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)

Plasma concentrations, maximum regional brain concentrations, and specific regional binding in the brain after administration of 0, 0.1, and 0.2 mg/kg doses of (S)-ketamine were measured in a randomized, double-blind, crossover study in five volunteers and were related to induced effects such as analgesia, amnesia, and mood changes. Specific binding in the brain was assessed by simultaneous administration of (S)-[N-methyl-11C]ketamine quantified by positron emission tomography. High radioactivities in the brain corresponded to regional distribution of N-methyl-D-aspartate receptor complexes. A significant and dose-dependent reduction of binding was measured as a result of displacement of (S)-[N-methyl-11C]ketamine. Memory impairment and psychotomimetic effects were related to dose, plasma concentration 4 minutes after administration, and decreased regional binding of (S)-ketamine in the brain and were consistently seen at plasma and maximum regional brain (S)-ketamine concentrations higher than 70 and 500 ng/ml, respectively. The magnitude of specific binding of (S)-ketamine, measured with positron emission tomography, can be related directly to drug effects.
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PMID:Central nervous system effects of subdissociative doses of (S)-ketamine are related to plasma and brain concentrations measured with positron emission tomography in healthy volunteers. 764 66

Cannabinoid receptors are molecular targets for marijuana and hashish, the widespread drugs of abuse. These receptors are expressed in areas of the central nervous system that contribute in important ways to the control of memory, cognition, movement and pain perception. Indeed, such functions can be strongly influenced by cannabinoid drugs, with consequences that include euphoria, analgesia, sedation and memory impairment. Although the pharmacology of cannabinoid drugs is now beginning to be understood, we still lack essential information on the endogenous signalling system(s) by which cannabinoid receptors are normally engaged. An endogenous ligand for cannabinoid receptors, anandamide, has been described. Here we report that sn-2 arachidonylglycerol (2-AG), a cannabinoid ligand isolated from intestinal tissue, is present in brain in amounts 170 times greater than anandamide. 2-AG is produced in hippocampal slices by stimulation of the Schaffer collaterals, an excitatory fibre tract that projects from CA3 to CA1 neurons. Formation of 2-AG is calcium dependent and is mediated by the enzymes phospholipase C and diacylglycerol lipase. 2-AG activates neuronal cannabinoid receptors as a full agonist, and prevents the induction of long-term potentiation at CA3-CA1 synapses. Our results indicate that 2-AG is a second endogenous cannabinoid ligand in the central nervous system.
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PMID:A second endogenous cannabinoid that modulates long-term potentiation. 928 89

This research determined the safety and efficacy of two small-dose infusions of dexmedetomidine by evaluating sedation, analgesia, cognition, and cardiorespiratory function. Seven healthy young volunteers provided informed consent and participated on three occasions with random assignment to drug or placebo. Heart rate, blood pressure, respiratory rate, ETCO(2), O(2) saturation, and processed electroencephalogram (bispectral analysis) were monitored. Baseline hemodynamic measurements were acquired, and psychometric tests were performed (visual analog scale for sedation; observer's assessment of alertness/sedation scale; digit symbol substitution test; and memory). The pain from a 1-min cold pressor test was quantified with a visual analog scale. After a 10-min initial dose of saline or 6 microg. kg(-1). h(-1) dexmedetomidine, volunteers received 50-min IV infusions of saline, or 0.2 or 0.6 microg. kg(-1). h(-1) dexmedetomidine. Measurements were repeated at the end of infusion and during recovery. The two dexmedetomidine infusions resulted in similar and significant sedation (30%-60%), impairment of memory (approximately 50%), and psychomotor performance (28%-41%). Hemodynamics, oxygen saturation, ETCO(2), and respiratory rate were well preserved throughout the infusion and recovery periods. Pain to the cold pressor test was reduced by 30% during dexmedetomidine infusion. Small-dose dexmedetomidine provided sedation, analgesia, and memory and cognitive impairment. These properties might prove useful in a postoperative or intensive care unit setting. IMPLICATIPNS: The alpha(2) agonist, dexmedetomidine, has sedation and analgesic properties. This study quantified these effects, as well as cardiorespiratory, memory and psychomotor effects, in healthy volunteers. Dexmedetomidine infusions resulted in reversible sedation, mild analgesia, and memory impairment without cardiorespiratory compromise.
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PMID:Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. 1070 60

Cannabinoids which impair rat working memory appear to inhibit hippocampal extracellular acetylcholine (Ach) release and reduce choline uptake through an interaction with CB1 cannabinoid receptors. Here we report that CP 55,940, a potent bicyclic synthetic cannabinoid analog, dose-dependently impaired rat performance, when given i.p. 20 min before an eight-arm radial maze test. The selective CB1 cannabinoid receptor antagonist SR 141716A, given i.p. 20 min earlier, significantly reduced the memory deficit Pretreatment with eptastigmine, a second generation cholinesterase inhibitor, given orally 100 min before the cannabinoid agonist, relieved the memory impairment without affecting CP 55,940-induced behavioural alterations such as reduced spontaneous motor activity, analgesia and hind limb splaying. These data suggest that cannabinoid-induced working memory impairment is mediated through a central cholinergic blockade.
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PMID:Cannabinoid-induced working memory impairment is reversed by a second generation cholinesterase inhibitor in rats. 1088 65

The antagonistic effect of pseudoginoside-F11 (PF(11)) on the various actions of morphine was studied in mice. The results demonstrated that PF(11), at the doses of 4 and 8 mg/kg, PO, significantly inhibited morphine (10 mg/kg, SC)-induced memory impairment in the Morris water maze test. PF(11), at 4 mg/kg, PO, did not influence conditioned place preference per se, yet markedly blocked the conditioned place preference to morphine. PF(11), at the doses of 4 and 8 mg/kg, PO, also significantly antagonized morphine (5 mg/kg, SC)-induced analgesia tested by tail pinch method. PF(11), at 4 mg/kg, PO, did not influence locomotor activity per se, yet inhibited the development of the reverse tolerance, as shown by the increase in locomotor activity, to morphine. At the doses of 4 and 8 mg/kg, PO, PF(11) significantly antagonized the development of analgesia tolerance to morphine in the tail pinch test. Thus, the above results demonstrate for the first time that PF(11) can antagonize some actions of morphine. However, the mechanism of action of PF(11) merits further evaluation.
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PMID:Antagonistic effect of pseudoginsenoside-F11 on the behavioral actions of morphine in mice. 1089 76

This placebo-controlled, randomized study evaluated, on separate days, the dose-response relationship for 1 h infusions of clonidine 1, 2 and 4 microg kg(-1) h(-1), in eight healthy volunteers aged 22-30 yr. Response end-points included sedation (bispectral index, visual analogue scale and observer assessment of sedation), analgesia to a cold pressor test, memory (recall of word lists), cognitive function (digit symbol substitution test (DSST)), respiratory function (respiratory rate, end-tidal carbon dioxide, oxygen saturation) and haemodynamic stability (heart rate and mean arterial pressure). Clonidine infusions resulted in significant and progressive sedation, but all subjects were easily awoken to perform tests and evaluations. Statistically significant analgesia, memory impairment and reduced performance on the DSST occurred during 4 microg kg(-1) h(-1) infusions (resulting in a plasma concentration of 2 ng ml(-1). There were no statistically significant changes in cardiorespiratory variables throughout the study.
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PMID:Sedative, analgesic and cognitive effects of clonidine infusions in humans. 1157 9

The cannabinoid signaling system is composed of cannabinoid (CB) receptors, their endogenous ligands, the endocannabinoids, and the enzymes that produce and inactivate them. It is well known that neurons communicate between each other through this signaling system. Delta 9-tetrahydrocannabinol, the main psychoactive compound of marijuana, interacts with CB receptors, impinging on this communication and inducing profound behavioral effects such as memory impairment and analgesia. Recent evidence suggests that glial cells also express components of the cannabinoid signaling system and marijuana-derived compounds act at CB receptors expressed by glial cells, affecting their functions. This review summarizes this evidence, discusses how glial cells might use the cannabinoid signaling system to communicate with neighboring cells, and argues that nonpsychotropic cannabinoids, both marijuana-derived and synthetic, likely constitute lead compounds for therapy aimed at reducing acute and chronic neuroinflammation, such as occurs in multiple sclerosis.
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PMID:Cannabinoid signaling in glial cells. 1539 Jan 10

(-)-3-Acetyl-6beta-acetylthio-N-cyclopropylmethyl-normorphine (KT-90) is a synthesized compound that binds to mu-, delta- and kappa-opioid receptors in vitro. KT-90 induces analgesia in the tail-flick test and this effect is antagonized by nor-BNI, a selective kappa-opioid receptor antagonist. However, lower doses of KT-90 antagonize morphine-induced analgesia. We reported that kappa-opioid receptor agonists such as U-50,488H and dynorphin A (1-13), improved scopolamine-induced impairment of learning and memory in mice and/or rats. In this study, the effects of KT-90 were investigated in an acetic acid-induced writhing test and scopolamine-induced memory impairment test using spontaneous alternation performance in a Y-maze. Male ddY mice were treated with scopolamine (1.65 micromol/kg, s.c.) 30 min before the behavioral test. KT-90 (0.07-2.35 micromol/kg, s.c.) was injected 30 min before testing. In the writhing test, the antinociceptive effect of KT-90 (0.71 micromol/kg) was completely antagonized by a selective mu-opioid receptor antagonist, beta-funaltrexamine (10.2 nmol/mouse, i.c.v.) and partially antagonized by nor-BNI (4.9 nmol/mouse, i.c.v.), but it was not antagonized by a selective delta-opioid receptor antagonist, naltrindole (9.1 pmol/mouse, i.c.v.). KT-90 significantly improved the impairment of spontaneous alternation induced by scopolamine. The ameliorating effect of KT-90 was not antagonized by nor-BNI, but was almost completely antagonized by a selective sigma receptor antagonist, NE-100 (2.6 micromol/kg, i.p.). These results suggested that the KT-90-induced antinociceptive effect was mediated by mu- and partially by kappa-opioid receptors, and the KT-90-induced improvement in scopolamine-induced impairment of spontaneous alternation was mediated mainly via sigma receptors.
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PMID:Pharmacological characterization of the ameliorating effect on short-term memory impairment and antinociceptive effect of KT-90 in mice. 1586 34

Morphine and other potent opioids are frequently used in palliative care and pain management. When sustained-release (SR) opioids do not provide adequate background analgesia, additional immediate-release (IR) opioid (e.g. short-acting morphine) may be required to alleviate breakthrough or episodic pain. Despite the frequent use of IR morphine on top of SR opioids, little is known about the effects of such treatment on patients' everyday cognitive functioning. This study therefore used a double-blind, placebo-controlled, cross-over design to assess cognitive functioning in 14 patients receiving palliative care. All patients were taking SR opioid preparations and required <or=2 doses of IR morphine/day. Performance on cognitive measures (as well as subjective measures of pain and mood) after a dose of IR morphine was compared with placebo. Patients experienced significantly more pain-reduction following IR morphine (P=0.03), while other measures of subjective drug effects (e.g. sedation) were largely unaffected. Patients displayed anterograde memory impairment after IR morphine relative to placebo (P=0.003). Intriguingly, patients also had significant 'retrograde' memory impairment: delayed recall of verbal information presented before IR morphine also declined (P=0.024). In addition, IR morphine reduced performance on a complex tracking task (Reitan's trails B; P=0.03) whilst enhancing it on a simpler tracking task (Reitan's trails A; P=0.03). In conclusion, this study suggests that IR morphine, when taken on top of a SR opioid, produces transient anterograde and retrograde memory impairments and a decrement in two-target tracking. These impairments may impact negatively on patients' everyday functioning.
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PMID:The effects of immediate-release morphine on cognitive functioning in patients receiving chronic opioid therapy in palliative care. 1619 1

The present study was undertaken to investigate the antagonistic effects of the methanolic extract of Polygala telephioides (PT) on morphine responses in mice. Single administration of PT tended to antagonize the morphine-induced analgesia in a hot-plate test. Moreover, PT (300 mg/kg, p.o.) improved the morphine-induced memory impairment in an elevated plus maze test. However, PT alone had no effect on behaviors in the open-field, hot-plate and elevated plus maze tests. We investigated the effects of PT on naloxone-induced jumping (as withdrawal sign) in morphine-dependent mice. To induce dependence, mice were twice daily treated with morphine (10-45 mg/kg, s.c.) for 5 days. Co-administrations of PT (10, 100 and 300 mg/kg, p.o.) during repeated morphine treatments significantly suppressed the naloxone (10 mg/kg, i.p.)-induced jumping. However, the naloxone-induced jumping was not affected by a single large administration of PT on the 5th day. The inhibitory effect of PT on the naloxone-induced jumping was due to the development of dependence rather than expression of withdrawal sign. Moreover, single administration of PT (30 mg/kg, p.o.) decreased the morphine levels in plasma. These results indicate that PT may be useful in facilitating narcotic detoxification.
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PMID:Antagonistic effects of methanolic extract of Polygala telephioides on morphine responses in mice. 1620 47


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