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PubMedDate not supplied

A comparison of injectable anesthetic combinations in horses.

Six combinations of injectable anesthetic agents were administered to six adult horses in a Latin square design. The drug combinations were xylazine-ketamine, xylazine-butorphanol-ketamine, xylazine-tiletamine-zolazepam, xylazine-butorphanol-tiletamine-zolazepam, detomidine-ketamine, and detomidine-butorphanol-ketamine. Measured variables were heart rate, respiratory rate, systolic blood pressure, arterial pH (pHa), PaCO2, PaO2, recumbency time, and number of attempts necessary to stand. Quality of induction and recovery, muscle relaxation, and response to stimulus were evaluated subjectively. The horses required significantly more attempts to stand after administration of xylazine-tiletamine-zolazepam, xylazine-butorphanol-tiletamine-zolazepam, and detomidine-ketamine than after xylazine-ketamine, xylazine-butorphanol-ketamine, or detomidine-butorphanol-ketamine. Mean recumbency times varied from 23.0 minutes with xylazine-ketamine to 41.3 minutes with xylazine-butorphanol-tiletamine-zolazepam. There were significant differences in mean heart rates at minute 15, mean respiratory rates at minutes 5, 10 and 15, and mean systolic blood pressures at minute 10 of anesthesia. There were no significant differences in pHa, PaCO2 or PaO2.

Acid-Base Equilibrium↗
PubMed1993

Influence of anesthetic regimens on the perioperative catecholamine response associated with onychectomy in cats.

Plasma catecholamine concentrations in response to onychectomy were examined in 27 cats receiving different anesthetic regimens. Each cat was anesthetized with a dissociative-tranquilizer combination, and onychectomy was performed on 1 forefoot. One week later, each cat was anesthetized with the same dissociative-tranquilizer combination plus either butorphanol or oxymorphone, and onychectomy was performed on the other forefoot. Four treatment groups were studied: tiletamine-zolazepam and tiletamine-zolazepam-butorphanol combinations were administered to group-1 cats, ketamine-acepromazine and ketamine-acepromazine-butorphanol combinations were administered to group-2 cats, tiletamine-zolazepam and tiletamine-zolazepam-oxymorphone combinations were administered to group-3 cats, and ketamine-acepromazine and ketamine-acepromazine-oxymorphone combinations were administered to group-4 cats. All drug combinations were administered IM. Central venous blood samples were drawn for catecholamine analysis after injection of drug(s), after onychectomy, and 1, 2, and 4 hours after injection. Tiletamine-zolazepam alone or tiletamine-zolazepam-butorphanol prevented epinephrine release for 2 hours after injection of drug(s). Norepinephrine concentration increased significantly (P < 0.05) from baseline after onychectomy for tiletamine-zolazepam-butorphanol and at 4 hours for tiletamine-zolazepam and tiletamine-zolazepam-butorphanol. After onychectomy, there was no difference in epinephrine values between tiletamine-zolazepam and tiletamine-zolazepam-oxymorphone. Ketamine-acepromazine prevented increases in norepinephrine and epinephrine concentrations for up to 2 hours after surgery. Addition of butorphanol to ketamine-acepromazine decreased norepinephrine values immediately after onychectomy. Addition of oxymorphone to ketamine-acepromazine resulted in lower epinephrine values 4 hours after surgery.

Anesthesia, General↗
PubMed2002

Focal kappa-opioid receptor-mediated dependence and withdrawal in the nucleus paragigantocellularis.

The nucleus paragigantocellularis (PGi) has been hypothesized to play an important role in the development of physical dependence on opioids, including the prototype mu-opioid receptor agonist, morphine, and the mixed agonist/antagonist, butorphanol, which shows selective kappa-opioid receptor agonist activity, in rats. In confirmation of previous work, electrical stimulation of the PGi in opioid-nai;ve rats induced stimulus-intensity-related, withdrawal-like behaviors similar to those observed during naloxone-precipitated withdrawal from dependence upon butorphanol. Novel findings were made in rats surgically implanted with cannulae aimed at the lateral ventricle and the right PGi and made physically dependent by intracerebroventricular infusion of either morphine (26 nmol/microl/h) or butorphanol (26 nmol/microl/h) through an osmotic minipump for 3 days. Two hours following termination of the opioid infusion, microinjections of naloxone (11 nmol/400 nl), a nonselective opioid receptor antagonist, or nor-binaltorphimine (nor-BNI) (3.84 nmol/400 nl), a selective kappa-opioid receptor antagonist, were made into the PGi of morphine-dependent and butorphanol-dependent rats. Discrete PGi injections precipitated withdrawal behaviors, with significant (P<.05) increases noted in the incidence of teeth chattering, wet-dog shakes, and scratching. Composite scores for behavioral withdrawal were significantly higher in nor-BNI-precipitated, butorphanol-dependent rats (score=6.8+/-0.6), in naloxone-precipitated, butorphanol-dependent rats (8.9+/-0.8), and in naloxone-precipitated, morphine-dependent rats (11.5+/-0.9) than in all other groups. Both kappa- and mu-opioid receptor mediated dependence can be demonstrated at the level of a discrete medullary site, the PGi, which further supports a specific role for this nucleus in elicitation of behavioral responses during opioid withdrawal.

Animals↗
PubMed1992

Action of opioid agonist-antagonist drugs on the pupil and nociceptive responses in mice.

Opioid derivatives with mixed agonist-antagonist activities are becoming increasingly more popular in analgesia. We tested the mydriatic and analgesic activity of morphine in mice in comparison with similar effects of three agonist-antagonist agents: buprenorphine, butorphanol and nalbuphine. We also examined the antagonistic action of these three drugs by evaluating the analgesia and mydriasis in animals pretreated with morphine. The analgesic effect was assayed using the hot plate method while the pupillary responses were measured with a binocular operating microscope. Morphine produced dose-dependent mydriasis and analgesia in mice. The morphine-type agent buprenorphine and two nalorphine-type agonist-antagonists, butorphanol and nalbuphine, caused agonistic mydriatic and analgesic effects, usually less effective then morphine. Buprenorphine proved to have higher agonist activity than butorphanol and nalbuphine. The difference between butorphanol and nalbuphine was not statistically significant. A correlation between the mydriatic and the analgesic activity, known to exist among opioid derivatives with agonist activity only, was also demonstrated in the three investigated agonist-antagonist agents. Morphine-induced mydriasis and analgesia were reversed by all three agonist-antagonist drugs, but buprenorphine is a significantly weak antagonist in comparison with butorphanol and nalbuphine. An antagonistic property (antimydriatic and antianalgesic effects after pretreatment with morphine) of both nalorphine-type investigated drugs was not statistically significant, except for the antianalgesic effect of nalbuphine in doses 1 and 3 mg.kg(-1), which was higher in comparison with butorphanol.

Journal Article↗
PubMed1991

Opioid agonist-antagonist drugs in acute and chronic pain states.

The agonist-antagonist opioid analgesics are a heterogeneous group of drugs with moderate to strong analgesic activity comparable to that of the pure agonist opioids such as codeine and morphine but with a limited effective dose range. The group includes drugs which act as an agonist or partial agonist at one receptor and an antagonist at another (pentazocine, butorphanol, nalbuphine, dezocine) and drugs acting as a partial agonist at a single receptor (buprenorphine). These drugs can be classified as nalorphine-like or morphine-like. Meptazinol does not fit into either classification and occupies a separate category. Pentazocine, butorphanol and nalbuphine are weak mu-antagonists and kappa-partial-agonists. All three drugs are strong analgesics when given by injection: pentazocine is one-sixth to one-third as potent as morphine, nalbuphine is slightly less potent than morphine, and butorphanol is 3.5 to 7 times as potent. The duration of analgesia is similar to that of morphine (3 to 4 hours). Oral pentazocine is closer in analgesic efficacy to aspirin and paracetamol (acetaminophen) than the weak opioid analgesics such as codeine. Neither nalbuphine nor butorphanol is available as an oral formulation. At usual therapeutic doses nalbuphine and butorphanol have respiratory depressant effects equivalent to that of morphine (though the duration of such effects with butorphanol may be longer). Unlike morphine there appears to be a ceiling to both the respiratory depression and the analgesic action. All of these 3 drugs have a lower abuse potential than the pure agonist opioid analgesics such as morphine. However, all have been subject to abuse and misuse, and pentazocine (but not the others) is subject to Controlled Drug restrictions. Buprenorphine is a potent partial agonist at the mu-receptor, and by intramuscular injection is 30 times as potent as morphine. A ceiling to the analgesic effect of buprenorphine has been demonstrated in animals and it is also claimed in humans. However, there are no reliable data available to define the maximal dose of buprenorphine in humans. A practical ceiling exists for sublingual use in that the only available formulation is a 2 micrograms tablet and few patients will accept more than 3 or 4 of these in a single dose. The duration of analgesia is longer than that of morphine, at 6 to 9 hours. There have been suggestions that buprenorphine causes less respiratory depression than morphine, but viewed overall it appears that in equianalgesic doses the 2 drugs have similar respiratory depressant effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Analgesics↗
PubMed2002

Antinociceptive effects of the selective delta opioid agonist SNC80 alone and in combination with mu opioids in the squirrel monkey titration procedure.

RATIONALE: The nonpeptidic compound SNC80 [(+)-4[(alphaR)-alpha-((2S, 5R)-4-allyl-2, 5,-dimethyl-l-piperazinyl)-3-methoxybenzyl]- N, N-diethylbenzamide], has a high degree of selectivity for delta opioid receptors. Moreover, compounds with delta opioid activity have been shown to enhance the effects of mu agonists under certain conditions. OBJECTIVES: The present study examined the effects of SNC80 alone and in combination with the mu opioid agonists, morphine, butorphanol, and buprenorphine to determine whether SNC80 would enhance their antinociceptive effects. METHODS: In the squirrel monkey shock titration procedure increasing levels of shock are delivered to the monkey's tail in incremental steps and responses on a lever decrease shock intensity. The level at which monkeys maintain the shock (median shock level, MSL) and rate of responding (RR) are examined. RESULTS: SNC80 alone did not consistently alter responding under the titration procedure; however, morphine, butorphanol, and buprenorphine increased MSL without decreasing RR markedly. SNC80 (0.1-3.0 mg/kg) enhanced the effects of single doses of morphine, butorphanol, and buprenorphine that either did not increase or produced very small increases in MSL when administered alone. Interestingly, SNC80 enhanced the effects of morphine, butorphanol, and buprenorphine on MSL without decreasing RR. CONCLUSIONS: SNC80 does not produce antinociceptive effects in the squirrel monkey titration procedure but can enhance the effects of selected doses of morphine, butorphanol, and buprenorphine on MSL without decreasing RR. These data suggest that SNC80-induced enhancement of the antinociceptive effects of mu opioids is dependent on dose, time, and method of administration and is not the result of sedation or motor dysfunction.

Analgesics↗
PubMed1997

Increased release of excitatory amino acids in rat locus coeruleus in kappa-opioid agonist dependent rats precipitated by nor-binaltorphimine.

Extracellular fluid levels of glutamate and aspartate in the locus coeruleus (LC) during nor-binaltorphimine (nor-BNI)-precipitated withdrawal from butorphanol, (5alpha,7alpha,8beta)-(+)-N-methyl-N-[7-(1-pyrrolidiny l)-1-oxaspiro [4,5] dec-8-yl]-benzeneacetamide (U-69,593), or morphine were measured in rats. When the microdialysis probe was located in the core of the LC, increases in glutamate and aspartate were noted after nor-BNI (48 nmol/50 microl, LC)-precipitated withdrawal in rats that had been intracerebroventricularly infused with butorphanol (26 nmol/1 microl/h) or U-69,593 (26 nmol/10 microl/h) for 3 days. The glutamate and aspartate levels in the LC markedly increased in the butorphanol- or U-69,593-dependent rats within 60 min following administration of nor-BNI. However, there was no significant increase in levels of glutamate, and only a slight increase in levels of aspartate, after nor-BNI treatment of the morphine (26 nmol/1 microl/h)-infused rats. Behavioral signs of withdrawal (teeth-chattering, wet-dog shakes, etc.) were observed following nor-BNI challenge in the butorphanol- or U-69,593-infused rats, with only minimal signs in the morphine-infused rats, and none in the saline-infused controls. These results directly suggest that kappa-opioid receptors and excitatory amino acids within the LC mediate withdrawal in animals dependent on butorphanol or U-69,593, but not on morphine.

Animals↗
PubMed1996

Precipitated kappa-opioid receptor agonist withdrawal increase glutamate in rat locus coeruleus.

Extracellular fluid levels of excitatory amino acids (glutamate, Glu; and aspartate, Asp) in the locus coeruleus and the behavioral signs during naloxone-precipitated withdrawal from kappa-opioid receptor agonists, butorphanol and (5 alpha, 7 alpha, 8 beta) -(+)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4,5]dec-8-yl]-be nzaneacetamide (U-69,593), were investigated by in vivo microdialysis. Increases in levels of Glu, but not of Asp, were noted after naloxone (12 or 48 nmol/5 microliters, locus coeruleus)-precipitated withdrawal in the rats which had been intracerebroventricularly infused with butorphanol (26 nmol/1 microliters/h) or U-69,593 (26 nmol/10 microliters/h) for 3 days. The Glu levels in the locus coeruleus increased following administration of naloxone before and during the first 15-min sample after the precipitation of withdrawal in the butorphanol- or U-69,593-dependent rats. Furthermore, behavioral evidence of withdrawal (teeth-chattering, wet-dog shakes, etc.) was detected following the naloxone challenge in the butorphanol- and U-69,593-infused rats, but not in saline-infused controls. These results provide direct evidence to support the role of excitatory amino acids within the locus coeruleus in butorphanol or U-69,593 withdrawal.

Analgesics↗
PubMed1990

Chloroprocaine antagonism of epidural opioid analgesia: a receptor-specific phenomenon?

Sixty healthy patients scheduled for elective cesarean delivery under epidural anesthesia were randomized to receive either lidocaine or 2-chloroprocaine as the primary local anesthetic agent. When patients first complained of postoperative pain in the recovery room, they were given either fentanyl 50 micrograms or butorphanol 2 mg, epidurally, in a randomized, blinded fashion. Postoperative analgesia, quantitated on a visual analogue scale, as well as time elapsed until first request for supplemental opioid, did not differ for patients receiving butorphanol after either 2-chloroprocaine or lidocaine anesthesia. In contrast, epidural fentanyl produced a shorter and lesser degree of sensory analgesia after 2-chloroprocaine use, whereas epidural fentanyl after lidocaine anesthesia provided pain relief similar to that seen in the butorphanol groups. Side effects were limited to somnolence with butorphanol and pruritus with fentanyl. No evidence of respiratory depression was seen in any patient. We conclude that 2 mg of butorphanol epidurally provides approximately 2 to 3 h of effective analgesia after cesarean delivery with either lidocaine or 2-chloroprocaine anesthesia. Epidural fentanyl seems to be antagonized when 2-chloroprocaine, but not lidocaine, is used as the primary local anesthetic agent. We suggest a possible mu-receptor-specific etiology for this effect.

Adult↗
PubMed1994

Assessment of the relative intrinsic efficacy of profadol and meperidine in a pigeon drug discrimination procedure: relevance to partial substitution patterns.

Substitution and antagonism patterns of butorphanol, meperidine and profadol were examined in pigeons trained to discriminate either a 0.056 (low) or 0.18 (high) mg/kg dose of fentanyl from saline. In the low-dose group, fentanyl, meperidine, profadol and butorphanol substituted completely (>/=85% fentanyl-appropriate responding) for the fentanyl stimulus. For fentanyl and butorphanol, complete substitution was obtained at doses that had little effect on rates of responding, whereas profadol substituted at doses that moderately decreased rates and meperidine substituted at doses that markedly decreased rates. Although naloxone antagonized the stimulus effects of meperidine and profadol, it failed to alter their rate-decreasing effects. In the high-dose group, fentanyl and butorphanol substituted completely and meperidine and profadol partially (approximately 50% fentanyl-appropriate responding) for the fentanyl stimulus. During antagonism tests, meperidine and profadol produced only small decreases (less than 15%) in the percentage of fentanyl-appropriate responding produced by the training dose of fentanyl. Analysis of individual data indicated that meperidine and profadol produced three patterns of substitution and antagonism. In one subgroup of pigeons, meperidine and profadol substituted completely for but failed to antagonize the fentanyl stimulus; in another, these opioids failed to substitute for but did antagonize the fentanyl stimulus; and in another, these opioids failed to substitute for or antagonize the fentanyl stimulus. In this latter subgroup, meperidine and profadol produced leftward shifts in the dose-effect function for the stimulus effects of fentanyl and butorphanol. The present findings suggest that the failure of meperidine and profadol to substitute completely for the high-dose fentanyl stimulus was a direct consequence of their rate-decreasing effects rather than low efficacy at the mu receptor.

Journal Article↗
PubMed2005

Social and environmental influences on opioid sensitivity in rats: importance of an opioid's relative efficacy at the mu-receptor.

RATIONALE: Evidence indicates that social and environmental enrichment can influence the functional maturation of the central nervous system and may affect an organism's sensitivity to centrally acting drugs. OBJECTIVE: The purpose of the present study was to examine the effects of social and environmental enrichment on sensitivity to mu-opioids possessing a range of relative efficacies at the mu-receptor. METHODS: Rats were obtained at weaning (21 days) and divided into two groups immediately upon arrival. Isolated rats were housed individually in opaque laboratory cages with no visual or tactile contact with other rats; enriched rats were housed socially in groups of four in large cages and given various novel objects on a daily basis. After 6 weeks under these conditions, the effects of morphine, levorphanol, buprenorphine, butorphanol, and nalbuphine were examined in the warm-water, tail-withdrawal procedure and the place-conditioning procedure. RESULTS: In the tail-withdrawal procedure, isolated and enriched rats did not differ in sensitivity to morphine (1.0-30 mg/kg) and levorphanol (0.3-10 mg/kg), but enriched rats were more sensitive to buprenorphine (0.03-3.0 mg/kg), butorphanol (0.3-30 mg/kg), and nalbuphine (0.3-30 mg/kg). In drug combination tests, butorphanol and nalbuphine antagonized the effects of morphine in isolated rats under conditions in which they produced high levels of antinociception in enriched rats. In the place-conditioning procedure, doses of 10 morphine and 3.0 levorphanol established a place preference in both groups of rats, whereas doses of 0.3 buprenorphine, 3.0 butorphanol, and 10 nalbuphine established a place preference only in enriched rats. CONCLUSIONS: These findings may be taken as evidence that enriched rats are more sensitive than isolated rats to the effects of lower-efficacy mu-opioids and that social and environmental enrichment leads to functional alterations in opioid receptor populations.

Analgesics, Opioid↗
PubMed1997

Modulating effects of a cold water stimulus on opioid effects in volunteers.

The purpose of this study was to characterize the effect of a painful stimulus on morphine and butorphanol effects in healthy non-drug abusing volunteers. Thirteen subjects with no history of opiate dependence participated in a randomized, placebo-controlled, double-blind, crossover trial in which each subject received saline, 2 mg/70 kg butorphanol, and 10 mg/70 kg morphine, IV, in each of two conditions, periodic forearm immersions into either ice-cold water (2 degrees C) or into warm water (37 degrees C). Both opioids reduced self-reported ratings of pain intensity, indicative of analgesia. Several of the subjective effects of morphine were attenuated either during or in between cold-water immersions, including visual analog scale ratings of "coasting (spaced out)," "high (drug "high")," "sleepy (drowsy, tired)," and "lightheaded". In contrast, some of butorphanol's subjective effects were increased by the cold-water manipulation. Morphine impaired psychomotor performance during one of the warm-water immersions, but not during the cold-water immersions. Psychomotor impairment induced by butorphanol was not affected by water temperature. This study provides evidence that opioid effects can be modulated by a painful stimulus in humans.

Adult↗
PubMed1995

Possible involvement of protein kinases in physical dependence on opioids: studies using protein kinase inhibitors, H-7 and H-8.

Effects of a cAMP-dependent protein kinase and protein kinase C inhibitor, H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine) and a cAMP- and cGMP-dependent protein kinase inhibitor, H-8 (N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide), on the behavioral signs of naloxone (an opioid receptor antagonist)-precipitated withdrawal syndrome and effects of H-7 on the change of protein kinase C activity in the pons/medulla region induced by morphine (a mu-opioid receptor agonist) or butorphanol (a mu/delta/kappa mixed opioid receptor agonist) were investigated in this study. Rats were intracerebroventricularly (i.c.v.) infused with morphine (26 nmol/microliters/h) or butorphanol (26 nmol/microliters/h) through osmotic minipumps for 3 days. In some groups, either saline or drug-treated groups were concomitantly infused with H-7 (1 and 10 nmol/microliters/h) or H-8 (10 nmol/microliters/h). The expression of physical dependence produced by morphine or butorphanol, as evaluated by naloxone (5 mg/kg i.p.)-precipitated withdrawal signs, was reduced by concomitant infusion of H-7 or H-8. In the same condition, morphine and butorphanol chronic treatment enhanced (28.1% and 26.3% enhancement over the saline-treated group, respectively) cytosolic protein kinase C activity in the pons/medulla, but not in the membrane fraction. Furthermore, concomitant infusion of H-7 inhibited the enhancement of protein kinase C activity. These results indicate that various types of protein kinases may play an important role in the development and/or expression of physical dependence on opioids. Among them, the enhancement of cytosolic protein kinase C activity in the pons/medulla region seems to be one of the major underlying mechanisms in opioid physical dependence.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Cardiovascular and respiratory effects of tiletamine-zolazepam.

The combination of tiletamine and zolazepam is an important dissociative anesthetic-tranquilizer. However, little is known about the effects of this combination on the heart and respiration in rats. Adult, male rats anesthetized with tiletamine-zolazepam alone or tiletamine-zolazepam combined with xylazine or butorphanol were evaluated for changes in heart rate, mean arterial blood pressure, arterial blood pH, and blood gases during a 75-min period of anesthesia. Rats anesthetized with tiletamine-zolazepam had increased mean arterial blood pressure and less respiratory depression than did rats anesthetized with sodium pentobarbital. Tiletamine-zolazepam combined with xylazine at either dose produced bradycardia and a marked hypotension that persisted throughout the 75-min period. This combination produced respiratory depression comparable to tiletamine-zolazepam alone. The addition of butorphanol to tiletamine-zolazepam caused a transient hypotension and bradycardia. Tiletamine-zolazepam plus butorphanol produced a mild to severe respiratory depression that was dose and time dependent. These results demonstrate that: a) Tiletamine-zolazepam is cardiostimulatory, a property consistent with the known cardiovascular effects of other dissociative anesthetics; b) xylazine plus tiletamine-zolazepam is a potent cardiovascular depressant combination; and c) tiletamine-zolazepam plus butorphanol at specific doses is an anesthetic-analgesic combination with minimal effects on cardiovascular and respiratory function.

Anesthetics, Dissociative↗
PubMed1997

Tolerance and cross tolerance to the accuracy- and rate-decreasing effects of mu opioids in rats responding under a fixed-consecutive-number schedule.

The purpose of the present investigation was to examine the development of tolerance to the effects of morphine and other mu opioids in rats responding under a fixed-consecutive-number (FCN) schedule of food presentation. To this end, five rats were trained under an FCN schedule and subsequently tested with a variety of mu opioids both before and during chronic exposure to a 0.4 mg/ml morphine drinking solution. Morphine, fentanyl, buprenorphine, butorphanol and nalbuphine produced dose-dependent decreases in both accuracy and response rate when tested prior to the chronic regimen. In most instances, doses of these drugs that decreased accuracy also decreased response rate. During chronic treatment, tolerance developed to the effects of morphine and cross-tolerance was conferred to the effects of fentanyl, buprenorphine and butorphanol. A greater degree of tolerance was conferred to the effects of butorphanol than to the other opioids examined, and the degree of tolerance conferred to butorphanol's rate-decreasing effects was greater than the degree of tolerance conferred to its accuracy-decreasing effects. Doses of naloxone that had no effect prior to morphine treatment produced large decreases in accuracy and response rate when tested during the chronic regimen. In contrast to the other opioids examined, the potency of nalbuphine was not altered by chronic morphine administration. These data emphasize the importance of both pharmacological and procedural variables in the development of tolerance and cross tolerance to the behavioral effects of opioids.

Animals↗
PubMed1998

Drug discrimination history: pigeons trained to discriminate opioids with activity at different receptor types.

In pigeons (Columba livia; N = 5) trained to discriminate the mu (mu) opioid butorphanol from saline, various mu (morphine, fentanyl) but not kappa (kappa; bremazocine, U50,488, U69,593) opioids produced at least 80% drug-appropriate responding. Subsequently, pigeons were retrained to discriminate the kappa opioid bremazocine from saline; in this condition, both mu and kappa opioids produced at least 80% drug-appropriate responding, naloxone was more potent as an antagonist of the butorphanol stimulus, and chronic bremazocine treatment selectively produced tolerance to the bremazocine stimulus. Although butorphanol can function as a kappa antagonist, the effects produced by combinations of butorphanol and bremazocine during training with bremazocine were generally effect-additive. The findings indicate that the mechanisms underlying the stimulus effects of mu opioids are not altered by subsequent training with a kappa opioid. Conversely, a history of discrimination training with a mu opioid does not alter the discriminative control produced by kappa opioids during subsequent training with a kappa opioid.

Animals↗
PubMed2004

Sex differences in analgesia: a randomized trial of mu versus kappa opioid agonists.

OBJECTIVES: We sought to evaluate whether there is a sex difference in the analgesic response to mu versus kappa opioids in the management of acute moderate to severe pain of injury in the emergency department. METHODS: The study was a randomized, double-blind, clinical trial comparing the prototypical mu-receptor agonist, morphine sulfate, to the prototypical kappa agonist, butorphanol. The primary endpoints were degree of relief by visual analog scores at 30 and 60 minutes. Statistical analysis was performed using Mann-Whitney Utest for nonparametric analysis and repeated-measures analysis of variance. RESULTS: Ninety-four patients were entered in the study, with 49 (52%) males and 45 (48%) females. Forty-six received morphine sulfate and 48 received butorphanol. There was no difference in demographics in the two groups. At 60 minutes, females had significantly lower visual analog scores with butorphanol compared with morphine (P = 0.046). At 60 minutes, there was a trend for a difference in response of males versus females to morphine, with males responding better than females (P = 0.06). CONCLUSION: Females had better pain scores with butorphanol than morphine at 60 minutes.

Adult↗
PubMed2004

The effect of four anesthetic protocols on splenic size in dogs.

OBJECTIVE: To characterize the effects of four anesthetic protocols on the size of the spleen during surgery in dogs. STUDY DESIGN: Prospective experimental trial. ANIMALS: Twenty-four beagle dogs, 1.1 +/- 0.3 years of age and weighing 10.9 +/- 2.7 kg. METHODS: Dogs were allocated to receive one of four anesthetic protocols: 1 - pre-medication with acepromazine and butorphanol, induction with thiopental; 2 - pre-medication with acepromazine and butorphanol, induction with propofol; 3 - pre-medication with medetomidine and butorphanol, induction with propofol; and 4 - pre-medication with medetomidine and butorphanol, induction with ketamine and diazepam. Anesthesia was then maintained with halothane. At laparotomy, the spleen length, width, and height were measured, these were measured again just prior to closure of the abdomen. Splenic area and volume were calculated. Hematocrit and total serum protein (TSP) were measured before and after induction and during laparotomy. RESULTS: Splenic volume was greatest after protocol 4 (161.2 +/- 40.2 cm(3); p < 0.05) and was least after protocol 2. The differences in volume were because of differences in length, width, and height between groups. There was no significant change in area, length, or width over the study period. Hematocrit decreased significantly in all dogs but at different times. The decrease occurred after pre-medication if acepromazine was administered, at induction following protocol 3 and during surgery following protocol 4. CONCLUSIONS: If splenic volume is to be minimized during surgery, then acepromazine and propofol should be used in the anesthetic protocol. The administration of medetomidine, diazepam, and ketamine will produce a greater splenic volume. Lack of correlation between hematocrit and spleen size following the anesthetic protocols studied suggests sequestration of red blood cells in nonsplenic sites.

Acepromazine↗