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PubMed2002

Butorphanol dependence and withdrawal decrease hippocampal kappa 2-opioid receptor binding.

The present study examines the degree and distribution of alterations in the expression of kappa-opioid receptor subtypes using a model of chronic intracerebroventricular (i.c.v.) infusion of butorphanol. Autoradiographic characterization of binding for brain kappa(1) ([3H]CI-977)-, kappa(2) ([3H]bremazocine in the presence of DAMGO, DPDPE, and U-69,593)- and total kappa ([3H]bremazocine in the presence of only DAMGO and DPDPE)-opioid receptors was performed. Dependence was induced by a 72 h i.c.v. infusion with butorphanol (26 nmol/microl per hour) (butorphanol-dependent). Butorphanol withdrawal was produced by terminating the infusion of butorphanol in dependent animals. Responses were studied 7 h following termination (butorphanol-withdrawal). During both dependence and withdrawal phases, the binding signals for both kappa(1)- and kappa(2)-opioid receptors were significantly increased in certain regions, with especially marked increases in the frontal cortex, nucleus accumbens, parietal cortex, dorsomedial hypothalamus, ventral tegmental area and locus coeruleus. In contrast, a highly specific decrease in kappa(2)-, but increase in kappa(1)-, opioid receptor binding was noted in the hippocampus of rats in both butorphanol-dependent and-withdrawal groups. Therefore, alterations in kappa(1)- and kappa(2)-opioid receptors in the hippocampus may be differently involved in both adaptation to and recovery from chronic exposure to a mixed agonist/antagonist opioid analgesic. These results further illustrate the regional distribution of changes in binding characteristics of rat brain kappa(1)- and kappa(2)-opioid receptor subtypes in an established model of butorphanol dependence and withdrawal.

Animals↗

PubMed2003

Possible mechanism involved in the anticonvulsant action of butorphanol in mice.

The study was designed to examine the effect of butorphanol, a classical opioid on convulsive behaviour using maximal electroshock (MES) test. An attempt was also made to investigate the role of possible receptor mechanisms involved. MES seizures were induced in mice via transauricular electrodes (60 mA, 0.2 s). Seizure severity was assessed by the duration of tonic hindlimb extensor phase and mortality due to convulsions. Intraperitoneal administration of butorphanol produced a dose-dependent (0.25-2 mg/kg) protection against hindlimb extensor phase. The anticonvulsant effect of butorphanol was antagonized by all the three opioid receptor antagonists (i.e., naloxone [mu], MR2266 [kappa], and naltrindole [delta], respectively). Coadministration of gamma-aminobutyric acid (GABA)-ergic drugs (diazepam, GABA, muscimol, and baclofen) and N-methyl-D-aspartate (NMDA) receptor antagonist, dizocilpine (MK801), with butorphanol augmented the anticonvulsant action of the latter drug. In contrast, flumazenil, a central benzodiazepine (BZD) receptor antagonist, reversed the facilitatory effect of diazepam on the anti-MES effect of butorphanol. Similarly, delta-aminovaleric acid (DAVA), a GABA(B) receptor antagonist, antagonized the facilitatory effect of baclofen, a GABA(B) agonist on anti-MES action of butorphanol. These BZD-GABAergic antagonists, flumazenil or DAVA, per se also counteracted the anti-MES effect of butorphanol given alone. These data exemplify the benefits of using the MES test, which is sensitive to opioidergic compounds and distinguished convulsive behavioural changes associated with GABAergic and NMDAergic effects. Taken together, the results implicate a role for multitude of neurotransmitter systems, i.e., opioid (mu, kappa, delta), NMDA channel, BZD-GABA(A) chloride channel complex, and GABA(B) receptors in the anti-MES action of butorphanol.

Analgesics, Opioid↗

PubMed1998

Relative involvement of spinal opioid receptors in physical dependence on intrathecal butorphanol and morphine.

The present study was carried out to investigate the relative involvement of spinal opioid receptors in the development of physical dependence on intrathecal (i.t.) butorphanol in comparison with i.t. morphine. Dependence was induced by continuous i.t. infusion of butorphanol (52 nmol/h) and morphine (26 nmol/h) for 4 days in male Sprague-Dawley rats. Naloxone, CTOP, naltrindole, and nor-binaltorphimine (nor-BNI) were administered i.t. to precipitate behavioral signs of withdrawal. Administration of i.t. naloxone produced a significantly greater increase in the profile of withdrawal signs in i.t. morphine dependence than that in i.t. butorphanol dependence. An i.t. nor-BNI challenge elicits behavioral signs of withdrawal only in rats dependent on i.t. butorphanol, but not in rats dependent on i.t. morphine. CTOP administered i.t. precipitated withdrawal signs in i.t. morphine dependence that were greater than that in i.t. butorphanol dependence. An i.t. treatment with naltrindole produced equivalent signs of withdrawal in both i.t. butorphanol- and morphine-dependent rats. These results suggest that continuous i.t. butorphanol results in the development of less physical dependence than that of i.t. morphine. Spinal kappa- rather than delta- and mu-opioid receptors play a major role in the development of i.t. butorphanol dependence, whereas spinal mu-opioid receptors play a more important role than delta-opioid receptors in i.t. morphine dependence.

Animals↗

PubMed2003

Changes in the brain kappa-opioid receptor levels of rats in withdrawal from physical dependence upon butorphanol.

Changes in kappa-opioid receptor levels have been implicated in the development of physical dependence upon and withdrawal from the mixed agonist-antagonist opioid, butorphanol. Immunoblotting analysis was performed to determine the levels of kappa- and mu-opioid receptors in brain regions of rats in withdrawal from dependence upon butorphanol or morphine. Physical dependence was induced by a 72 h i.c.v. infusion with either butorphanol or morphine (26 nmol/microl/h). Withdrawal was subsequently precipitated by i.c.v. challenge with naloxone (48 nmol/5 microl/rat), administered 2 h following cessation of butorphanol or morphine infusion. Immunoblotting analysis of kappa-opioid receptors from butorphanol-withdrawal rats showed significant increases in 11 of 21 brain regions examined, including the nucleus accumbens, amygdala, dorsomedial hypothalamus, hypothalamus, paraventricular thalamus, thalamus, presubiculum, and locus coeruleus, when compared with saline treated, non-dependent controls. In addition, significant reductions were found in the hippocampus and in cortical brain regions, including the parietal cortex and temporal cortex from butorphanol-withdrawal rats. These findings contrasted with those from morphine-withdrawal rats, in which the only changes noted were increases in the thalamus and paraventricular thalamus. Changes in the levels of the mu-opioid receptor protein were observed in 11 of 21 brain regions examined in morphine-withdrawal rats, but only in three of 21 in butorphanol-withdrawal rats. These results implicate a substantive and largely unique role for kappa-opioid receptors in mediation of the development of physical dependence upon, and the expression of withdrawal from, butorphanol, as opposed to the prototypical opioid analgesic, morphine.

Animals↗

PubMed2000

Modulation of NMDA receptor subunit mRNA in butorphanol-tolerant and -withdrawing rats.

The NMDA receptor has been implicated in opioid tolerance and withdrawal. The effects of continuous infusion of butorphanol on the modulation of NMDA receptor subunit NR1, NR2A, NR2B, and NR2C gene expression were investigated by using in situ hybridization technique. Continuous intracerebroventricular (i.c.v.) infusion with butorphanol (26 nmol/microl/h) resulted in significant modulations in the NRI, NR2A, and NR2B mRNA levels. The level of NR1 mRNA was significantly decreased in the cerebral cortex, thalamus, and CA1 area of hippocampus in butorphanol tolerant and withdrawal (7 h after stopping the infusion) rats. The NR2A mRNA was significantly decreased in the CA1 and CA3 of hippocampus in tolerant rats and increased in the cerebral cortex and dentate gyrus in butorphanol withdrawal rats. NR2B subunit mRNA was decreased in the cerebral cortex, caudate putamen, thalamus, CA3 of hippocampus in butorphanol withdrawal rats. No changes of NR1, NR2A, NR2C subunit mRNA in the cerebellar granule cell layer were observed in either butorphanol tolerant or withdrawal rats. Using quantitative ligand autoradiography, the binding of NMDA receptor ligand [3H]MK-801 was increased significantly in all brain regions except in the thalamus and hippocampus, at the 7 hr after stopping the butorphanol infusion. These results suggest that region-specific changes of NMDA receptor subunit mRNA (NR1 and NR2) as well as NMDA receptor binding ([3H]MK-801) are involved in the development of tolerance to and withdrawal from butorphanol.

Animals↗

PubMed1993

Multiple-dose phase I study of transnasal butorphanol.

The safety, tolerance, and pharmacokinetics of transnasal butorphanol were evaluated in a double-blind, multiple-dose phase I study. A total of 18 subjects received either placebo (n = 6) or a single transnasal dose of 2 mg butorphanol tartrate on the first day and 1, 2, and 4 mg doses of butorphanol tartrate every 6 hours on days 2 through 6, 7 through 11, and 12 through 16, respectively. Safety assessment was performed on days 7, 12, and 17. Serial blood samples were collected on days 1, 6, 11, and 16, and the plasma was analyzed for unchanged butorphanol by a validated and specific radioimmunoassay. Butorphanol was rapidly absorbed and peak levels in plasma were generally attained within 1 hour after the nasal administration. The values of maximum concentration, minimum concentration, and area under the concentration versus time curve from time zero to the dosing interval [AUC(0-tau)] increased as the administered dose increased in a dose-proportional manner. The values of AUC from time zero to infinity after a single dose of 2 mg butorphanol tartrate, 10.9 ng.hr/ml, were identical to the values of AUC(0-tau) after a multiple administration of 2 mg dose, 10.4 ng.hr/ml. Mean elimination half-life value was 5.45 hours. Steady state was reached in fewer than eight doses when given every 6 hours. Transnasal butorphanol was well tolerated by all subjects. After repeated administration of transnasal butorphanol, no significant changes were observed in the nasal examination, which included evaluation of color, wetness, and thickness of nostril membrane, air flow, airway patency, and general nasal conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

PubMed2005

Comparison of morphine and butorphanol as pre-anaesthetic agents in combination with romifidine for field castration in ponies.

OBJECTIVE: The aim of this study was to compare two different alpha2 agonist-opioid combinations in ponies undergoing field castration. STUDY DESIGN: Prospective double-blind randomized clinical trial. ANIMAL POPULATION: Fifty-four ponies undergoing field castration. MATERIALS AND METHODS: The ponies were randomly allocated to receive one of three different pre-anaesthetic medications [intravenous (IV) romifidine 100 microg kg(-1) and butorphanol 50 micro kg(-1); romifidine 100 microg kg(-1) and morphine 0.1 mg kg(-1) IV, or romifidine 100 microg kg(-1) and saline IV] before induction of anaesthesia with ketamine 2.2 mg kg(-1) IV. Further doses of romifidine (25 microg kg(-1)) and ketamine (0.5 mg kg(-1)) were given when required to maintain anaesthesia. Quality of sedation, induction of anaesthesia, maintenance of anaesthesia, recovery, and surgical condition were assessed using a visual analogue scale scoring system and compared. The effects of the different drug combinations on heart and respiratory rate were evaluated and the recovery time was recorded. RESULTS: Anaesthesia was considered adequate for surgery in all ponies. No anaesthetic complications were observed. Quality of sedation was significantly better in the butorphanol group compared with the control group (p = 0.0428). Overall quality of anaesthesia was better in the butorphanol group compared with morphine (p = 0.0157) and control (p < 0.05) groups. Quality of induction of anaesthesia and recovery were not significantly different between groups, nor were the surgical conditions, recovery time and the number of repeated anaesthetic doses required during the procedure. Muscle twitches were observed in both the control and morphine groups. Maintenance of anaesthesia was judged to be smoother in the butorphanol group compared with the morphine and control groups (p = 0.006). Heart rate decreased significantly (p < 0.01) in all groups after administration of sedatives but did not differ significantly between groups at any time point. CONCLUSION: The combination of butorphanol and romifidine was found to provide better sedation compared with the other drug combinations. CLINICAL RELEVANCE: The combination of butorphanol and romifidine provided better sedation, but morphine was found to be a suitable alternative to butorphanol. Use of morphine and butorphanol in combination with alpha2 agonists should be further investigated to assess their analgesic effects.

Analgesics, Opioid↗

PubMed2001

Pharmacokinetics and pharmacodynamics of butorphanol in llamas after intravenous and intramuscular administration.

OBJECTIVE: To evaluate disposition of butorphanol after i.v. and i.m. administration, effects on physiologic variables, and analgesic efficacy after i.m. administration in llamas. DESIGN: Nonrandomized crossover study. ANIMALS: 6 healthy adult male llamas. PROCEDURE: Butorphanol (0.1 mg/kg [0.045 mg/lb] of body weight) was administered i.m. first and i.v. 1 month later. Blood samples were collected intermittently for 24 hours after administration. Plasma butorphanol versus time curves were subjected to pharmacokinetic analysis. Two months later, butorphanol (0.1 mg/kg) was administered i.m., and physiologic variables and analgesia were assessed. RESULTS: Extrapolated peak plasma concentrations after i.v. and i.m. administration were 94.8 +/- 53.1 and 34.3 +/- 11.6 ng/ml, respectively. Volume of distribution at steady state after i.v. administration was 0.822 +/- 0.329 L/kg per minute and systemic clearance was 0.050 +/- 0.014 L/kg per minute. Slope of the elimination phase was significantly different, and elimination half-life was significantly shorter after i.v. (15.9 +/- 9.1 minutes) versus i.m. (66.8 +/- 13.5 minutes) administration. Bioavailability was 110 +/- 49% after i.m. administration. Heart rate decreased and rectal temperature increased. Somatic analgesia was increased for various periods. Two llamas became transiently sedated, and 2 became transiently excited after butorphanol administration. CONCLUSIONS AND CLINICAL RELEVANCE: Although i.v. administration of butorphanol results in a short half-life that may limit its analgesic usefulness, the elimination half-life of butorphanol administered i.m. is likely to be clinically useful. The relationship among plasma butorphanol concentration, time, and analgesia differed with the somatic analgesia model; clinically useful analgesia may occur at lower plasma concentrations than those reported here.

Analgesics, Opioid↗

PubMedDate not supplied

Comparison of anesthetic and cardiorespiratory effects of tiletamine-zolazepam-xylazine and tiletamine-zolazepam-xylazine-butorphanol in ferrets.

Nine ferrests were used in a crossover study to determine the anesthetic effects of intramuscular (i.m.) administration of a low dose of tiletamine-zolazepam (1.5 mg/kg body weight)-xylazine (1.5 mg/kg body weight); a high dose of tiletamine-zolazepam (3 mg/kg body weight)-xylazine (3 mg/kg body weight); and tiletamine-zolazepam (1.5 mg/kg body weight)-xylazine (1.5 mg/kg body weight)-butorphanol (0.2 mg/kg body weight). All ferrets became laterally recumbent within two minutes following the administration of each drug combination. The tiletamine-zolazepam-xylazine-butorphanol combination induced significantly longer (p less than 0.05) durations of tail clamp analgesia (mean +/- standard deviation [SD], 90.0 +/- 17.1 min versus 17.8 +/- 15.8 min and 41.9 +/- 26.3 min) and endotracheal intubation (mean +/- SD, 84.8 +/- 21.7 min versus 5.2 +/- 10.3 min and 26.3 +/- 29.8 min) than the low-dose tiletamine-zolazepam-xylazine and high-dose tiletamine-zolazepam-xylazine combinations, respectively. Heart rates and the times from dorsal recumbency to standing were not significantly different among the three treatment groups. However, systolic blood pressure was significantly lower in the tiletamine-zolazepam-xylazine-butorphanol group. Ventilatory function was more depressed in the tiletamine-zolazepam-xylazine-butorphanol group than in the low-dose tiletamine-zolazepam-xylazine and high-dose tiletamine-zolazepam-xylazine groups. A short period of hypoxia was observed in the tiletamine-zolazepam-xylazine-butorphanol-treated ferrets. Tiletamine-zolazepam-xylazine-butorphanol was found to be the best of the three combinations evaluated in these ferrets. The addition of butorphanol to the low-dose tiletamine-zolazepam-xylazine combination greatly enhanced the duration of analgesia, endotracheal intubation, and dorsal recumbency. However, since hypoxemia occurred during the tiletamine-zolazepam-xylazine-butorphanol anesthesia, oxygen (O2) insufflation is recommended. Doubling the dose of the low-dose tiletamine-zolazepam-xylazine increased the duration of analgesia and endotracheal intubation without prolonging the recovery when compared to the low-dose tiletamine-zolazepam-xylazine group.

Analgesics, Opioid↗

PubMed1987

Epidural butorphanol or morphine for the relief of post-cesarean section pain: ventilatory responses to carbon dioxide.

To determine the safety, efficacy, and the ventilatory responses to carbon dioxide (CO2) of epidurally administered butorphanol or morphine, 122 healthy women who underwent cesarean section with epidural anesthesia were studied. Patients were randomly assigned to receive one of four epidural regimens for the relief of postoperative pain: 5 mg morphine (n = 32), 4 mg butorphanol (n = 30), 2 mg butorphanol (n = 29), or 1 mg butorphanol (n = 31). Epidural morphine provided satisfactory analgesia with slow onset and long duration of approximately 21 hr. When butorphanol was administered, analgesia of rapid onset was seen with increasing duration and effectiveness observed with increasing dose; approximately 8 hr when using 4 mg. Sixty-two percent of the patients who received morphine had pruritus. Somnolence was the main side effect encountered in patients who received epidural butorphanol. The ventilatory response to CO2 was depressed after morphine and after 2 and 4 mg butorphanol, but the duration of depression was more prolonged after morphine. It is concluded that epidural butorphanol is effective in providing pain relief after cesarean section with minor side effects. However, patients must be observed closely because of possible respiratory depression.

Butorphanol↗

PubMed1980

Placental transfer and other physiologic studies with intravenous butorphanol in the anesthetized pregnant ewe.

In clinical evaluation, butorphanol has been used in labor pain with analgesia and newborn outcome comparable to meperidine. Only limited placental transfer studies have been done in the human. The placental transfer and effect of intravenous butorphanol (2 mg) on avrious cardiovascular parameters were determined in anesthetized sheep. Serum butorphanol was determined by a specific radioimmunoassay. Butorphanol 2 mg intravenously did not affect the measured cardiovascular parameters in either ewe or fetus. Butorphanol could be demonstrated in the fetal circulation within one minute of administration and appeared to reach equilibrium in the maternal circulation rapidly and to remain in equilibrium thereafter. A biexponential decline of butorphanol was observed in the maternal serum with a terminal elimination half-life of 50 minutes. The data suggest butorphanol distribution in the pregment ewe can be conceptualized by the two compartment model, with the fetus as part of the peripheral compartment. These studies support the clinical finding from other studies that butorphanol appears to be a safe analgesic for use in labor pain.

Anesthesia↗

PubMed1994

Drug discrimination assessment of agonist-antagonist opioids in humans: a three-choice saline-hydromorphone-butorphanol procedure.

To assess the discriminative stimulus properties of mixed agonist-antagonist opioids in humans, postaddict volunteers were trained in a three-choice drug discrimination procedure to discriminate among the effects of saline (4 ml i.m.), hydromorphone (3 mg i.m.) and butorphanol (6 mg i.m.). Subjects earned monetary reinforcement by correctly identifying the training drugs by letter code. Other subjective, behavioral and physiological measures were concurrently collected. After training, generalization curves for hydromorphone, butorphanol, pentazocine, nalbuphine and buprenorphine were determined. In generalization testing, both hydromorphone and butorphanol produced dose-related increases in hydromorphone-appropriate and butorphanol-appropriate responses, respectively, and other characteristic subjective effect measures. Nalbuphine produced dose-related increases in discrimination as butorphanol and in those subjective effect measures increased by butorphanol. Buprenorphine produced dose-related increases in discrimination as hydromorphone and in those subjective effect measures increased by hydromorphone. Pentazocine was not consistently discriminated as either butorphanol or hydromorphone. These results differ from those of previous discrimination studies using similar methods but different training drugs. Compared to a previous study in which pentazocine served as the kappa-like training drug, the use as a training drug of the more pharmacologically specific kappa-like drug butorphanol permitted greater differentiation among test drugs and yielded discrimination results more consistent with other pharmacological evidence (buprenorphine being mu-like and nalbuphine being kappa-like). There was a close relationship between results of the discrimination measures and the subjective effect measures.

Adult↗

PubMed1997

Butorphanol-mediated antinociception in mice: partial agonist effects and mu receptor involvement.

In the present experiments, we characterized the agonist and antagonist effects of butorphanol in mice. In the mouse radiant-heat tail-flick test, the mu agonists morphine and fentanyl and the kappa agonist U50,488H were fully effective as analgesics, whereas butorphanol was partially effective (producing 82% of maximal possible analgesic effect). Naltrexone was approximately equipotent in antagonizing the effects of morphine, fentanyl and butorphanol; in vivo apparent pA2 values for these naltrexone/agonist interactions were 7.5 (unconstrained). Naltrexone was approximately 10 times less potent in antagonizing the effect of U50,488H (average apparent pK(B) = 6.7). The selective mu antagonist beta-funaltrexamine (0.1-1.0 mg/kg) antagonized the effects of butorphanol in a dose-dependent insurmountable manner. Pretreatment with nor-binaltorphimine (32 mg/kg), a kappa-selective antagonist, did not reliably antagonize butorphanol, and naltrindole (20 and 32 mg/kg), a delta-selective antagonist, failed to antagonize the effects of butorphanol. Low doses of butorphanol (1.0, 1.8 or 3.2 mg/kg) caused parallel, rightward shifts in the dose-effect curve for morphine and parallel leftward shifts in the dose-effect curve for U50,488H. Taken together, the results of the present study suggest that butorphanol is a partial agonist in the mouse radiant-heat tail-flick test and that activity at mu receptors accounts for the majority of its antinociceptive effects.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1976

The pharmacology of butorphanol, a 3,14-dihydroxymorphinan narcotic antagonist analgesic.

Butorphanol, a new, totally synthetic morphinan, which is chemically related to naloxone, has been demonstrated to have both analgesic and narcotic antagonist properties. In rodent antiwrithing analgesic tests, butorphanol was 4 to 30 times more potent than morphine and dl-pentazocine, respectively. As an antagonist, butorphanol was about equivalent to nalorphine and 30 times more potent than dl-pentazocine. On the basis of the naloxone-induced mouse jumping test and the lack of substitution in withdrawn morphine-dependent mice, it is estimated that the potential for physical dependence of butorphanol will be less than that of dl-pentazocine but greater than that of nalorphine and dl-cyclazocine. Animal data also show that agonistic actions of butorphanol, such as respiratory depression and miosis, reach ceiling effects which are lower than those seen with morphine with an increase in dosage. Thus, butorphanol differed from morphine which exhibited agonist effects in a dose-related manner. Butorphanol showed weak to moderate central depressant properties at doses which were considerably higher (greater than 100 X) than those producing analgesia. Minimal cardiovascular and respiratory effects were seen with butorphanol in conscious dogs.

Analgesics↗

PubMed1993

The absolute bioavailability of transnasal butorphanol in patients experiencing rhinitis.

The absolute bioavailability (f) and pharmacokinetics of transnasal butorphanol were evaluated in patients experiencing rhinitis. In an open three-way crossover study, a single 2-mg dose of butorphanol tartrate was administered by intravenous bolus injection (Treatment A), by the transnasal route (Treatment B), or by the transnasal route with pretreatment of the vasoconstrictor, oxymetazoline (Treatment C). Plasma concentrations of butorphanol were determined using a drug specific radioimmunoassay. The pharmacokinetic parameters were derived using the noncompartmental methods. Butorphanol was rapidly absorbed after transnasal administration. The mean maximum concentrations (Cmax) for the transnasal treatment with and without pretreatment of oxymetazoline were 1.61 and 3.01 ng.ml-1, respectively. The corresponding mean absorption times (MAT) were 1.34 and 0.23 h. The mean half-life values were 5.95, 6.28, and 5.77 h, for treatments A, B, and C, respectively. The resulting mean area under the plasma concentration curve (AUC) values were 11.9, 8.6, and 8.07 ng.h.ml-1 for treatments A, B, and C, respectively. The estimates for absolute bioavailability (f) of transnasal butorphanol were 69% and 72% when administered with and without oxymetazoline, respectively. The mean CLT and Vss were 121 l.h-1 and 791 l, respectively, for the intravenous treatment. The pretreatment of oxymetazoline significantly lowered the Cmax and prolonged the absorption time of butorphanol. Although the rate of absorption of transnasal butorphanol was affected by oxymetazoline, the absolute bioavailability in rhinitis patients (72%) was similar to that found with the pretreatment of oxymetazoline (69%) and those reported in healthy volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1978

A double-blind study on the effects of butorphanol compared with morphine in balanced anaesthesia.

In a randomized double-blind trial a total of 50 consenting patients scheduled for elective surgical operations were given multiple intravenous doses of butorphanol tartrate or morphine sulphate in combination with other agents to evaluate and compare the efficacy of these drugs in balanced anaesthesia. Equipotent doses of butorphanol tartrate (mean dose 2.0 mg) or morphine sulphate (10 mg) and thiopentone were employed as induction agents followed by the standardized use of muscle relaxants to facilitate tracheal intubation. Butorphanol tartrate or morphine sulphate were then employed during maintenance of anaesthesia in repeated intravenous doses, averaging butorphanol 4.6 mg and morphine 22.8 mg per patient. Evaluation of anaesthesia showed that induction and course were smooth in 96 per cent of the patients receiving butorphanol tartrate and in 84 per cent of patients receiving morphine sulphate. The analgesic action of butorphanol appeared in every respect to approximate that of morphine sulphate, with negligible side-effects. The data demonstrate that butorphanol is a useful analgesic for use in a balanced anaesthesia technique with a low side-effect incidence.

Adult↗

PubMed1991

The physical dependence liability of butorphanol: a comparative study with morphine.

In these studies, the physical dependence liability of butorphanol, a mixed 'agonist/antagonist' opioid analgesic, was compared to that of morphine. Male, Sprague-Dawley rats received i.c.v. infusions of saline (1 microliter/h), or an equimolar dose of butorphanol or morphine (52.3 nmol/h) for 3 days. The physical dependence liabilities of these two compounds were then compared by assessing both behavioral withdrawal signs and weight loss following naloxone-precipitated withdrawal. Body weight loss was also evaluated following abrupt (cessation of infusion) withdrawal from butorphanol or morphine. In animals receiving i.c.v. infusions of butorphanol or morphine, naloxone administration (5 mg/kg s.c.) induced an equivalent degree of body weight loss compared to saline-treated animals. In addition, the ED50 of naloxone to produce wet shakes, escape behavior, teeth chattering, urination and defecation was equivalent in rats receiving butorphanol or morphine. Infusions of butorphanol or morphine also produced an equivalent degree of weight loss in animals undergoing abrupt withdrawal. These results demonstrate then that a substantial degree of physical dependence had developed in rats which received a large dose of butorphanol.

Animals↗

PubMed1989

Comparative pharmacological and biochemical studies between butorphanol and morphine.

A number of in vivo and in vitro studies were undertaken to compare the pharmacological and biochemical effects of the partial agonist, butorphanol, with that of morphine. Both compounds were equipotent antinociceptive agents in the rat tail withdrawal test. In the acetic acid writhing test butorphanol had approximately 3.5 times the antiwrithing activity on a molar basis than morphine. In a study of the effects of these compounds on body temperature, butorphanol as well as morphine produced hyperthermia after acute dosing. Additionally, butorphanol produced a profound diuresis and decrease in urine osmolality after acute administration. In contrast, morphine produced an antidiuresis throughout most of the study period with no significant changes in urine osmolality from control. Butorphanol administration had no effect on respiratory rate, while morphine markedly decreased respiratory rate. In in vitro radioligand displacement studies, butorphanol was a potent competitor against 3H-DAGO, 3H-DPDPE, and 3H(-)-EKC binding, exhibiting 3, 10, and 30 times more activity, respectively, than morphine. Both compounds were weak inhibitors of 3H-(+)-SKF 10047 binding, yielding IC50 values of in excess of 1 microM. The results indicate that butorphanol has multiple actions on the opioid receptor system, and shares similarities as well as differences in its mechanism(s) of actions with morphine.

Analgesia↗