Efficacy of Nalbuphine as a Local Anesthetic Adjuvant for Brachial Plexus Block: A Systematic Review and Meta-analysis.

BACKGROUND: Nalbuphine has been increasingly used as a local anesthetic adjuvant to extend the duration of analgesia in brachial plexus block (BPB). OBJECTIVES: To systematically and firstly evaluate the available evidence on the efficacy of nalbuphine as an adjuvant to local anesthetics in BPB. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Cochrane Central Register of Controlled Clinical Trials, Cochrane Database of Systematic Reviews, Medline, Embase, Scopus, Web of Science, EBSCO, PubMed, and additional databases were searched. Randomized controlled trials comparing combination of perineural nalbuphine with local anesthetics to local anesthetics alone in BPB for upper extremity surgical procedures were eligible for inclusion. RESULTS: Nineteen randomized controlled trials involving 1,355 patients met the inclusion criteria. Perineural use of nalbuphine prolonged the duration of analgesia in BPB (mean difference [MD], 162.5; 95% confidence interval [CI], 119.0 to 205.9; P < 0.00001; very low quality of evidence). The duration of sensory block was also extended (MD, 141.6; 95% CI, 100.3 to 182.9; P < 0.00001; very low quality of evidence). Furthermore, nalbuphine shortened the onset time of sensory block (MD, -2.6; 95% CI, -3.6 to -1.5; P < 0.00001; very low quality of evidence). There were no significant differences in side effect-related outcomes, including nausea (risk radio [RR], 1.56; 95% CI, 0.82 to 2.59; P = 0.17; moderate quality of evidence) and vomiting (RR, 1.41; 95%  CI, 0.66 to 3.02; P = 0.38; moderate quality of evidence). LIMITATIONS: The study was limited by substantial heterogeneity, a relatively small sample size and difference-in-differences in how outcomes of interest were described and assessed. CONCLUSIONS: Perineural use of nalbuphine in BPB is an effective strategy for analgesia in adult patients undergoing upper extremity surgery.

Neurotoxic effect of nalufin on the histology, ultrastructure, cell cycle and apoptosis of the developing chick embryo and its amelioration by selenium.

The use of opioids during pregnancy has recently dramatically increased presenting major health problems, especially on the developing neonatal nervous system development. Nalufin is considered one of the most used opioid analgesics for treatment of moderate to severe pain, especially during pregnancy. The aim of the present study was firstly to assess the possible neurotoxic effects of nalufin injection during the organogenesis period of chick embryos, and second to investigate the ameliorative effects of selenium as a supplement. Fertilized chicken eggs were in ovo injected with 0.2ml of either nalufin (20 mg/kg egg) or selenium (0.1 mg/kg egg) or both. Nalufin injection resulted in cerebral cortical layer disruption, increase of Caspase-3 immunoexpression and chromatolytic nuclei, degenerated organelles, rarefied cytoplasm and hemorrhage. On the molecular levels, nalufin induced DNA fragmentation, cell cycle arrest and increased the percentage of apoptosis of the neuronal cells. Selenium combined treatment restored the three-layered structure of the cerebral cortex, decreased caspase-3 immuno-expression, improved ultrastructure and recovered cell cycle arrest, decreased apoptosis, and DNA degradation. In conclusion, nalufin treatment during pregnancy imposes great concerns and should not be used during embryonic development, on the other hands, selenium appears to be a promising neuroprotective agent against nalufin-induced neurotoxicity.

Albizia anthelmintica: HPLC-MS/MS profiling and in vivo anti-inflammatory, pain killing and antipyretic activities of its leaf extract.

In the current work, the phytochemical composition of a leaf methanol extract from Albizia anthelmintica was thoroughly investigated. The antioxidant, anti-inflammatory, analgesic, and antipyretic activities of the extract were investigated. In the carrageenan induced hind paw edema bioassay; the extract significantly reduced the edema thickness in rats and diminished the leukocyte migration to the peritoneal cavity in mice. The extract exhibited central and peripheral anti-nociceptive effects; it significantly decreased the number of acetic acid induced writhes and prolonged the latency time in the hot plate test. The extract showed a substantial antipyretic activity as it decreased significantly the elevated rectal temperature in mice after intraperitoneal injection of Brewer's yeast. Molecular docking of some major compounds in the extract to COX-1, COX-2 and 5-LOX, enzymes involved in the inflammation cascade, revealed appreciable interactions with the conserved amino acid residues in these target proteins. These findings were confirmed with in vitro enzyme inhibitory assays in which the extract showed IC50 values of 4.11, 0.054, and 1.74 µg/mL towards COX-1, COX-2 and 5-LOX, respectively. The extract displayed solid antioxidant properties as well with a TAC value of 35.13 U/L and EC50of 5.36 µg/mL in DPPH assay. These findings suggested that Albizia anthelmintica is a good antioxidant with potential therapeutic efficacy for treating inflammation, pain and related oxidative stress disorders.

End-Stage Renal Disease Chronic Itch and Its Management.

End-stage renal disease chronic itch is a frequent symptom that bothers patients with advanced stages of chronic kidney disease. The pathogenesis of the chronic itch symptom is complex and not yet fully understood and includes many metabolic, immunologic, and neurogenic factors. A significant burden of the disease results in decreased quality of life with sleep impairment, depressive symptoms, and increased mortality of affected individuals. No treatment of choice is available; topical therapy (emollients), phototherapy (UV-B), and systemic therapy (antiepileptics, opioid agonists, and antagonists) provide significant relief in varying percentages of patients.

Anti-nociceptive and anti-inflammatory activities of Wrightia arborea.

Anti-nociceptive and anti-inflammatory effects of methanolic extract of Wrightia arborea (MEWA) were examined using different models in rats. MEWA was given to rats orally upto 2000 mg kg(-1) b.wt. for acute toxicity study and observed for 14 days. Anti-nociceptive activity was evaluated in rats against Acetic acid induced writhing (chemically induced pain) and Tail immersion method (thermally induced pain). Acute anti-inflammatory activity of MEWA was also evaluated in Formaline-induced rat paw edema model and Carrageenan-induced hind paw edema model in rats. Results demonstrated that no mortality was found upto single dose of 2000 mg kg(-1) b.wt. in rats even after 14 days observation. In comparison to control group MEWA at 100 and 200 mg kg(-1) b.wt. showed highly significant anti-nociceptive activity against chemically (p < 0.001) as well as thermally (p < 0.05 and p < 0.001) induced pain as compared to standard drugs, indomethacin and nalbufin, respectively. In the formalin test, both the doses of 100 and 200 mg kg(-1) of extract significantly prevented increase in volume of paw edema (p < 0.05 and p < 0.01) both in the neurogenic and inflammatory phases. MEWA (200 and 400 mg kg(-1) p.o.) also significantly prevented increase in volume of paw edema in Carrageenan test (p < 0.05 and p < 0.001). The results suggest that MEWA has significant analgesic and anti-inflammatory potential which may be mediated by central and peripheral mechanism.

Strabismus surgery under augmented topical anesthesia.

PURPOSE: Recently, topical lidocaine 2% jelly had been used in phacoemulsification and trabeculectomy surgeries. The purpose of this study is to evaluate the efficacy and stability of one-stage adjustable suture using topical lidocaine jelly 2% in combination with intravenous nalbuphine (Nubain). METHODS: Forty adult patients aged 16 to 46 years (median, 24 years) underwent adjustable rectus muscle surgery under topical lidocaine jelly 2% and intravenous 10 mg nalbuphine given 10 minutes before surgery. Adjustment was performed on the operating table before conjunctival closure. The stability of adjustment was studied by comparing the postadjustment deviation to that at 1 day, 1 week, and 3 weeks postoperatively. Success was defined as alignment within 10 prism diopters on distant fixation. Analgesia was assessed using Verbal Description Scale. Changes in vital signs were recorded during surgery to evaluate the oculocardiac reflex. RESULTS: Forty rectus muscles were recessed, 22 muscles were resected, 3 muscles were tucked, and 2 muscles were retrieved. During the operation, 35 patients expressed no pain, 3 patients complained of discomfort, and 2 patients complained of distressing pain and required an additional 10 mg of intravenous nalbuphine. Thirty-eight patients (95%) were successfully aligned during the first postoperative day, 37 patients (92.5%) after 1 week, and 36 patients (90%) after 3 weeks. Intraoperative cardiac monitoring did not record positive oculocardiac reflex in any patient. CONCLUSION: Lidocaine jelly in combination with intravenous nalbuphine is an effective topical anesthesia strategy that provides for the patient's comfort and the surgeon's ability to fine-tune ocular alignment on the operating table.

In vitro and in vivo evaluation of the metabolism and pharmacokinetics of sebacoyl dinalbuphine.

A diester prodrug of nalbuphine, sebacoyl dinalbuphine (SDN), and its long-acting formulation are currently being developed to prolong the duration of nalbuphine. A comparative in vitro hydrolysis study was conducted for SDN in rat, rabbit, dog, and human blood. Both SDN and nalbuphine in blood or plasma were measured by high-performance liquid chromatography. The hydrolysis rates of SDN in blood were ranked as follows: rat > rabbit > human > dog. The rapid formation of nalbuphine in the blood accounted for almost 100% of the prodrug, which supported the contention that nalbuphine is the major metabolite after SDN hydrolysis. The hydrolysis profiles of SDN were similar both in plasma and in red blood cells when compared in the blood. In vitro release results of SDN long-acting formulation showed that the rate-limited step of SDN hydrolysis to nalbuphine in blood is the penetration of SDN from oil into the blood. After intravenous administration of SDN in sesame oil into rats, nalbuphine quickly appeared in plasma and, thereafter, exhibited monoexponential decay. Pharmaceutical dosage forms affecting the drug disposition kinetics were demonstrated after intravenous administration. The AUC of nalbuphine was significantly higher and clearance was significantly lower, without changes in the t(1/2) of nalbuphine after intravenous dosing of SDN in sesame oil when compared with that of intravenous dosing with nalbuphine HCl in rats. Overall, these results suggest that SDN fulfilled the original pro-soft drug design in which the prodrug can rapidly metabolize to nalbuphine, and no other unexpected compounds were apparent in the blood.

Comparison of Midazolam with and without Nalbuphine for Intravenous Sedation in Nasal Surgery / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Effective and safe premedication in nasal surgery is very important in nasal surgery under local anesthesia. We investigated the effects of preoperative administration of midazolam only and midazolam combined with nalbuphine HCl for nasal surgery under local anesthesia. SUBJECTS AND METHOD: A total of 30 patients presenting for nasal surgery under local anesthesia were randomly assigned. Patients in the midazolam group (n=15) received single administration of midazolam and subjects in the nalbuphine group (n=15) were injected nalbuphine in addition to midazolam. Cardiovascular and respiratory status were monitored continuously. Questionnaires were given to the operator and the patients, and the scores were compared statistically. RESULTS: Operator's assessment indicated better pain control gain in the nalbuphine group. The other parameters in the operator's assessment and the patient's assessments were not statistically significant between the two groups. No adverse cardiovascular and respiratory side effects were noted, but pruritus was observed more frequently in the nalbuphine group. CONCLUSION: Better pain control gain was indicated only by the surgeon for the nalbuphine group, but there was no additional advantage in other parameters of combining nalbuphine with midazolam. We concluded that a single preoperative administration of midazolam would be effective enough and serve as a safe method for simple nasal surgery.

Antinociceptive effect of a novel long-acting nalbuphine preparation.

BACKGROUND: A long-acting analgesic may be particularly desirable in patients suffering from long-lasting pain. The aim of the study was to evaluate the antinociceptive effect of a novel nalbuphine preparation and to determine its duration of action. METHODS: The antinociceptive effects of i.m. nalbuphine HCl in saline and nalbuphine base in sesame oil were evaluated in rats. The in vitro drug-releasing profiles of nalbuphine HCl and base in different preparations were also evaluated. RESULTS: We found that i.m. nalbuphine HCl 25, 50 and 100 micromol kg(-1) produced dose-related antinociceptive effects with a duration of action of 1.5, 2 and 3 h, respectively. i.m. nalbuphine base 100, 200 and 400 micromol kg(-1) also produced dose-related antinociceptive effects but with longer durations of action: 27, 49 and 55 h, respectively. In vitro studies demonstrated that nalbuphine base in sesame oil had the slowest drug-releasing profile of the different preparations. CONCLUSIONS: i.m. injection of an oil formulation of nalbuphine base produced a long-lasting antinociceptive effect.

Nalbuphine by PCA-pump for analgesia following hysterectomy: bolus application versus continuous infusion with bolus application.

The analgesic properties of the partial agonist-antagonist nalbuphine in the postoperative period are well known. When used for patient-controlled analgesia (PCA) the effectiveness of this substance is comparable to that of morphine or tramadol. However, the optimal programme for administration of nalbuphine in PCA-pumps has not been investigated. In particular, the combination of bolus administration vs bolus administration plus continuous basal administration is disputable. We hypothesized that the administration of an extra basal rate of nalbuphine in addition to the patient- triggered bolus administration and supplemental doses of diclofenac when required, would lead to a significant improvement in analgesia, without affecting the differences in vital signs and side effects. After approvement by the institutional ethics committee, 50 female patients (ASA I or II) scheduled for elective hysterectomy were included in a prospective, single-blinded study and randomized either into bolus-continuous (BC-)group (3 mg base rate/h, 1 mg bolus, 20 min lock out) or bolus (B-)group (no base rate, 1 mg bolus, 10 min lock out). During the observation period (up to 24 h postoperative) vital parameters, extent of analgesia (10-step VAS), and vigilance (5-step scale) were registered. Groups were compared by using unpaired Student t-test. A p<0.05 was considered to be significant. No differences were found in demographic data or vital parameters (MAP, PaO2, PaCO2, respiratory rate, heart rate, peripheral SaO2) during the observation period. Vital parameters showed no pathological changes in any group. With an identical rate of requirement for diclofenac (32 and 36%), analgesia in BC-group showed a decrease in VAS from 4.28+/-2.11 to 2.04+/-1.21 and from 3.64+/-2.20 to 2.08+/-0.96 in B-group. Vigilance was only marginally diminished in both groups. No serious side effects were found in either group. The consumption of nalbuphine (mg) was significantly higher in BC-group (70.28+/-13.85 vs. 47.44+/-22.99;p =0.0002) when compared to B-group. Subjective rating of effectiveness by the patients was similar in both groups. The two administration settings of nalbuphine by PCA pump have shown to be equally effective in the treatment of postoperative pain following hysterectomy. However, as the total amount of nalbuphine was significantly lower in B-group, the use of this administration schedule should be encouraged.

Comparación entre la nalbufina y la meperidina para el tratamiento del escalofrío posanestésico / Comparation between nalbuphine and the meperidime for the postanesthetics shinering treatment

El propósito del siguiente estudio es demostrar que la nalbufina es una alternativa para el tratamiento de los escalofríos posanestésicos. El escalofrío posanestésico es desagradable para el paciente pudiendo producir variedad de complicaciones. En este estudio doble ciego, aleatorio, se evaluó la nalbufina comparándola con la meperidina para el tratamiento del escalofrío. Cuarenta pacientes adultos fueron incluidos en este trabajo. El grupo 1 recibió nalbufina 0,08 mg/kg vía endovenosa y el grupo 2 meperidina 0,4 mg/kg. El tratamiento que elimina los escalofríos era considerado exitoso pero los resultados demostraron que 5 minutos después del tratamiento ambas drogas proveen un rápido y potente efecto antiescalofríos. La respuesta efectiva fue de 95 por ciento y 90 por ciento, para meperidina y nalbufina respectivamente; treinta minutos después la respuesta fue de 100 por ciento de efectividad para ambas. La diferencia entre la nalbufina y meperidina no fue significativa (p<0,05). Concluimos que la nalbufina puede ser una alternativa a la meperidina para el escalofrío pasanestésico

[Peribulbar anesthesia for peroperative and postoperative pain control in eye enucleation or evisceration: 31 cases]. / L'anesthésie péribulbaire pour le contrôle de la douleur per et postopératoire au cours des énucléations ou éviscérations. Trente et un cas.

OBJECTIVES: The aim of this prospective study was to assess peroperative and postoperative analgesia in eye enucleation or evisceration performed under peribulbar anesthesia. PATIENTS AND METHODS: We report 31 patients undergoing an eye enucleation (17 cases) or evisceration (14 cases). The surgical procedure was performed under local anesthesia alone in 22 patients. General anesthesia was associated with local anesthesia in 9 patients. Peribulbar block was achieved with the first insertion of the needle parallel to the inferior orbital floor and the second at level of supraorbital notch. A mixed anesthetic solution of equal quantity of lidocaine 2% with epinephrine (0.25 mg/20 ml) and bupivacaine 0.50% with epinephrine (0.10 mg/20 ml) was injected (total quantity 16.8 +/- 4.3 ml). RESULTS: To assess the peroperative pain we considered the patients with local anesthesia only (22 patients). One of these 22 patients needed one injection (0.50 mg/kg) of propofol for cutting the optic nerve. Surgery was ended without any other drug but that case was considered as a failure. Peroperative analgesia was obtained in 21 of 22 patients (95.4%). To assess analgesia in the postoperative period we included 31 patients. Analgesia was complete from the accomplishment of the peribulbar block to the 4th hour in all patients (efficacy 100%). From the 4th to the 24th hour, pain remained absent in 11 (enucleation 10 cases and evisceration 1 case) of the 31 patients and no drug was used. In 20 patients (enucleation 7 cases and evisceration 13 cases), pain appeared between the 4th and the 10th hour and patients were relieved by paracetamol alone in 14 cases (enucleation 6 cases and evisceration 8 cases) or by its association with nalbuphine in 5 cases (enucleation 1 case and evisceration 4 cases). In one patient (evisceration) the association of the drugs was uneffective. CONCLUSION: Peribulbar anesthesia is safe and generates major postoperative analgesia so we suggest to offer that technique to patients undergoing evisceration or enucleation.

Clinical Experience of PhysioFlex Anesthesia Machine / 대한마취과학회지

BACKGROUND: The anesthesia machine PhysioFlex was especially constructed to deliver anesthetics in a closed circuit system. In this anesthesia machine the concentrations of the respiratory gases and the gas volume in the circle system are automatically controlled by a feedback mechanism. The aim of this study is to introduce 1,132 patients who have received general anesthesia in a closed circuit system using PhysioFlex, and to calculate the real consumed amount of oxygen and nitrous oxide, and to describe the advantages and disadvantages of PhysioFlex for clinical uses. METHOD: The author used a PhysioFlex in cases of 1,132 various surgical interventions. After induction with thiopentone and suxamethonium, general anesthesia was maintained with nitrous oxide in 50% oxygen and enflurane (or isoflurane, halothane) and supplemented with nalbuphine and pancuronium. These cases were analyzed by their sex, age, height, weight, method of airway maintenance during general anesthesia, operation position, anesthesia time, and arterial blood gases by review of anesthesia records. Average minute-consumed amount of oxygen and nitrous oxide was calculated by recording every 30 seconds throughout the anesthesia procedures except preoxygenation and flush periods. The advantages and disadvantages of PhysioFlex were described on the base of the author's clinical experience. RESULTS: The anesthetic technique of the closed circuit system by PhysioFlex could be used adequately for any surgical procedures. In this system consumed amounts of oxygen and nitrous oxide were 179.72+/-2.48 ml/min and 88.49+/-2.78 ml/min respectively. The author found out several advantages and few disadvantages of PhysioFlex for its clinical uses. CONCLUSIONS: Closed circuit system of PhysioFlex anesthesia machine offer numerous advantages such as reduction of gas consumption, low cost, less pollution in both the operating theater and the environment, increase in inspired gas humidity, easy handling of machine, and excellent respiratory alarm systems.

Effects of Succinylcholine on the Recovery of Vecuronium-induced Neuromuscular Block / 대한마취과학회지

BACKGROUND: Succinylcholine is commonly used for tracheal intubation during induction of anesthesia and followed by a nondepolarizing neuromuscular blocking drug for intraoperative muscle relaxation. We have determined whether the effect of succinylcholine used for endotracheal intubation on the recovery of vecuronium-induced neuromuscular block offers many changes in time course of neuromuscular block. METHOD: Forty ASA class 1 or 2 adult male patients were studied. Patients were premedicated with nalbuphine 10 mg and glycopyrrolate 0.2 mg and after induction of anesthesia with thiopental, anesthesia was maintained with 1~2% enflurane, and 50% nitrous oxide in oxygen. Twitch responses of adductor pollicis were measured acceleromyographically using 0.2 ms, 2 Hz, train of four (TOF) stimulation of ulnar nerve every 15 seconds. The patients were allocated randomly to following four groups; Ten patients received vecuronium 0.1 mg/kg only (group 1), remained thirty patients received succinylcholine 1.0 mg/kg first and vecuronium 0.1 mg/kg was administered at 0% (group 2, n=10), 25% (group 3, n=10), 75% (group 4, n=10) recovery of first twitch from succinylcholine-induced neuromuscular block respectively. RESULT: Clinical duration, recovery index, and TOF ratio of vecuronium were not significantly different between groups. CONCLUSION: Succinylcholine for endotracheal intubation during induction of anesthesia does not affect time course of action of vecuronium-induced neuromuscular block. The cause of this result suspect that the effect of succinylcholine might be masked by large dose of vecuronium (2XED95). Clinically, it is unlikely that prior administered succinylcholine 1 mg/kg influence the recovery of vecuronium-induced neuromuscular block.

Analgesia interpleural / Interpleural analgesia

O autor em face de sua preliminar experiência pessoal com uma nova técnica de analgesia regional, com bons resultados faz uma revisäo bibliográfica crítica do assunto. Descreve a técnica usada, as indicaçöes, vantagens e complicaçöes. Coloca em discussäo as controvérsias existentes, como a terminologia mais correta, mecanismos de açäo, possível envolvimento da cadeia simpática torácica, melhor dose do A. L., adiçäo de adrenalina, distribuiçäo do A. L., e, ainda, outras possíveis indicaçöes, como, também, os potenciais efeitos adversos. A conclusäo enfatiza a necessidade de mais estudos para o benefício e segurança do paciente e, também, da anestesiologia moderna.

Effect of labor analgesia with nalbuphine hydrochloride on fetal response to vibroacoustic stimulation.

OBJECTIVE: To evaluate the effect of labor analgesia with nalbuphine hydrochloride on the fetal response to vibroacoustic stimulation. STUDY DESIGN: The response to fetal acoustic stimulation (FAS) was recorded in 27 laboring patients before analgesia. After analgesia with 5 mg nalbuphine hydrochloride administered subcutaneously, the response to FAS was again recorded. RESULTS: No ominous fetal heart rate (FHR) patterns were observed. FAS reliably increased FHR baseline and long-term FHR variability and produced FHR accelerations. Nalbuphine hydrochloride analgesia did not produce a significant decrease in long-term FHR variability or alter FHR baseline but did reduce the number of FHR accelerations recorded. CONCLUSION: FAS-induced FHR accelerations did not differ from those observed before analgesia. Analgesia with low doses of nalbuphine did not alter fetal response to FAS, which therefore offers a means of assessing fetal well-being even in the narcotized fetus.

Comparación entre la anestesia local y el bloqueo peridural en plastia inguinal / Comparison between local anesthesia and peridural block used in inguinoplasty

En este estudio se recomienda la anestesia local como procedimiento de elección en la reparación de la hernia inguinal unilateral y no complicada. Se presenta un estudio prospectivo, comparativo y aleatorio en 165 pacientes con hernia inguinal, dividiéndolos en dos grupos: grupo I, 80 pacientes operados con anestesia local; grupo II, 85 pacientes operados bajo bloqueo peridural. Se excluyeron los pacientes con hernia recidivante o complicada. El tiempo anestésico-quirúrgico empleado fue menor en el grupo I, con promedio de 71.5 minutos en comparación al II, que empleó 121.3 minutos en promedio. Las complicaciones fueron menores en el grupo I y la estancia hospitalaria fue significativamente menor en comparación al grupo II. Se considera que la anestesia local en la plastia inguinal unilateral y no complicada debe ser el procedimiento de elección por su buena tolerancia y efectividad, únicamente se requiere experiencia en su uso por parte del cirujano

Influence of ketamine and its interactions with morphine and nalbuphine on the level of enkephalins in some parts of the brain and spinal cord.

The aim of this paper was to study the influence of ketamine in a dose of 80 or 160 mg/kg ip on the level of leu-enkephalin (LENK) or met-enkephalin (MENK) in some parts of the brain and spinal cord, as well as to examine the interaction of ketamine with morphine or nalbuphine on this effect. The influence of ketamine on enkephalins release into the brain perfusate was also studied. Ketamine decreased the spinal cord enkephalins concentration mainly in cervical and lumbar part. These effect was antagonized by naloxone. Ketamine administered in a higher dose increased LENK release, and decreased the release of MENK into the brain perfusate. Morphine (20 mg/kg ip) increased the level of LENK in the hypothalamus, decreased the concentrations of MENK in the medulla oblongata and in the cervical part of the spinal cord, and increased the level of this neuropeptide in the thoracic part of the spinal cord. These effects were antagonized by ketamine. Ketamine and morphine administered simultaneously affected the level of enkephalins in some of the studied parts of the brain and spinal cord. Nalbuphine administered in doses ranging from 1 to 20 mg/kg changed the level of enkephalins in some parts of the central nervous system. Ketamine and nalbuphine administered simultaneously changed the level of enkephalins in the spinal cord and in the hypothalamus. It is concluded that: the decrease of the level of enkephalins in the spinal cord is an evident feature of ketamine action mediated probably by opioid receptors. Ketamine affects the release of LENK and MENK from the brain in a different way.(ABSTRACT TRUNCATED AT 250 WORDS)