We carried out detailed ligand selectivity analysis of the multiple kappa 2 binding sites. Most test agents were either nonselective or selective for the kappa 2a-1 site. Nalbuphine was moderately selective for the kappa 2a-2 site. Similarly, although most test agents were either nonselective or selective for the kappa 2b-1 site, butorphanol, and the delta antagonists naltrindole, naltriben, and 7-benzylidene-7-dehydronaltrexone were moderately selective for the kappa 2b-2 site.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1985

Historical introduction and review of chemistry.

A historical introduction and review of the chemistry of the agonist-antagonist analgesics is presented. This development of strong analgesics with a lowered abuse potential from nalorphine to the clinically useful agonist-antagonists pentazocine, butorphanol, nalbuphine and buprenorphine is discussed in detail. The discovery of the pure antagonist naloxone and naltrexone is described. The possible use of cyclazocine and later naltrexone in treatment of post-dependent narcotic addicts is also described. Finally, structure-activity relationships are summarized relating changes in N-alkylation to the production of narcotic antagonist activity over all of the structural types of opioids.

Analgesics↗
PubMed1985

Nalbuphine.

Nalbuphine is a potent analgesic with a low side effect and dependence profile in animals and man. Nalbuphine is distinguished from other agonist/antagonist analgesics in having greater antagonist activity and fewer behavioral effects at analgesic doses than pentazocine, butorphanol or buprenorphine. At equi-analgesic doses, nalbuphine is quantitatively similar to nalorphine in regard to its large ratio of antagonist to analgetic activity. Clinical studies have confirmed this balance of strong antagonist to analgesic activity. Nalbuphine has been shown to effectively antagonize the respiratory depressant activity of narcotic analgesics while concomitantly adding to their analgetic responses. Unlike nalorphine or pentazocine, nalbuphine produces few overt behavioral or autonomic effects in animals at doses over 300 times its analgesic range. These findings are confirmed by clinical results which show that nalbuphine produces few psychotomimetic effects, even at elevated dose levels, in contrast to nalorphine or pentazocine. Nalbuphine produces limited respiratory depression in animals and in man. Significant cardiovascular effects have not been found. Nalbuphine was found to produce significantly less inhibition of gastrointestinal activity than any of the clinically useful narcotic or agonist/antagonist analgesics tested in animals. Nalbuphine's analgetic effects are reversed by naloxone doses similar to those which reverse nalorphine's agonist effects. Results in this and other tests suggest that nalbuphine is primarily a kappa-agonist/mu-antagonist analgesic. Unlike pentazocine or buprenorphine, nalbuphine does not suppress the narcotic abstinence syndrome in partly-withdrawn morphine-dependent animals or man. Rather, due to nalbuphine's strong antagonist activity, analgesic-range doses of nalbuphine severely exacerbate the withdrawal syndrome in partly-withdrawn mice, monkeys and humans. Nalbuphine also precipitates a strong abstinence response in non-withdrawn morphine-dependent animals and man. In post-addict humans, analgesic-range doses of nalbuphine are perceived as minimally morphine-like, but higher doses are judged to be progressively more nalorphine-like (i.e. dysphoric), which further limits nalbuphine's abuse potential in drug-seeking individuals. Primary dependence studies have demonstrated that physical dependence is possible at high dose levels that produce marked side effects. Other studies show that dependence is unlikely to be of significance within nalbuphine's usual analgesic range. Six-month studies in patients with chronic pain have confirmed that analgesic tolerance or physical dependence is uncommon.(ABSTRACT TRUNCATED AT 400 WORDS)

Analgesics↗
PubMed1987

The clinical usefulness of agonist-antagonist analgesics in acute pain.

The opioid agonist-antagonists are a heterogeneous group of compounds capable of providing analgesia sufficient to treat moderate to severe acute pain. Pentazocine, butorphanol and nalbuphine produce subjective effects which are quite different from those of morphine. Lack of mood elevation and occasional dysphoria may contribute to a lower level of patient acceptance, but all of these analgesics are significantly safer than the pure agonists. Doses in the therapeutic range are unlikely to produce dangerous levels of respiratory depression in most patients. Other opioid side-effects such as nausea, constipation and biliary spasm appear to be less frequent as well. The mu partial agonist buprenorphine shares many of the safety advantages of the older drugs, and its subjective effects appear more morphine-like. It is not clear whether mu partial agonists have real clinical advantages over kappa-type analgesics. All of these drugs are opioid antagonists and are able to precipitate abstinence in individuals with significant prior exposure to opiates. Neither absolute potency nor the ratio of agonist to antagonist effect are predictors of therapeutic usefulness. There is now an enormous amount of clinical experience with the agonist-antagonists. In many, but not all, clinical situations they are acceptable alternatives to the morphine-like drugs.

Analgesics, Opioid↗
PubMed1987

The clinical usefulness of agonist-antagonistic opioid analgesics in chronic pain.

The mixed agonist-antagonist analgesics do not have a major role in the treatment of chronic pain. Pentazocine, the first and most widely used of this group of drugs has two major limitations: by mouth it is not a strong analgesic, but is closer in efficacy to the peripherally acting drugs aspirin and paracetamol than the weak opioids; and its use is associated with psychotomimetic side effects in 10-20 percent of patients. The weak opioid analgesics codeine and dextropropoxyphene are more effective and better tolerated than pentazocine. Buprenorphine is the most useful of the agonist-antagonists in chronic pain patients. It is potent, long-acting (6-9 h) and effective when given sublingually. However, it has a limited effective dose range and produces the same side effects as morphine-like drugs, possibly more frequently at equianalgesic doses. It may be used in the treatment of cancer pain, or in patients with chronic arthritides or other forms of chronic non-cancer pain who require a potent conventional analgesic, as an alternative to the weak opioids or to morphine in low doses. Nalbuphine and butorphanol are only available for parenteral administration which means that their usefulness in the treatment of chronic pain is limited. Meptazinol is restricted by its manufacturers to 'short term' treatment and there is little information on its use in chronic pain patients.

Analgesics, Opioid↗
PubMed1991

Abuse liability studies of opioid agonist-antagonists in humans.

Prediction of the abuse liability of a drug before it reaches the market is complicated by the fact that there are many factors that influence the actual abuse of a drug. Laboratory methods used in humans to assess the abuse liability of the opioids are reviewed and illustrative studies of morphine and the agonist-antagonist opioids, pentazocine, butorphanol, nalbuphine and buprenorphine, are presented. Three assessment methods, subjective effect measurement, self-administration and drug discrimination, provide information relevant to measuring reinforcing efficacy, a major determinant of the degree to which a drug is sought and self-administered by abusers. Physical dependence capacity, which can contribute to sustained drug use, is evaluated in direct addiction and substitution/suppression studies. Withdrawal precipitation studies measure antagonist activity which might limit abuse. The results of testing the agonist-antagonist opioids are generally consistent across these various methods and consistent with historical experience with these drugs, suggesting that these methods are useful in predicting abuse liability of novel opioids.

Arousal↗
PubMedDate not supplied

Anesthetic management of a patient with Bartter's syndrome.

Bartter's syndrome is a rare disorder characterized by normal or low arterial blood pressure (BP), despite marked elevation in plasma renin activity, angiotensin II (Ang-II), and aldosterone, along with hypokalemic metabolic alkalosis. Perioperative changes in the cardiovascular and renin-angiotensin-aldosterone (RAA) systems in Bartter's syndrome patients are not well understood. We managed a 44-year-old Japanese man with rectal cancer and Bartter's syndrome complicated by renal dysfunction. He underwent anterior resection of the rectum with general anesthesia (50% nitrous oxide-oxygen with 0.5% to 0.8% isoflurane, supplemented with intravenous midazolam and butorphanol). Epidural morphine was given postoperatively. Although BP tended to be lower (75/35 to 110/60 mmHg) during surgery, there were no profound perioperative hemodynamic derangements. Plasma renin activity. Ang-II, and aldosterone values were highest during surgery. These responses of the RAA system to anesthesia and surgery were the same as previously noted in otherwise healthy surgical patients.

Adult↗
PubMed2006

Comparison of the in vitro efficacy of mu, delta, kappa and ORL1 receptor agonists and non-selective opioid agonists in dog brain membranes.

Morphine and related opioid agonists are frequently used in dogs for their analgesic properties, their sedative effects and as adjuncts to anesthesia. Such compounds may be effective through a combined action at mu-, delta- and kappa-opioid receptors. In this work, the in vitro relative agonist efficacy of ligands selective for mu (DAMGO)-, delta (SNC80)- and kappa (U69593)-opioid receptors as well as the opioid receptor-like receptor ORL(1) (orphaninFQ/nociceptin) which may mediate nociceptive or antinociceptive actions was determined using the [35S]GTPgammaS binding assay in membrane homogenates from the frontal cortex, thalamus and spinal cord of beagle dogs. In addition, other analgesics commonly used in the dog were investigated. For the receptor-selective compounds, maximum stimulation of [35S]GTPgammaS binding decreased in the order kappa > ORL1 > delta > mu in cortical homogenates, compared with mu > ORL1 > kappa > delta in thalamic and spinal cord homogenates. For other opioids examined, efficacy decreased in the order etorphine >> morphine > fentanyl = oxymorphine > butorphanol = oxycodone = nalbuphine. There was no significant difference in the potency of compounds to stimulate [35S]GTPgammaS binding between cortex and thalamus, with the exception of etorphine. Buprenorphine, the partial mu-opioid receptor agonist and kappa-, delta-opioid receptor antagonist, which does have analgesic efficacy in the dog, showed no agonism in any tissue but was an effective mu-opioid receptor > ORL1 receptor antagonist. The results show that the ability of agonists to stimulate [35S]GTPgammaS binding relates to the receptor distribution of opioid and ORL1 receptors in the dog.

Analysis of Variance↗
PubMed2004

Postoperative management of the large colon volvulus patient.

Horses with large colon volvulus (LCV) often require intensive postoperative medical management. Although early referral and surgical intervention are critical for minimal postoperative complications and a successful outcome, this is often not possible for many reasons. Endotoxemia, extensive mucosal damage with subsequent severe hypoproteinemia, and focal ischemic necrosis are the major causes of postoperative morbidity and mortality. Although fluid therapy, flunixin meglumine, and antimicrobials are still the mainstay of perioperative management, synthetic colloids are being used to maintain plasma oncotic pressure, hyperimmune antiendotoxic plasma and polymixin B are being used for management of endotoxemia, and lidocaine and constant rate infusion of butorphanol can be used for postoperative analgesia. The use of heparin, dimethyl sulfoxide, and corticosteroids for management of LCV are still controversial. Future studies are required to investigate nutritional improvement and methods to manage cases after surgery to prevent recurrence.

Animals↗
PubMed2004

Pain management in cats--past, present and future. Part 2. Treatment of pain--clinical pharmacology.

Opioids have an unjustified reputation for causing mania in cats, but with refinements in dosing they are now used successfully in this species. The mu-opioid agonists are generally considered the best analgesics. Morphine (0.1-0.3 mg/kg) is effective in a clinical setting. Methadone (up to 0.5 mg/kg) has a similar profile to morphine. Pethidine (Demerol, meperidine; 2-5 mg/kg) is a useful analgesic with a faster onset but shorter duration of action than morphine. Oxymorphone and hydromorphone (0.05-0.1 mg/kg) are widely used in the USA. These opioids are more potent (up to 10 times), and longer acting than morphine in cats. Butorphanol (0.1-0.4 mg/kg) is a mu-opioid antagonist that produces its analgesic actions through kappa agonist activity. It rapidly reaches a ceiling effect, is short acting and is a weaker analgesic than pure mu opioids. Buprenorphine (0.01-0.02 mg/kg), a partial mu-agonist, is the most popular opioid used in small animal practice in the UK, other parts of Europe, Australia and South Africa. In clinical studies it has produced better analgesia than several other opioids and appears to be highly suitable for perioperative pain management in cats. NSAIDs are also used in cats for pain management, although cats metabolise these differently from other species. With appropriate dosing, carprofen (1-4 mg/kg) and meloxicam (0.3 mg/kg) have proved highly effective with few side effects. The use of ketoprofen (2 mg/kg), tolfenamic acid (4 mg/kg) and vedaprofen (0.5 mg/kg) has been reported in cats. Other less traditional analgesics such as ketamine, medetomidine and local anaesthetics are also used for clinical pain management. The transmucosal, transdermal and epidural routes offer novel methods for administration of analgesic drugs and have considerable potential for improving techniques in feline pain management.

Analgesics↗
PubMed2002

Sex-related differences in mechanical nociception and antinociception produced by mu- and kappa-opioid receptor agonists in rats.

Previous studies indicate that in antinociceptive procedures employing thermal, chemical and electrical stimuli, opioids are generally more potent in male than female rodents. The purpose of the present study was to examine nociception and opioid antinociception in male and female rats using a mechanical nociceptive stimulus. Results indicated that males had a higher threshold for nociception, and in tests in which a constant pressure was applied to the hindpaw, the paw withdrawal latencies were consistently longer in males. Opioids with activity at the mu receptor, including levorphanol, morphine, dezocine, buprenorphine, butorphanol and nalbuphine, were generally more potent and/or effective in males. In contrast, sex differences were not consistently observed with the kappa-opioid receptor agonists spiradoline, (5,7,8b)-N-methyl-N[2-1(1-pyrrolidinyl),1-oxaspiro[4,5]dec-8-yl benzeneacetamide (U69593), trans-(+/-)-3,4-dichloro-N-methyl-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide (U50488), enadoline, ethylketocyclazocine, and nalorphine. These findings suggest that males and females differ in their responsiveness to mechanical nociception and that sex differences in sensitivity to kappa-, but not mu-, opioid receptor agonists are specific to certain nociceptive stimulus modalities.

Analgesics↗
PubMed1998

Determination of sedatives and anesthetics in plasma by liquid chromatography-mass spectrometry with a desalting system.

Though liquid chromatography-mass spectrometry (LC-MS) is a powerful tool for analysis of drugs and their metabolites, it does not allow the use of a non-volatile buffer such as phosphate buffer. We used a column-switching desalting system in combination with atmospheric pressure chemical ionization LC-MS for analysis of sedatives and anaesthetics. The drugs examined were flumazenil, butorphanol, midazolam, lorazepam, phenobarbital and flunitrazepam. The separation was carried out on a reversed-phase column using acetonitrile-0.1 M phosphate buffer as a mobile phase. The mass spectra are almost the same as those obtained by direct analysis and the molecular ions were clearly observed. In the analysis, phosphate buffer was completely removed with the trapping column and did not interfere with ionization of the drugs in MS. The chiral separation of lorazepam was achieved on a chiral column with UV, optical rotatory detection and MS. This method is sufficiently sensitive and accurate for the pharmacokinetic studies of these drugs in biological samples.

Anesthetics↗
PubMed2004

Catastrophic thinking about pain increases discomfort during internal atrial cardioversion.

OBJECTIVES: This study investigated whether pain catastrophizing is associated with distress and perceived disability in patients with atrial fibrillation, whether pain catastrophizing predicts pain and fear during a medical procedure of atrial cardioversion, and whether pain catastrophizing influences the effects of an opioid analgesic during internal cardioversion. METHODS: A secondary analysis is performed upon data from a double-blind placebo-controlled trial during which the effect of intranasal butorphanol tartrate (INB) was evaluated in patients with atrial fibrillation using a step-up internal atrial cardioversion protocol. Before the procedure, patients completed measures of pain catastrophizing, mood, distress and perceived disability. After each shock, patients completed measures of pain and fear. RESULTS: We found that pain catastrophizing predicted the affective pain rating of the first shock, and the fear increase during subsequent shocks. There was no effect of INB. However, when controlling for the differences in pain catastrophizing, INB significantly reduced fear as compared to placebo. This suggests that the effects of INB during atrial cardioversion were overshadowed by the effects of pain catastrophizing. CONCLUSIONS: It is recommended that in future atrial cardioversion trials, stratification based on pain catastrophizing be performed. Reducing catastrophizing thinking about pain through cognitive-behavioral techniques are likely to reduce levels of fear during internal atrial cardioversion and may increase the effectiveness of concomitant analgesics.

Adult↗