Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The electrical current thresholds for pain (ECTP) in the skin of the neck and tail were measured in rats with chronically implanted lumbar subarachnoid catheters. The effects of a benzodiazepine antagonist and a gamma-aminobutyric acid (GABA) antagonist on the analgesic effects of equivalent doses of midazolam, fentanyl, and ketocyclazocine were studied. These were the minimum doses producing maximal segmental analgesia when given intrathecally (i.e., they all caused a significant and maximum increase in ECTP in the tail, which was similar for all three drugs, but no significant change in the ECTP in the neck). Flumazenil (Ro 15-1788) administration caused a parallel shift to the right of the dose-response curve for midazolam spinal analgesia. Segmental analgesia following midazolam was also significantly attenuated (P less than 0.05) when the selective GABA antagonist bicuculline was given intrathecally at the same time as midazolam. The highest dose of bicuculline used (50 pmol) caused no significant attenuation of the segmental analgesic effects of either ketocyclazocine or fentanyl. The authors concluded that the segmental analgesia produced by intrathecal midazolam is mediated by the benzodiazepine-GABA receptor complex that is involved in other benzodiazepine actions.
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PMID:On the mechanism by which midazolam causes spinally mediated analgesia. 216 54

In 1988, the specific benzodiazepine antagonist, flumazenil (Anexate Roche), was introduced in clinical practice in Czechoslovakia for analgesia. A pilot study was initiated to establish whether .1 mg of flumazenil iv was capable of accelerating the psychic recovery of women after abortion. 30 healthy women aged 17-25 received a combination of .1 mg/kg-1 diazepam iv together with .88 mg/kg-1 ketamine iv. Another group of 10 women of the same age range were given .05 mg/kg-1 of midazolam iv. Flumazenil, in a dose of .1 mg iv, was administered to the women following the completion of the procedure, i.e., about 5-7 minutes after giving benzodiazepine. The effect of flumazenil became apparent 30 seconds after iv administration. The hypnotic-sedative effect of benzodiazepine set in after 30-60 seconds, and its biological half-life was 50-60 minutes. After administration of midazolam, an especially strong sedative effect was produced for operative intervention. The psychic effects of ketamine lasted only a little while and no occurrence of psychomimetic symptoms were observed as determined by an orientation test of place, time, and space. Retrograde amnesia was complete during the procedure. Partial amnesia occurred after administration of flumazenil. The lowest flumazenil doses antagonized only the hypnotic and sedative effects of benzodiazepine but did not influence the anxiolytic and amnestic effects. Systolic pressure increased by 10 torr: the pulse rate increased on the average from 74.4 - 84.8 beats/minute. Mild ataxia occurred in women who attempted to get out of bed, but 60 minutes after completion of the procedure, the patients were able to walk without ataxia. It was clearly demonstrated that the sedative-hypnotic effects of benzodiazepine can be subdued after abortion, shortening the period required for the recovery of the patient.
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PMID:[Initial experience with flumazenil (Anexate Roche) for abortion]. 250 17

In modern anaesthesia various antagonists are used. They provide efficient tools to facilitate better control of pharmacological effects and side effects of drugs routinely used in anaesthesia. Naloxone is a competitive antagonist of opioids without any intrinsic activity. It counteracts respiratory depression, pruritus, sedation and analgesia caused by opioids. It is fast-acting with a duration of action of 45 to 90 min. Several investigators have reported severe side effects of naloxone including hypertension, tachyarrhythmias, left heart failure and cardiac arrest, and hence the use of naloxone must be carefully considered in every single patient. Flumazenil is a competitive antagonist of benzodiazepines. It is a remarkably safe drug and very effective to terminate all benzodiazepine effects in anaesthesia and intensive-care patients. Serious complications caused by flumazenil have been reported in patients receiving benzodiazepines in the treatment of seizure disorders and in patients with mixed intoxications. Neostigmine is one of several antagonists of neuromuscular blocking agents. Its side effects include bradycardia, increased bronchial secretions and increased peristalsis. Indication depends on the results of neuromuscular monitoring. Physostigmine is an unspecific antagonist of the central anticholinergic syndrome, an acute psychosis that may be caused by numerous drugs used in anaesthesia. Generally, antagonists should be carefully titrated. In emergency medicine the use of these antagonists is not recommended; the primary goal is to restore vital functions.
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PMID:[Antagonists in anesthesia]. 854 33

Flumazenil, the first benzodiazepine antagonist, is currently used widely as an emergency drug, and has also been utilized in planned procedures, to time arousal intra- or post-operatively. It is known that flumazenil, used at the end of a procedure, causes instant recovery by reversing the residual effects of, for example, midazolam. An agonist-antagonist concept, midazolam-flumazenil, where benzodiazepine sedation or anaesthesia is terminated at will, is, therefore, finding increasing application. In neuroanaesthesia, for example, it facilitates immediate recovery, cardiovascular stabilization and the use of midazolam as an alternative to thiopentone and inhalational agents, and in ear, nose and throat endoscopies, it permits more rapid turnover of patients and is a good choice for haemodynamic stability in patients with a high cardiovascular risk factor. There continues to be debate over the term used to describe the level of sedation remaining after the effects of the antagonist have worn off. 'Resedation' is often used incorrectly to describe what is in reality residual sedation. Given the correct use of midazolam or the exploitation of synergism using opioids, flumazenil will cause arousal, while maintaining the benefit of opioid analgesia. Such a technique may eliminate the need for formal recovery facilities in many ambulatory patients, thereby reducing dependence on trolleys, beds and nurses. This has major implications for health economics, particularly in relation to endoscopy clinics and when co-induction of anaesthesia is employed.
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PMID:Flumazenil and midazolam in anaesthesia. 869 20

In the present study, the role of benzodiazepine-GABAA receptor complex in the attenuation of U-50,488H (U50), a selective kappa opioid agonist-induced analgesia and inhibition of tolerance to its analgesia by ginseng total saponin (GTS) was investigated using the mice tail-flick test. The intraperitoneal (i.p.) treatment of GTS (100 and 200 mg/kg) and diazepam (0.1-1 mg/kg) dose-dependently attenuated the U50 (40 mg/kg, i.p.)-induced analgesia. GTS (0.001-10 microg/ml) did not alter binding of [3H]naloxone to mice whole brain membrane. The attenuation effect of GTS (100 mg/ kg) and diazepam (0.5 mg/kg) on U50-induced analgesia was blocked by flumazenil (0.1 mg/kg, i.p.), a benzodiazepine receptor antagonist, and picrotoxin (1 mg/kg, i.p.), a GABAA-gated chloride channel blocker. However, bicuculline (1 mg/kg, i.p.), a GABAA receptor antagonist blocked the attenuation effect of diazepam (0.5 mg/kg) but not GTS (100 mg/kg) on U50-induced analgesia. Chronic treatment (day 4-day 6) of GTS (50-200 mg/kg) and diazepam (0.1-1 mg/kg) dose-dependently inhibited the tolerance to U50-induced analgesia. Flumazenil (0.1 mg/kg) and picrotoxin (1 mg/kg) on chronic treatment blocked the inhibitory effect of GTS (100 mg/kg) and diazepam (0.5 mg/kg) on tolerance to U50-induced analgesia. On the other hand, chronic treatment of bicuculline (1 mg/kg) blocked the inhibitory effect of diazepam (0.5 mg/kg) but not GTS (100 mg/kg) on tolerance to U50-induced analgesia. In conclusion, the findings suggest that GTS attenuates U50-induced analgesia and inhibits tolerance to its analgesia and this action involves benzodiazepine receptors and GABAA-gated chloride channels.
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PMID:Role of benzodiazepine-GABAA receptor complex in attenuation of U-50,488H-induced analgesia and inhibition of tolerance to its analgesia by ginseng total saponin in mice. 1200 18

This study assessed the effect of the central benzodiazepine receptor antagonist, 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid ethyl ester (flumazenil), on morphine-induced analgesia, locomotor effects, and development of tolerance in rats. The thermally evoked pain (tail flick) response was determined after acute and chronic intraperitoneal (i.p.) administration of morphine and flumazenil, alone and in combination. In acute studies, flumazenil induced weak analgesia unrelated to dose and sex, whereas morphine-induced analgesia was dependent on both dose and sex (male>female). Flumazenil dose-dependently enhanced the analgesic effect of morphine in female but not in male rats. Isobolographic analysis suggested synergism between flumazenil and morphine in female rats, but antagonism in male rats. Flumazenil-induced locomotor changes (alone and with morphine) were related to sex but not dose. Chronic coadministration of flumazenil with morphine enhanced analgesia and attenuated tolerance development in female rats. The findings suggest a possible role for flumazenil as an adjunct with opioids in acute and chronic pain therapy.
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PMID:Modification of morphine analgesia and tolerance by flumazenil in male and female rats. 1279 52

Melatonin, a primary secretory product of pineal gland, is known to produce many of its pharmacological actions via benzodiazepine-gamma-aminobutyric acidA (GABAA)ergic mechanisms. Recently, we showed that benzodiazepine-GABAAergic mechanisms play an important role in U-50,488H (U50) analgesia and its tolerance. Hence, in the present study, the effect of melatonin on U50 analgesia and its tolerance was investigated. Furthermore, the possible role of benzodiazepine-GABAAergic mechanisms in the actions of melatonin on U50 analgesia was investigated. All experiments were performed using the radiant tail-flick test for mice. Melatonin [0.2, 1 and 5 mg/kg, intraperitoneal (i.p.)] neither produced analgesia nor affected the acute U50 (40 mg/kg, i.p.) analgesia. Tolerance to U50 analgesia was induced by administering U50 (40 mg/kg, i.p.) twice daily over 6 days. Treatment with melatonin (1 and 5 mg/kg, i.p) 15 min prior to each dose of U50 inhibited the development of tolerance, whereas a low dose of melatonin (0.2 mg/kg, i.p.) did not. The inhibition of U50 tolerance by melatonin was reversed by the chronic treatment with flumazenil (0.1 mg/kg), a benzodiazepine receptor antagonist and picrotoxin (1 mg/kg), a GABAA-gated chloride channel blocker. Flumazenil and picrotoxin neither affected tail-flick latencies nor altered acute U50 analgesia and its tolerance. Interestingly, chronic 6-day melatonin treatment in a vehicle (U50-naive) group did not alter U50 analgesia measured on day 7. Together, these findings suggest that melatonin interferes with the neural mechanisms involved in the development of tolerance to U50 analgesia. The inhibition of U50 tolerance by melatonin was reversed by flumazenil and picrotoxin treatment, suggesting that benzodiazepine-GABAAergic mechanisms play an important role in the development of tolerance to U50 analgesia and that melatonin inhibits the development of U50 tolerance via benzodiazepine-GABAAergic mechanisms.
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PMID:Melatonin inhibits the development of tolerance to U-50,488H analgesia via benzodiazepine-GABAAergic mechanisms. 1558 81