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At least 19 recordsLinked to original sources

PubMed2002

The analgesic effect of nalbuphine and its long-acting prodrug, nalbuphine pivalate, in rats.

BACKGROUND: Nalbuphine is an opioid-analgesic with agonist-antagonist properties. Recently, we have synthesized a nalbuphine prodrug, nalbuphine pivalate. The aim of the present study was to evaluate the analgesic effect and the analgesic duration of this prodrug. METHODS: Forty-eight male Sprague-Dawley rats (4 groups, n = 12 in each group) were used. Rats in group 1 received nalbuphine HCl 25 mumol/kg (in saline) intramuscular injection; rats in group 2 received nalbuphine pivalate 25 mumol/kg (in sesame oil) intramuscular injection, whereas those in groups 3 and 4 received saline and sesame oil respectively. The analgesic effects of testing agents were evaluated using the cold ethanol tail-flick test (-30 degrees C). RESULTS: Both nalbuphine HCl and nalbuphine pivalate demonstrated significant analgesic effects. The analgesic duration of nalbuphine HCl was 2 h while that of nalbuphine pivalate was 30 h. CONCLUSIONS: Nalbuphine pivalate has a very long duration of analgesic action. This fascinating finding is worth further evaluation.

Analgesics, Opioid↗

PubMed2002

Minidose lidocaine-fentanyl spinal anesthesia in ambulatory surgery: prophylactic nalbuphine versus nalbuphine plus droperidol.

UNLABELLED: Minidose lidocaine-fentanyl spinal anesthesia (SAB(MLF)) is a safe, effective, and efficient anesthetic for ambulatory surgery. Unfortunately, it has a frequent incidence of pruritus and a substantial incidence of nausea and vomiting. Nalbuphine is effective in treating or preventing pruritus after intrathecal or epidural morphine but may or may not have a beneficial effect on nausea and vomiting. Droperidol has demonstrated antiemetic efficacy with neuraxial opiates. In this study, we examined the prophylactic use of nalbuphine alone compared with nalbuphine with droperidol after SAB(MLF). One-hundred-twenty-four patients having outpatient knee arthroscopy under SAB(MLF) with 20 mg of lidocaine 0.5% and 20 micro g of fentanyl were randomized to receive IV at the end of surgery either 4 mg of nalbuphine (Group N) or droperidol 0.625 mg plus nalbuphine 4 mg (Group ND). The incidences of early (before discharge) and late onset nausea were, respectively, 18% versus 5% and 32% versus 13%. The postoperative incidences of pruritus were 61% versus 40%, whereas 19% of patients in Group N compared with 2% of patients in Group ND requested treatment for this. Group ND had lower pain scores and had a longer delay until first use of analgesic. There were no differences in average times to discharge. The only side effect of the medications was an increased drowsiness in Group ND. In conclusion, as prophylactic medication for use in conjunction with SAB(MLF), the addition of droperidol 0.625 mg to nalbuphine 4 mg was superior to nalbuphine alone. The combination provided for reduced postoperative nausea, pruritus, and pain-benefits that persisted after discharge home. The combination also avoided isolated cases of extreme delay in discharge. IMPLICATIONS: Droperidol in combination with nalbuphine enhances analgesia and is more effective than nalbuphine alone in preventing pruritus, nausea, and vomiting after minidose lidocaine-fentanyl spinal anesthesia.

Adult↗

PubMed2001

Transdermal delivery of nalbuphine and nalbuphine pivalate from hydrogels by passive diffusion and iontophoresis.

The objective of this study was to evaluate the in vitro transdermal permeation of nalbuphine hydrochloride (CAS 23277-43-2) (NA) and nalbuphine pivalate (NAP), a novel prodrug of NA, from different hydrogel formulations under passive diffusion as well as iontophoresis. Various concentrations of polymers, including polyvinylpyrrolidone (PVP) and hydroxypropyl cellulose (HPC) were used in the hydrogel formulations. The passive permeation rate of NA was affected by the polymer concentrations, which can be attributed to different viscosities of the hydrated formulations; whereas the passive permeation rate of NAP was not influenced by the various polymer concentrations. Iontophoresis significantly increased the permeation rates of NA and NAP from various hydrogel formulations through skin; the enhancement ratios were higher for NA in all the formulations studied. The iontophoretic permeation rates of NA were slightly decreased by the incorporation of polymers; however, the transdermal flux and membrane potential were independent of polymer concentrations for both NA and NAP, demonstrating that the polymer concentrations in the hydrogel formulations did not have significant effects on the iontophoretic permeation of NA and NAP.

Administration, Cutaneous↗

PubMed1987

Nalbuphine for obstetric analgesia. A comparison of nalbuphine with pethidine for pain relief in labour when administered by patient-controlled analgesia (PCA).

A double-blind, randomised study of 60 patients who received intravenous increments of nalbuphine 3 mg or pethidine 15 mg by patient-controlled analgesia during the first stage of labour, was carried out. Pain intensity, sedation, uterine contractions, maternal cardioventilatory variables and fetal heart rate were recorded as well as any side effects. Apgar scores, time to sustained respiration and resuscitative measures required for the neonate were noted at delivery. Modified neonatal neurobehavioural studies and a retrospective assessment of maternal analgesia, satisfaction and tolerance were also carried out. Group mean values of pain scores of nalbuphine-medicated primiparous women were statistically significantly lower than those of pethidine-medicated patients (p less than 0.01). Other assessments did not demonstrate a statistical significance between the two groups.

Adult↗

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↗

PubMed2003

Dose ratio is important in maximizing naloxone enhancement of nalbuphine analgesia in humans.

The analgesic effect of kappa partial agonist opioids (i.e. nalbuphine, pentazocine and butorphanol) is significantly greater in women. Recent evidence suggests that this sexual dimorphism may result from a naloxone-sensitive anti-analgesic effect that is activated along with, and summates with, the analgesic effect of these agents, resulting in decreased analgesia or increased pain. For example, nalbuphine (5 mg) produces profound anti-analgesia (i.e. enhanced pain) in men, but addition of a low dose of the opioid receptor antagonist naloxone (0.4 mg, opioid antagonist) induces significant analgesia in men and enhances nalbuphine analgesia in women. To further delineate the dose-dependent relationship of nalbuphine and naloxone, we recently evaluated the effect of a lower dose of nalbuphine (2.5 mg) with and without naloxone (0.4 mg) on dental postoperative pain. In women, nalbuphine alone induced modest short duration analgesia, which was antagonized by the addition of naloxone. In men, this dose of nalbuphine alone did not produce analgesia or anti-analgesia, and naloxone did not alter the response to nalbuphine. Thus, it appeared that the 2.5 mg dose of nalbuphine was not sufficient to induce anti-analgesia while the 0.4 mg dose of naloxone was able to antagonize the analgesic effect of nalbuphine, at least in women. In the current study, we tested the hypothesis that an important determinant of naloxone enhancement of nalbuphine analgesia is the dose ratio of nalbuphine to naloxone. Since a dose ratio of 12.5:1 (i.e. 5 mg nalbuphine:0.4 mg naloxone) resulted in analgesic enhancement, but a dose ratio of 6.25:1 (2.5 mg:0.4 mg) did not, we tested the same, lower, dose of nalbuphine (2.5 mg) in combination with a lower dose of naloxone (0.2 mg) to maintain the 12.5:1 dose ratio. This lower dose of naloxone significantly prolonged the analgesic effect of nalbuphine in both men and women, suggesting that the anti-analgesic effect of nalbuphine is present in both sexes at the 2.5 mg dose and that the dose ratio of nalbuphine to naloxone is an important determinant of the analgesic efficacy of this combination.

Adult↗

PubMed2005

Effects of the mixed mu/kappa opioid nalbuphine on cocaine-induced changes in subjective and cardiovascular responses in men.

Kappa opioid agonists functionally antagonize some abuse-related and locomotor effects of cocaine, and reduce cocaine self-administration by rhesus monkeys. We compared the cardiovascular and subjective effects of acute doses of the mu/kappa opioid nalbuphine alone (5 mg/70 kg, intravenous (i.v.)), with cocaine alone (0.2 mg/kg, i.v.), and with nalbuphine+cocaine in combination, under placebo-controlled, double-blind conditions. Subjects met American Psychiatric Association Diagnostic and Statistical Manual (DSM-IV) criteria for current cocaine abuse. Nalbuphine serum levels exceeded 50 ng/ml within 10 min after injection, and cocaine plasma levels exceeded 130 ng/ml within 4 min. Cocaine's pharmacokinetic profile did not change after concurrent nalbuphine administration. The nalbuphine+cocaine combination was safe and without synergistic effects on heart rate and systolic or diastolic blood pressure. Moreover, the addition of cocaine did not increase the subjective effects of nalbuphine. Visual Analog Scale (VAS) ratings of High, Euphoria, Stimulated, and Good Effect were equivalent after nalbuphine+cocaine and nalbuphine alone, and both were significantly higher than after cocaine alone (area under the curve analysis) (p<0.05-0.01). Peak VAS ratings of High, Stimulated, Good Effect, and Drug Effect were also significantly higher after nalbuphine+cocaine than after cocaine alone (p<0.01). Addiction Research Center Inventory (ARCI) scores were equivalent for nalbuphine+cocaine and nalbuphine alone, but the PCAG, MBG, and amphetamine scores were significantly higher after both nalbuphine+cocaine and nalbuphine alone than after cocaine alone (p<0.01-0.003). Thus, there were no additive interactions between nalbuphine and cocaine on cardiovascular, subjective, or drug level measures after acute administration.

Analgesics, Opioid↗

PubMed1999

Discriminative stimulus effects of nalbuphine in nontreated and morphine-treated pigeons.

In the present study, the stimulus effects of the low efficacy agonist nalbuphine were examined under two conditions: nontreated and morphine treated. In the first experiment, five pigeons were trained to discriminate among 3.2 mg/kg morphine, 5.6 mg/kg nalbuphine, and saline. Nalbuphine produced nalbuphine-like responding. Low doses of morphine produced nalbuphine-like responding, whereas high doses produced morphine-like responding. Naltrexone produced saline-like responding and reversed the stimulus effects produced by the training doses of morphine and nalbuphine. Five different pigeons were treated daily with 10 mg/kg morphine (i.m.) and trained 6 h later to discriminate among 10 mg/kg morphine, 1.0 mg/kg nalbuphine and saline. In these pigeons, morphine produced morphine-like responding and nalbuphine produced nalbuphine-like responding. Morphine abstinence produced nalbuphine-like responding that was reversed by morphine. Additionally, naltrexone produced nalbuphine-like responding. These data suggest that the discrimination between morphine and nalbuphine in the nontreated and morphine-treated pigeons may be based on the relative efficacy differences between morphine, a higher efficacy mu-agonist, and nalbuphine a lower efficacy mu-agonist.

Analgesics, Opioid↗

PubMed1993

Discriminative-stimulus effects of the low efficacy mu agonist nalbuphine.

The discriminative stimulus effects of nalbuphine were studied in 15 male Sprague-Dawley rats trained to discriminate 3.2 mg/kg of nalbuphine from saline under a fixed-ratio 15 schedule of food delivery. Cumulative doses of nalbuphine produced nalbuphine lever responding at doses of 1.0 to 10 mg/kg and rate-suppressing effects at doses of 3.2 to 32 mg/kg. Experiments to evaluate the contribution of opioid receptor activity suggested that the stimulus effects of nalbuphine were mediated through mu systems, inasmuch as mu agonists (etorphine, fentanyl, morphine, buprenorphine, GPA 1657 and nalorphine) produced nalbuphine lever responding, whereas kappa agonists [EKC and U-50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl] benzeneacetamide methanesulfonate hydrate)] and nonopioids (d-pentazocine, d-amphetamine and ketamine) produced saline lever responding. dl-Pentazocine produced nalbuphine lever responding in one-half the rats tested. Both high and low efficacy agonists produced nalbuphine lever responding, but the antagonist naltrexone produced predominantly saline lever responding. Increasing the training dose of nalbuphine by a 0.50 log unit failed to alter the potency of nalbuphine or any other compound to produce nalbuphine lever responding, suggesting that these training doses produce a maximum amount of stimulation at the mu receptor. Naltrexone antagonized the discriminative stimulus but not the rate-decreasing effects of nalbuphine, suggesting that only the discriminative stimulus effects of nalbuphine are mediated by a mu opioid mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed1999

Nalbuphine hydrochloride dependence in anabolic steroid users.

Nalbuphine hydrochloride, a nonscheduled opioid agonist/antagonist analgesic, is currently approved for the treatment of pain. Recently, nalbuphine dependence was reported in three anabolic steroid users in Britain. To further document this phenomenon, we conducted interviews on eleven subjects who reported nalbuphine use. Eight subjects were clinically dependent on nalbuphine, and seven of the subjects who were asked about tolerance and withdrawal with nalbuphine acknowledged these symptoms. Eight subjects, who had never used drugs intravenously before, reported using nalbuphine by this route. Nalbuphine-related morbidity was extensive and included medical complications and psychiatric symptoms. Nalbuphine users also exhibited a high rate of comorbid Axis I disorders, including other substance misuse. Virtually all subjects described widespread nalbuphine use in the gymnasiums they frequented. These observations, together with the recent increase in nalbuphine-related articles in the lay press, suggest that nalbuphine may represent a new drug of abuse among athletes, especially those using anabolic steroids, and that nalbuphine's scheduling status may need to be re-evaluated.

Adult↗

PubMedDate not supplied

Increased naloxone potency induced by pretreatment with morphine and nalbuphine in mice.

Both morphine and nalbuphine were effective in suppressing the abdominal constriction response induced by intraperitoneal injection of acetic acid in mice. On a weight to weight basis, nalbuphine was more potent than morphine in this test. However, the effect of nalbuphine was more effectively blocked by naloxone. Pretreatment with morphine 2.0 mg/kg subcutaneously did not alter the antinociceptive effect of either morphine or nalbuphine measured 3 h later. However, naloxone was about 1.4-fold more effective in antagonizing the antinociceptive effect of both drugs in morphine-pretreated mice than in saline-pretreated animals. Pretreatment with nalbuphine (1.0-2.0 mg/kg s.c.) did not alter the antinociceptive effect of either morphine or nalbuphine measured 3 h later, while naloxone effect was more effective in antagonizing the antinociceptive actions of morphine and nalbuphine. The increases in naloxone potency in antagonizing morphine after nalbuphine pretreatment were not dose-dependent on the amount of nalbuphine in the pretreatment and they were only marginally significant. In addition, these increases were much lower than that induced by morphine pretreatment. On the other hand, the naloxone effectiveness against nalbuphine itself was enhanced to a greater extent than that induced by morphine pretreatment. Furthermore, these increases in naloxone potency showed a dose-dependent relationship to the amount of nalbuphine used in the pretreatment. Based on these results, it was concluded that nalbuphine is an analgesic drug with properties in between those of the full agonist morphine and the partial agonist pentazocine.

Abdomen↗

PubMed1988

Nalbuphine: an autoradiographic opioid receptor binding profile in the central nervous system of an agonist/antagonist analgesic.

Nalbuphine is a potent agonist/antagonist analgesic with a low side effect profile and low abuse potential. Previous studies have shown that nalbuphine produces predominantly agonist (analgesic) effects at kappa receptors and antagonist (morphine-reversal) effects at mu receptors in vivo. The present study was designed to localize the sites of nalbuphine binding to mu, delta and kappa opioid receptors in the central nervous system (CNS) using in vitro labeling light microscopic autoradiography. Mu, delta and kappa opioid receptors were labeled selectively using [3H]dihydromorphine, D-[3H]Ala2-D-Leu5-enkephalin and (-)-[3H]ethylketocyclazocine, respectively. In displacement studies in rat brain homogenates, nalbuphine had the highest affinity (Ki) for mu receptors (0.5 nM) with progressively lower affinities for kappa (29 nM) and delta (60 nM) opioid receptors. In autoradiographic studies in slide-mounted sections of guinea pig brain and monkey spinal cord, nalbuphine (300 nM) displaced completely the binding at mu and kappa receptors without significantly altering the binding at delta receptors. The binding of [3H]nalbuphine in slide-mounted sections of guinea pig forebrain was saturable and showed a curvilinear profile indicating the presence of two binding sites with apparent dissociation constant (Kd) values of 0.5 and 12 nM. Morphine and U-50,488H, which have high affinities for mu and kappa opioid receptors, respectively, inhibited [3H]nalbuphine binding with IC50 values of 0.9 and 10 nM, respectively. In saturation studies, morphine (50 nM) and U-50,488H (100 nM) selectively blocked the high and low affinity components of [3H]nalbuphine binding, respectively. The autoradiographic distribution of [3H]nalbuphine binding sites in the CNS corresponds well to the distribution of mu and kappa opioid receptors. In addition, CNS areas (deep layers of the cerebral cortex, laminae I and II of the spinal cord, substantia gelatinosa of the trigeminal nerve, periaqueductal gray and thalamic nuclei) that mediate analgesia contain high concentrations of [3H]nalbuphine binding sites. In summary, these data demonstrate that nalbuphine acts on mu and kappa opioid receptors and identify anatomical loci in the CNS in which nalbuphine may produce its actions.

Analgesia↗

PubMed1994

Antinociceptive and respiratory effects of nalbuphine in rhesus monkeys.

Antinociceptive and respiratory effects of nalbuphine and other opioids were studied in rhesus monkeys. In a thermal, tail withdrawal assay, the kappa agonist enadoline and the mu agonists alfentanil and fentanyl produced maximum antinociceptive effects in all subjects and over a wide range of temperatures, whereas nalbuphine produced antinociceptive effects in only some subjects and only when the water temperature was < or = 50 degrees C. Naltrexone antagonized the antinociceptive effects of nalbuphine, alfentanil and enadoline; however, the magnitude of antagonism was not equal among agonists. In subjects that did not show an antinociceptive response to nalbuphine, nalbuphine (3.2-10.0 mg/kg) antagonized the antinociceptive effects of fentanyl but not enadoline. The irreversible opioid antagonist clocinnamox produced a parallel shift to the right in the nalbuphine dose-effect curve 1 hr after administration and decreased the maximum effect produced by nalbuphine 24 and 48 hr after administration. Nalbuphine had modest respiratory-depressant effects in monkeys breathing air and attenuated hyperventilation produced by 5% CO2. In contrast, alfentanil had marked respiratory-depressant effects in monkeys breathing air or 5% CO2 in air and these effects were antagonized by nalbuphine. Taken together, these results suggest nalbuphine has low efficacy at mu opioid receptors; however, quantitative differences between alfentanil and nalbuphine indicate a second (non-enadoline sensitive) receptor might also be important for the antinociceptive effects of nalbuphine.

Alfentanil↗

PubMed1996

Discriminative stimulus effects of nalbuphine in rhesus monkeys.

Three rhesus monkeys discriminated between 0.178 mg/kg of nalbuphine and saline while responding under a fixed-ratio 5 schedule of stimulus-shock termination. Nalbuphine produced dose-related increases in drug-lever responding with > or = 90% of responses occurring on the drug lever at doses larger than 0.1 mg/kg. The duration of action of the discriminative stimulus effects of nalbuphine was less than 5.25 hr. Rank order potency of compounds that substituted for the nalbuphine discriminative stimulus (i.e., > or = 90% responding on the nalbuphine lever) in all three subjects was fentanyl > butorphanol > methadone > morphine. Compounds that did not substitute completely in all monkeys included the kappa agonists ethylketocyclazocine, enadoline, spiradoline and U-50,488 and the nonopioids cocaine, d-amphetamine, clonidine, ketamine and phencyclidine. Naltrexone antagonized the discriminative stimulus effects of nalbuphine, shifting the nalbuphine dose-effect curve in a manner that was consistent with mu receptor mediation. Results from the current study demonstrate that, in rhesus monkeys, the discriminative stimulus effects of nalbuphine are mediated by mu opioid receptors. Although there is evidence suggesting that nalbuphine has kappa agonist effects (e.g., subjective effects in humans), results from several studies, including the current study, strongly suggest that in rhesus monkeys nalbuphine does not exert agonist actions at kappa receptors. Moreover, these data indicate that differences in behavioral effects between nalbuphine and prototypic mu opioids (e.g., morphine) probably result from differences in activity (e.g., efficacy) at mu receptors rather than any kappa agonist actions of nalbuphine.

Analgesics, Opioid↗

PubMed1997

Comparing the subjective, psychomotor and physiological effects of intravenous nalbuphine and morphine in healthy volunteers.

The purposes of this study were to characterize the subjective, psychomotor and physiological effects of nalbuphine in healthy non-drug abusing volunteers and to compare and contrast the effects of equianalgesic doses of nalbuphine and morphine. Subjects (12 males, 4 females) without histories of opiate dependence were injected in an upper extremity vein with 0, 2.5, 5.0 or 10 mg/70 kg nalbuphine, or with 10 mg/70 kg morphine, using a randomized, double-blind, crossover design. The 10-mg doses of nalbuphine and morphine are considered equianalgesic and are doses commonly given for relief of postoperative pain. Subjective effects of nalbuphine included increased scores on the Pentobarbital-Chlorpromazine-Alcohol Group scale and the Lysergic Acid Diethylamide scale of the Addiction Research Center Inventory; increased adjective checklist ratings of "nodding," "numb" and "sweating"; increased visual analog scale ratings of "coasting or spaced out," "high" and "sleepy" and increased "feel drug effect" and drug-liking ratings. Ten milligrams of nalbuphine had subjective effects similar, and similar in magnitude, to those of 10 mg of morphine. Nalbuphine produced exophoria and impairment on the Digit Symbol Substitution Test in a dose-related fashion. Ten milligrams of morphine produced exophoria but did not affect performance on the Digit Symbol Substitution Test. Both nalbuphine and morphine induced miosis and decreases in respiration rate. The results of the present study demonstrate that 2.5 to 10 mg nalbuphine had orderly, dose-related effects on subjective, psychomotor and physiological variables. The results also indicate that 10 mg of nalbuphine produces a profile of subjective, psychomotor and physiological effects similar to that of an equianalgesic dose of morphine (10 mg). The similarity in profiles between drugs at this dose is consistent with both infrahuman studies, which suggests that nalbuphine is a mu agonist, and studies with nondependent opioid abusers, in which relatively low doses of nalbuphine (such as 10 mg) produce morphine-like effects.

Adult↗

PubMedDate not supplied

Determination of nalbuphine in drug abusers' urine.

Nalbuphine, chemically derived from the oxymorphone, is a potent analgesic with narcotic antagonist activity. Because of the limited availability of methamphetamine, the abuse of nalbuphine as an alternative for methamphetamine began in late 1991 in Korea. In this study, the analysis of nalbuphine by gas chromatography (GC) was investigated. Using solid-phase extraction, we analyzed drug abusers' urine samples in order to quantitate nalbuphine by GC after trimethylsilyl derivatization with N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA), trimethylsilylimidazole (TSIM), and 1% trimethylchlorosilane (TMCS) (100:2:5). Nalbuphine and its two metabolites, nornalbuphine and 6-ketonalbuphine, were identified by gas chromatography-mass spectrometry. The ratio of total (i.e., nonconjugated and glucuronide) nalbuphine to nonconjugated nalbuphine ranged from 1.8 to 3.0 in the five drug abusers' urine. The urinary excretion of nalbuphine showed that 93% of nalbuphine was excreted in 6 h after intraperitoneal administration of 10 mg/kg nalbuphine to five rats. No nalbuphine was detected in the urine specimens of rats from 24 to 48 h.

Animals↗

PubMed1989

A study of the analgesic interaction between intrathecal morphine and subcutaneous nalbuphine in the rat.

Nalbuphine reverses opioid-induced respiratory depression, but the effect on analgesia is unclear. The analgesic interaction between subcutaneous (sc) nalbuphine and intrathecal morphine in conscious, male, Sprague-Dawley rats implanted with chronic intrathecal catheters was investigated. Nalbuphine (10 mg/kg) injected 30 min after intrathecal morphine (4 micrograms) significantly antagonized the effect of morphine in the tail flick test. The antagonism was rapid in onset and persisted beyond the experimental period of 240 min. The magnitude and the duration of the effect were comparable to that observed with sc naloxone (1 mg/kg). In contrast to the results in the tail flick test, nalbuphine enhanced the effect of intrathecal morphine in the noninflamed paw pressure test. Nalbuphine (10 mg/kg) alone had no effect on the time course of tail flick latency but significantly increased paw pressure threshold during the 15-90 min interval after sc injection. Nalbuphine (0.5 mg/kg, sc) alone had no antinociceptive effect in either pain test and did not antagonize the antinociceptive effect of intrathecal morphine (4 micrograms) in the tail flick test. However, sc nalbuphine (0.5 mg/kg), injected 30 min after intrathecal morphine (1.5 micrograms), significantly enhanced the effect of morphine in the paw pressure test compared with intrathecal morphine + sc saline-treated rats. The results indicate a complex analgesic interaction between intrathecal morphine and sc nalbuphine. The net analgesic effect during the interaction was determined by the following: 1) the doses of morphine and nalbuphine; 2) the time after nalbuphine administration; and 3) the nature of the nociceptive stimulus. At lower doses, sc nalbuphine appeared to potentiate the effect of intrathecal morphine in the noninflamed paw pressure test.

Analgesics↗

PubMed2004

Effects of opioids in morphine-treated pigeons trained to discriminate among morphine, the low-efficacy agonist nalbuphine, and saline.

In opioid-dependent subjects, the low-efficacy mu agonist nalbuphine generally precipitates withdrawal or withdrawal-like stimulus effects. To provide a more complete characterization of the discriminative stimulus effects of nalbuphine in opioid-treated subjects, seven White Carneux pigeons were treated daily with 10 mg/kg morphine i.m. and trained 6 h later to discriminate among 10 mg/kg morphine, 1.0 mg/kg nalbuphine, and saline by responding on one of three different keys. When tested, morphine produced morphine-key responding and nalbuphine produced nalbuphine-key responding. Replacing the daily morphine injection with saline produced nalbuphine-key responding, and this effect was reversed by the administration of morphine. In substitution tests with other compounds, the antagonists naltrexone (i.m.) and CTAP (D-Phe-Cys-Tyr-D-Tryp-Lys-Thr-Pen-Thr-NH2) (i.c.v.) produced nalbuphine-key responding. High-efficacy agonists fentanyl and etorphine produced morphine-key responding. The intermediate-efficacy agonists buprenorphine, dezocine, and butorphanol produced a pattern of morphine-, saline-, and/or nalbuphine-key responding that differed across individual pigeons. The lower efficacy agonists nalorphine and levallorphan produced predominantly nalbuphine-key responding. The kappa agonists spiradoline and U50,488 [trans-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]cyclohexyl)benzeneacetamide methanesulfonate], the nonopioid d-amphetamine, and saline produced predominantly saline-key responding. Naltrexone and nalbuphine dose dependently reversed the morphine-key responding produced by the training dose of morphine. Together, these data suggest that the discriminative-stimulus effects of the low-efficacy micro agonist nalbuphine in morphine-treated pigeons are similar to those of other low-efficacy agonists, naltrexone, and the termination of daily morphine treatment.

Animals↗