Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Levorphanol”

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 37 records · Page 2Linked to original sources
PubMed2004

Comparison of the effects of dextromethorphan, dextrorphan, and levorphanol on the hypothalamo-pituitary-adrenal axis.

Dextromethorphan is a weak noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. It is metabolized in vivo to dextrorphan, a more potent noncompetitive NMDA antagonist that is the dextrorotatory enantiomer of the opioid agonist levorphanol. The present study characterized the effects of the acute administration of dextromethorphan, dextrorphan, and levorphanol on the hypothalamo-pituitary-adrenal (HPA) axis in the rat and tested the involvement of opioid receptors in the responses produced by dextrorphan and levorphanol. Although both dextromethorphan and dextrorphan increased plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone, the dextromethorphan-induced responses occurred more rapidly than the dextrorphan-induced responses. The analysis of plasma levels of dextrorphan produced after the administration of dextromethorphan indicates that the concentration of dextrorphan formed was too low to be pharmacologically relevant, suggesting that at least some of the effects on the HPA axis are due to the parent compound, and not the metabolite. Naloxone (2 mg/kg) had no effect on the dextrorphan-induced increases in plasma levels of ACTH and corticosterone, but it blocked the levorphanol-induced increases. These results support the hypothesis that dextromethorphan has pharmacological activity aside from its biotransformation to dextrorphan and demonstrate that the effects of dextrorphan are not mediated by opioid receptors.

Animals↗
PubMed1983

Levorphanol: pharmacokinetics and steady-state plasma concentrations in patients with pain.

Plasma concentrations of the narcotic analgesic, levorphanol, have been determined following i.v., i.m. and oral administration of therapeutic doses of the drug to patients with pain. In two patients who received single i.v. doses of levorphanol the plasma concentration-time profile in each subject was best described by a triexponential decline of the concentrations with terminal half-lives (t 1/2) of about 11 hr. Following i.m. and oral administrations, peak plasma concentrations of intact drug were generally reached after about 0.5 and 1 hr, respectively. Conjugated (beta-glucuronidase labile) levorphanol appeared rapidly in plasma following all routes of administration and quickly reached concentrations which were 5 to 10 fold higher than the intact drug. Effective analgesic steady-state concentrations of levorphanol in patients receiving a wide range of chronic oral and i.m. dosages of the drug ranged from about 10 to 100 ng/ml and these concentrations showed no apparent correlation with either the dose or the subjective analgesic response achieved. The latter observations are probably a reflection of extensive and variable inter-subject "first-pass" metabolism of the drug combined with different degrees of pharmacologic tolerance at the receptor level. However, in the non-tolerant patient it appears that a plasma concentration of about 10 ng/ml is associated with a positive analgesic effect. Furthermore it seems that analgesia is often maintained within a narrow plasma concentration range for each subject in that relatively small decreases in plasma concentration in some patients may be associated with either mild or severe pain. Plasma protein binding at steady-state in 10 patients averaged 40 +/- 2.6%. Concentrations of the drug in the cerebrospinal fluid of 2 patients studied were 60 to 70% of the corresponding plasma levels of the drug.

Humans↗
PubMed1984

Effects of butorphanol, flunixin, levorphanol, morphine, and xylazine in ponies.

The analgesic and behavioral effects of butorphanol (0.22 mg/kg), flunixin (2.2 mg/kg), levorphanol (0.033 mg/kg), morphine (0.66 mg/kg), and xylazine (2.2 mg/kg), given IM were observed in 8 ponies. These ponies were instrumented to measure response objectively to painful superficial and visceral stimuli. Effects on the cardiopulmonary system and rectal temperature also were evaluated in 6 of these ponies. Observations were conducted before drug injection (base-line values) and after injection at 30, 60, 120, 180, and 240 minutes. Xylazine provided the highest pain threshold for the first 60 minutes and a sedative effect for 105 minutes. The effects for superficial pain and visceral pain persisted 3 hours and 4 hours, respectively. Morphine produced good analgesia for superficial pain (30 minutes), whereas butorphanol provided good effect for visceral pain (4 hours). A slight degree of analgesia for visceral pain was obtained after morphine (1 hour) and levorphanol (4 hours); flunixin did not induce analgesia. Butorphanol, levorphanol, and morphine stimulated motor activity. Behavioral effects did not occur after flunixin was given. Xylazine decreased systolic, diastolic, and mean blood pressures. Marked increases in these pressures, heart rate, and respiratory rate were observed after morphine was given. Changes of central venous pressure, rectal temperature, and blood gas values remained within base-line limits after both drugs were given. Butorphanol increased heart rates for 1 hour; flunixin and levorphanol did not alter any of the above values.

Analgesia↗
PubMed1993

Identification with liquid chromatography-ionspray mass spectrometry of the metabolites of the enantiomers N-methyl dextrorphan and N-methyl levorphanol after rat liver perfusion.

To gather more information on stereochemical factors in the hepatic disposition of organic cations, mass spectrometry coupled to liquid chromatography was used to determine the identity of the metabolites excreted in bile after isolated rat liver perfusions with the quaternary ammonium derivatives of the enantiomeric drugs dextrorphan and levorphanol. Ionspray mass spectrometry was chosen for its soft ionization and absence of thermal degradation of labile compounds. The drugs were labelled with a stable (2H) isotope and mixed with unlabelled drugs to create an artificial isotope pattern in the mass spectrum and facilitate the recognition of unknown metabolites. In mass spectra that were recorded under normal conditions, fragmentation was absent and metabolites of N-methyl dextrorphan and N-methyl levorphanol were visible as parent-ion 'doublets'. Collision-induced fragmentation studies were performed to support the identification of the metabolites. For N-methyl dextrorphan the glucuronide, the glutathione conjugate and the glucuronide of the N-demethylated metabolite were found in bile. For N-methyl levorphanol the glucuronide, the glutathione conjugate, the sulphate conjugate and the glucuronide of a hydroxylated N-methyl levorphanol were excreted in bile. Thus a remarkable stereoselectivity occurs in the metabolism of these quaternary ammonium compounds in the rat liver.

Animals↗
PubMed1996

Naloxonazine antagonism of levorphanol-induced antinociception and respiratory depression in rhesus monkeys.

The mu-opioid receptor antagonist effects of naloxonazine on levorphanol-induced thermal antinociception and respiratory depression were examined in rhesus monkeys. Levorphanol (0.032-3.2 mg/kg) produced dose-dependent increases in tail-withdrawal latencies from 50 degrees C water in a warm-water tail-withdrawal assay and dose-dependent decreases in ventilation in both air and 5% CO2 mixed in air. Naloxonazine (0.1-3.0 mg/kg) antagonized both the antinociceptive and ventilatory effects of levorphanol to a similar degree, and the antagonist effects of naloxonazine were greater after 1 h than after 24 h. Under all conditions, the antagonist effects of naloxonazine were fully surmountable. Schild analysis of the antagonist effects of naloxonazine after 1 h pretreatment in the antinociception assay yielded a pA2 value of 7.6 and a slope of -0.50; by comparison, quadazocine yielded a pA2 value of 7.5 and a slope of -1.05. These results suggest that naloxonazine acts as a potent and fully reversible mu-opioid receptor antagonist with a moderately long duration of action in rhesus monkeys. In addition, these results suggest that the antinociceptive and ventilatory effects of mu-opioid receptor agonists in rhesus monkeys are mediated by pharmacologically similar populations of mu opioid receptors.

Analgesia↗
PubMed1982

Cross-tolerance between ethanol and levorphanol with respect to stimulation of plasma corticosterone.

Male rats chronically intoxicated with ethanol for at least two days were tolerant to the ethanol-induced stimulation of hypothalamic-pituitary-adrenal axis. Chronically intoxicated rats also were tolerant to stimulation of this axis by levorphanol but not by amphetamine or ether. In a similar manner, animals treated with levorphanol for two days were tolerant to stimulation of the hypothalamic-pituitary-adrenal axis by either levorphanol or ethanol. These observations provide further support for the hypothesis that endogenous opioids may be involved in the development of tolerance to ethanol.

Alcoholism↗
PubMed1991

Dextromethorphan and levorphanol on dorsal horn nociceptive neurones in the rat.

Intrathecal administration of dextromethorphan and levorphanol and intravenous injection of dextromethorphan were tested on the electrophysiological response of deep multireceptive dorsal horn neurones to peripheral stimuli. Both blockade of C-fibre input to the cells and wind-up, the increase in C-fibre firing with repeated stimulus, were recorded. Intrathecal injection of levorphanol (0.25-100 micrograms) had a typical opioid effect, blocking the C-fibre input. Its affect on wind-up was dose-dependent, paralleled precisely the blocking effect on the C-fibre input and both effects were reversed by naloxone. Unlike levorphanol and other opiates, intrathecal administration of dextromethorphan (50-500 micrograms) blocked the C-fibre input and A beta response in parallel and was not reversed by naloxone. Wind-up was reduced by a maximum of 56% at the largest dose tested. Intravenous injection of dextromethorphan (5 mg/kg) also produced a reduction in wind-up but not in the C-fibre response.

Animals↗
PubMed1970

Tolerance to opioid narcotics, II. Cellular tolerance to levorphanol in mouse brain.

Mice were made tolerant to a large dose of levorphanol, a congener of morphine. Then (3)H-levorphanol was given. The concentration of free, unchanged levorphanol in the brain water (ultrafiltrate) was found to be much higher than required to produce pharmacologic effects in nontolerant animals. The result indicates that tolerance arises from a diminished sensitivity to the drug at cellular or subcellular sites of drug action in the brain.

Animals↗
PubMed1975

Comparative effects of opiate agonists methadone, levorphanol, and their isomers on the release of cortical ACh in vivo and in vitro.

The effect of analgesically active opiate agonists dl-methadone, levorphanol, and their less active forms d-methadone and dextrorphan, respectively, were tested on, (a) the spontaneous release of cortical acetylcholine (ACh) in vivo; (b) the spontaneous and K+-evoked release of cortical ACh in vitro. The injections of dl-methadone, but not d-methadone, inhibited the output of ACh in vivo. Naloxone completely reversed this effect of methadone. Levorphanol in small doses inhibited, and in larger doses stimulated, the in vivo release of ACh. Both effects were antagonized by naloxone. Its dextroisomer dextrorphan was completely inactive. The in vitro release of ACh from cortical slices was inhibited by all four agents. The effects of analgesically active opiates dl-methadone and levorphanol on the in vitro release were not clearly separable from the effects of their inactive forms d-methadone and dextrorphan.

Acetylcholine↗
PubMed1980

Heroin, but not levorphanol, produces explosive motor behavior in naloxone-treated rats.

Intraventricular infusions of heroin (an opiate) or levorphanol (an opioid) in rats produced rigidity but not explosive motor behavior (EMB). When preceded by an IP injection of naloxone, infusions of heroin but not levorphanol produced EMB. The results suggest that naloxone-antagonized effects of opiates mask EMB and that certain opioids do not induce EMB.

Animals↗
PubMed1984

Naloxone blocks the analgesic action of levorphanol but not of dextrorphan in the leopard frog.

Intraspinal injection of levorphanol (3 micrograms) at the lumbar area of the leopard frog, Rana pipiens, induced analgesia which was completely blocked by co-injection of naloxone (3 micrograms), whereas dextrorphan (3 micrograms) induced analgesia which was unaffected by naloxone. Subcutaneous levorphanol (20 or 80 mg/kg) induced a dose-dependent analgesia which was blocked by concurrent naloxone (2 mg/kg), while only the higher dose of dextrorphan (80 mg/kg) induced analgesia which was unaffected by concurrent naloxone at 8 or 80 mg/kg. These data are the first to indicate naloxone-insensitive, dextrorphan-induced analgesia.

Animals↗
PubMed1985

Increased sensitivity to dopamine agonists following a single dose of morphine or levorphanol in mice.

Acute administration of an opiate has been suggested to result in the development of supersensitive dopamine receptors. This hypothesis was tested in mice by determining the effect of a single administration of morphine or levorphanol on dopamine agonist-induced stereotypic behaviors and [3H]spiroperidol binding. Administration of morphine (1.0 mg/kg s.c.), which itself had no significant effect on spontaneous locomotor activity 3 h following administration, significantly potentiated locomotor activity induced by 1.5 or 4.5 mg/kg of apomorphine (i.p.) administered 3 h later. Morphine (10 mg/kg, s.c.) or levorphanol (0.2 and 2.0 mg/kg, s.c.), but not dextrorphan (up to 20 mg/kg, s.c.), enhanced climbing behavior induced by apomorphine (i.p.) or (-)-N-n-propylnorapomorphine (i.p.; NPA) administered 3 h later. An increase in whole brain and striatal [3H]spiroperidol binding sites was found 3 h after administration of 10 mg/kg of morphine. Concurrent administration of 5 mEq/kg of LiCl (i.p.) or 5 mg/kg of naloxone (i.p.; administered twice) attenuated both the potentiation of the climbing behavior induced by the two dopamine agonists and the increase in [3H]spiroperidol binding sites. These results suggest that a single administration of an opiate can induce the development of supersensitive dopamine receptors that is mediated by an interaction at opioid receptors.

Animals↗
PubMed1985

Differential effects of dextrorphan and levorphanol on the excitation of rat spinal neurons by amino acids.

The effects of the stereoisomers dextrorphan and levorphanol on the excitation of spinal neurons by electrophoretically administered excitatory amino acids were studied in pentobarbitone-anaesthetised rats. Both isomers reduced responses to N-methyl-DL-aspartate (NMA), dextrorphan being both more selective and more potent than levorphanol in this respect. This observation supports the proposal that the NMA-blocking activity of a variety of drugs with psychotomimetic properties is subserved by actions at phencyclidine (PCP)/sigma opiate receptors.

Acetylcholine↗
PubMed1986

Preference conditioning produced by opioid active and inactive isomers of levorphanol and morphine in rat.

Using taste and place preference conditioning, the present study examined the motivational properties produced in adult rats by systemic administration of (-) and (+) morphine, levorphanol, and dextrorphan. Conditioned place preference was stereospecific; it was only produced by the opioid receptor active isomers, levorphanol and (-) morphine. Similarly, a conditioned taste preference produced by a low dose of morphine was only seen with the active isomer. Conditioned taste aversion, however, was produced in a comparable dose range by both the active and the inactive isomers. In addition injections of inactive isomers also produced tolerance to the taste aversion produced by (-) morphine. Therefore, administration of both opioid active and inactive isomers of opioid agonists are unconditioned stimuli for the production of preference behaviors. In addition, it was concluded that the appetitive reinforcing properties of these drugs, seen as taste and place preferences, appear to require activation of specific opioid receptors, whereas the aversive effects, seen as taste aversion may also involve other mechanisms.

Animals↗
PubMed1984

Behavioral effects of morphine, levorphanol, dextrorphan and naloxone in the frog Rana pipiens.

Systemic morphine induces explosive motor behavior and generalized muscular rigidity in frogs. Naloxone does not reverse either of these effects of morphine but at high doses causes muscular flaccidity and unresponsiveness to stimulation. Intraspinal morphine induces rigidity, but not explosive motor behavior, and this action is blocked by naloxone. Behavioral effects are seen rarely after intraspinal levorphanol (rigidity) and never after intraspinal dextrorphan or naloxone. In contrast to systemic morphine and naloxone, systemic levorphanol and dextrorphan are lethal to frogs at high doses.

Animals↗
PubMed1999

Quantitation of levorphanol in human plasma at subnanogram per milliliter levels using capillary gas chromatography with electron-capture detection.

A gas chromatographic method for the determination of levorphanol in human plasma is described. The method utilizes extractive alkylation with tetrabutylammonium cation as the phase-transfer catalyst and pentafluorobenzyl bromide as the alkylating agent, and employs a structural analog, d-3-hydroxy-N-ethylmorphinan, as the internal standard. The pentafluorobenzyl ethers formed are separated by capillary gas chromatography and detected by electron capture. The method has good precision and accuracy for concentrations ranging from 0.25 ng/ml to 100 ng/ml and has been used to measure plasma concentrations as part of a study to evaluate the management of chronic neuropathic pain with levorphanol.

Analgesics, Opioid↗
PubMed1971

Stereospecific and nonspecific interactions of the morphine congener levorphanol in subcellular fractions of mouse brain.

A METHOD IS DESCRIBED FOR ANALYZING THE ASSOCIATION OF THE OPIATE NARCOTIC LEVORPHANOL WITH BRAIN TISSUE INTO THREE COMPONENTS: nonsaturable, saturable nonspecific, and saturable stereospecific. The method may be of general applicability for the study of the interaction of drugs with body tissues. In mouse brain the stereospecific binding of levorphanol represents only 2% of the total association of drug with tissue, and it was found only in certain membrane fractions. The material responsible for the stereospecific binding might be the opiate receptor.

Animals↗
PubMed1987

Dextrorphan and levorphanol selectively block N-methyl-D-aspartate receptor-mediated neurotoxicity on cortical neurons.

Neocortical neurons in cell cultures prepared from fetal mice were impaled for intracellular recording. Dextrorphan (DX), a clinically tested dextrorotatory morphinan lacking opioid action, did not alter neuronal membrane potential or conductance, but produced a selective attenuation of N-methyl-D-aspartate (NMDA) responses; kainate and quisqualate responses were not affected. DX also antagonized morphological and chemical (lactate dehydrogenase efflux) evidence of cortical neuronal cell injury produced by toxic bath exposure to NMDA, quinolinate or glutamate, but did not affect toxic exposure to quisqualate or kainate. This selective antagonism of neurotoxicity was apparent at micromolar concentrations of DX with an ED50 of 13 to 17 microM. A similar, but less potent neuron-protective effect, was seen with the opioid levorotatory enantiomer of DX, levorphanol (ED50, 40 microM). The O-methyl derivative of DX, dextromethorphan, also antagonized NMDA and glutamate neurotoxicity, but with possibly lower efficacy than DX. The higher potency of DX over levorphanol suggests that this novel neuron-protective action is not mediated by classic opiate receptors; it may be mediated at the "sigma opiate"/phencyclidine site. If further studies establish that DX and related compounds retain neuron-protective efficacy in appropriate animal models, the established clinical safety record of DX and dextromethorphan may allow prompt investigation of the NMDA receptor-blockade strategy in certain neurological disease states.

Animals↗