Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study investigated the effect of a single, anesthetic dose of ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, on behavioral despair, an animal model of depression. Separate groups of male Wistar rats injected with an anesthetic dose of ketamine (160 mg/kg ip) and tested 3, 7, or 10 days later showed significantly less immobility in the second of two forced-swim tests compared to saline-injected controls. Ketamine- and saline-treated animals did not differ significantly in the swim tests with respect to other behavioral measures, namely diving, jumping, and head shakes. The present findings point to an ameliorative effect of ketamine on behavioral despair and support the view that NMDA antagonists may have a beneficial effect on depression.
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PMID:Prolonged effect of an anesthetic dose of ketamine on behavioral despair. 1181 42

The aim of this study was to elucidate the effects of midazolam and ketamine on neuromuscular blockade induced by non-depolarizing muscle relaxants (NDMRs) under the condition of sepsis induced by panperitonitis. A CLP operation (laparotomy, cecal ligation, and puncture of the cecum; septic group) or sham laparotomy (sham group) was performed on rats under O2-isoflurane anesthesia. At 18 hours after the operation, isometric twitch tensions of rat nerve-hemidiaphragm preparations elicited by indirect or direct stimulation at 0.1 Hz were measured. Midazolam enhanced the dTc (1 microM)-induced twitch depression (p < 0.05) at a high concentration (10 microM) in the septic group but not in the sham group. Ketamine enhanced the dTc (1 microM)-induced twitch depression in the sham group (p < 0.01) but not in the septic group. Midazolam and ketamine had no effect on directly elicited twitch tensions in either group. The results indicate that sepsis facilitates the midazolam-induced enhancement of the neuromuscular blocking effect of dTc but, conversely, inhibits the ketamine-induced enhancement. Sepsis elicits manifold alterations in the influence of intravenous anesthetics and sedatives on NDMR-induced neuromuscular blockade.
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PMID:The effects of midazolam and ketamine on D-tubocurarine-induced twitch depression in septic rat diaphragm. 1195 90

Owing to different mechanisms of analgesia, we hypothesized that the combination of ketamine and tramadol could produce synergistic or additive antinociceptive effects. Swiss albino mice were administered intraperitoneally with ketamine, tramadol, a combination of ketamine and tramadol, or saline, and the resulting antinociceptive effects were tested in the mouse tail-flick and formalin tests. The potencies of the two drugs alone or in combination were obtained by fitting data to the Sigmoid Emax equation. Isobolographic analysis was performed to evaluate the interaction. CNS depression was also monitored. Results showed that tramadol exhibited apparent dose-dependent effects in the tail-flick test, and in phase 1 and phase 2 of the formalin test. Ketamine dose-dependently inhibited the phase 2 responses, but failed to modify the phase 1 and tail-flick responses. Combination of tramadol and ketamine produced significant synergistic interactions only in phase 2 of the formalin test (P < 0.05). The synergistic combinations also displayed less CNS depression than when an equianalgesic dose of ketamine was administered alone. We conclude that in the acute thermal or chemical pain model, ketamine is not effective and the net effect of ketamine and tramadol in combination was simply additive after systemic administration. However, the coadministration produced synergistic antinociception in the chemical-induced persistent pain model.
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PMID:Isobolographic analysis of the analgesic interactions between ketamine and tramadol. 1200 57

Circadian rhythms impact many physiological functions that may affect drug pharmacological response. Ketamine is a dissociative agent commonly used for surgical anesthesia in rats. The aim of the present study was to analyze the central nervous system (CNS) depression and lethality of ketamine injected intraperitoneally at different times during the 24 h. The study was conducted in October 2001, spring in the Southern hemisphere. Female prepuberal Sprague-Dawley rats synchronized to a 12h light: 12h dark cycle (light, 07:00h-19:00h) were studied. Ketamine (40 mg/kg) was administered to one of six different clock-time treatment groups (n = 6-7 rats each). Duration of latency period, ataxia, loss of righting reflex (LRR), post-LRR ataxia, and total pharmacological response were determined by visual assessment. To investigate acute toxicity, ketamine lethal dose 50 (148.0 mg/kg) was also administered as a single injection to six different treatment-time groups of rats. Significant temporal differences and circadian rhythms were detected in drug-induced post-LRR ataxia and total pharmacological response duration. The longest pharmacological response occurred in rats injected during the light (rest) phase and the shortest response in the dark (activity) phase. No circadian rhythm was detected in acute toxicity. The study findings indicate that the duration of CNS depression of ketamine in rats exhibits circadian rhythmic variation.
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PMID:Treatment-time-dependent difference of ketamine pharmacological response and toxicity in rats. 1240 55

Epidural opioids have been reported to provide superior analgesia in acute pain management. Despite the fact that the required doses are low, major side effects such as respiratory depression may still occur. In an effort to maximize analgesia and to minimize the rate of side effects, epidural NMDA receptor antagonists, especially ketamine, may be co-administered with opioids. This study investigated whether ketamine had beneficial effects on fentanyl- or morphine-induced antinociception in an acute pain model in rats. In male Wistar rats, an epidural catheter was placed under general anaesthesia. After 1 week the animals were subjected to the tail withdrawal reaction (TWR) test. After determination of the basal reaction latencies, fentanyl, morphine, ketamine or combinations of an opioid with ketamine were administered epidurally. TWR latencies were measured for up to 2h after treatment. Both opioids showed a dose related antinociceptive effect. Fentanyl had a fast onset and a short duration of action whereas the reverse was true for morphine. Ketamine exhibited only limited antinociceptive properties. In the combinations, ketamine improved morphine-induced antinociception both in terms of maximal possible effect (MPE) as well as in duration of action. The combination of fentanyl with ketamine did not result in any improvement, neither in terms of MPE nor in duration of action. Moreover, increasing doses of ketamine tended to decrease the MPE of various doses of fentanyl. These data confirm that ketamine, contrary to opioids, does not possess important antinociceptive properties in an acute test such as the TWR test. Furthermore, these data indicate that additive drugs such as ketamine may have different effects on different opioids.
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PMID:Epidural ketamine potentiates epidural morphine but not fentanyl in acute nociception in rats. 1260 Jul 93

A 2.8-year-old female patient (11.6 kg) was admitted to the hospital for uncontrolled pain and swelling in the left leg relating to a metastatic neuroblastoma. Initially, her pain was managed with oral morphine 2 mg (approx. 0.2 mg/kg) every 4 hours. Because she was quite somnolent but still in significant pain, analgesia was then changed to methadone 1 mg orally every 6 hours (approximately 0.1 mg/kg/dose) and was eventually increased over 36 hours to 2 mg every 6 hours (approximately 0.2 mg/kg/dose). She received oral methadone 0.6 mg (approximately 0.05 mg/kg) every 4 hours as needed for breakthrough pain. She continued to have severe pain and experienced side effects, including respiratory depression, sedation, visual hallucinations, and vomiting. An intravenous ketamine infusion was started at 100 microg/kg/hour. Regular opioid administration was ceased, but she was given intravenous morphine 0.5 to 0.75 mg for breakthrough pain. She required only zero to three doses of breakthrough morphine per day, initially. After starting the ketamine infusion, her pain control improved and her symptoms of opioid toxicity abated. She was more alert and able to partake in limited activities. As a result of pain from progressive disease, the ketamine infusion was increased to 200 microg/kg/hour after 6 days with positive results. Her condition continued to deteriorate. An intravenous morphine infusion was initiated 2 weeks after starting the ketamine infusion and was eventually increased to 50 microg/kg/hour. One week later, she died with reasonable pain control. This case illustrates the use of ketamine as an effective analgesic in an adjuvant setting in a pediatric patient with advanced poorly controlled cancer pain. Ketamine not only eased the child's suffering while preserving life but also improved her quality of life by maintaining the child's ability to communicate and engage in activities.
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PMID:Intravenous ketamine infusion as an adjuvant to morphine in a 2-year-old with severe cancer pain from metastatic neuroblastoma. 1545 42

Ketamine is commonly administered in combination with benzodiazepines to achieve surgical anaesthesia in rats. The aim of the present study was to analyze the pharmacological response of the combination ketamine-midazolam injected intraperitoneally at different times of day to rats. The study was conducted in July 2003, during the winter in the Southern hemisphere. Female prepuberal Sprague-Dawley rats synchronized to a 12h light:12h dark cycle (light, 07:00-19:00h) were used as experimental animals. A combination treatment of ketamine (40 mg/kg) and midazolam (2 mg/kg) was administered to five different clock-time groups of rats (n=7/group). Duration of the latency period, ataxia, loss-of-righting reflex (LRR), post-LRR ataxia, and total pharmacological response were assessed by visual assessment. Significant treatment-time differences were detected in the duration of LRR, post-LRR ataxia, and total pharmacological response duration. The longest pharmacological response occurred in rats injected during the light (rest) phase, and the shortest pharmacological response occurred in rats injected during the dark (activity) phase. Cosinor analysis documented circadian rhythmicity in the duration of post-LRR ataxia. The findings of the study indicate the duration of CNS-depression of the ketamine-midazolam combination exhibits treatment-time-dependent variation in the rat.
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PMID:Chronobiological study of the pharmacological response of rats to combination ketamine-midazolam. 1547 Sep 56

The efficacy of ketamine and bupivacaine in enhancing the epidural analgesia induced by medetomidine was evaluated in 10 buffalo calves utilized repeatedly after a gap of 10 days so that each drug combination was tested in 4 randomly selected animals. In group A, medetomidine (15 microg/kg), in group B ketamine (2.0 mg/kg), in group C bupivacaine (0.125 mg/kg), in group D medetomidine and ketamine (15 microg/kg and 2.0 mg/kg), and in group E medetomidine and bupivacaine (15 microg/kg and 0.125 mg/kg) was administered epidurally. Onset of analgesia was significantly earlier in animals of groups B and D compared to the animals of groups A, C and E. Medetomidine alone or in combination with ketamine/bupivacaine produced complete analgesia of the tail, perineum, inguinal region and upper parts of hind limbs. Ketamine produced a very short duration of complete analgesia at the tail and perineum. Bupivacaine alone produced only mild to moderate analgesia. Both ketamine and bupivacaine prolonged the duration of analgesia. Motor incoordination was mild to moderate in animals of all the groups, but animals remained standing throughout the period of observation. Animals of groups A, D and E showed mild to moderate sedation during the observation period. Ruminal movements decreased nonsignificantly in animals of groups A and E. Mild salivation was observed in animals of all the groups except group C. Significant decrease in heart rate (HR) was recorded after epidural administration of medetomidine or bupivacaine; however, ketamine caused short duration of tachycardia. The administration of ketamine with medetomidine caused lesser decrease in HR compared to medetomidine alone or in combination with bupivacaine. Significant fall in respiratory rate (RR) was recorded after epidural administration of medetomidine or bupivacaine alone, but an increase in RR was recorded after ketamine administration. The fall in RR was less pronounced in animals in which medetomidine was used with ketamine compared to the animals in which medetomidine was used alone or in combination with bupivacaine. Mean arterial pressure (MAP) decreased and central venous pressure (CVP) increased significantly after epidural administration of medetomidine in combination with ketamine or bupivacaine. The ECG changes included tall T wave, QS pattern, RS pattern and ST elevation and heart blocks at different intervals, which were more frequent and pronounced in animals given bupivacaine with medetomidine. It can be concluded that epidural administration of medetomidine can produce complete analgesia of the tail, perineum, inguinal region and upper hind limbs in buffaloes. However, significant depression of cardiovascular parameters was recorded. Administration of ketamine along with medetomidine resulted in significantly early onset and slightly longer duration of analgesia with lesser cardiopulmonary side-effects compared to medetomidine alone or medetomidine with bupivacaine. Addition of ketamine to medetomidine thus seems to be useful for producing epidural analgesia; however, addition of bupivacaine failed to provide any advantage over medetomidine alone.
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PMID:Medetomidine with ketamine and bupivacaine for epidural analgesia in buffaloes. 1572 87

Ketamine is known to improve opioid efficacy, reduce postoperative opioid requirement and oppose opioid associated pain hypersensitivity and tolerance. However, the mechanisms underlying these beneficial effects are not clear. This study investigated the effects of ketamine at a non-analgesic dose (30 mg/kg, i.p.) on analgesia induced by morphine (2.5, 5.0, 7.5 mg/kg, s.c.), using rat tail-flick test as an animal model of acute pain. Further, the role of opioid-, alpha2-adrenoceptors and ATP-sensitive potassium channels was examined on the potentiating effect of ketamine. Male rats received morphine alone at 5.0 and 7.5 but not at 2.5 mg/kg showed a dose-related increase in tail-flick latencies. The combination of morphine and ketamine resulted in dose-related increase in morphine analgesia, both on the intensity as well as on duration. The ketamine-induced potentiation of morphine (7.5 mg/kg) analgesia was unaffected by glibenclamide (3 mg/kg, s.c.) and only partially blocked by yohimbine (2 mg/kg, i.p.), but more completely abolished by naloxone (2 mg/kg, i.p.). Both morphine (5.0 mg/kg) and ketamine (30 mg/kg) alone did not evoke catalepsy in rats but on combination produced a synergistic effect, which was however, abolished by naloxone pretreatment. In the open-field test, while morphine (5.0 mg/kg) caused a depressant effect, ketamine (30 mg/kg) enhanced the locomotor activity. Nevertheless, in combination potentiated the morphine's depressant effect on locomotion, which was also antagonized by naloxone. These results indicate that ketamine at a non-analgesic dose can potentiate morphine analgesia, induce catalepsy and cause locomotor depression, possibly involving an opioid mechanism. This potentiation, although favorable in acute pain management, may have some adverse clinical implications.
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PMID:Ketamine-induced potentiation of morphine analgesia in rat tail-flick test: role of opioid-, alpha2-adrenoceptors and ATP-sensitive potassium channels. 1639 16

Ketamine is believed to have sympathomimetic effects, although the central mechanism remains unclear. Using an in vitro splanchnic nerve-spinal cord preparation from neonatal rats, our previous investigations have demonstrated that tonic sympathetic activity is spontaneously generated from the thoracic spinal cord. We designed this study to investigate whether applications of ketamine to the cord would augment sympathetic activity and whether this action was dependent on N-methyl-d-aspartate receptors. Bath application of ketamine significantly reduced sympathetic activity in a concentration-dependent manner. Ketamine in 10, 20, 40, 80, and 120 microM reduced the sympathetic activity to 82.6% +/- 4.4% (P < 0.05), 61.7% +/- 5.1%, 42.8% +/- 4.2%, 24.9% +/- 4.4%, and 9.2% +/- 2.7% of the control value, respectively (P < 0.01, n = 8 for each test). The 50% inhibitory concentration of ketamine on sympathetic activity was 32 muM. Pretreatment with DL-2-amino-5-phosphonovaleric acid, a selective competitive N-methyl-d-aspartate receptor antagonist, did not alter ketamine-induced depression of sympathetic activity. These results suggest that ketamine reduces sympathetic activity by mechanisms that are independent of N-methyl-d-aspartate receptor activity.
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PMID:Ketamine attenuates sympathetic activity through mechanisms not mediated by N-methyl-D-aspartate receptors in the isolated spinal cord of neonatal rats. 1649 32


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