Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0020672 (hypothermia)
17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous reports have shown that (+/-)-YM796 (2,8-dimethyl-3-methylene-1-oxa-8-azaspiro[4.5]decane) exhibits M1 agonistic activity and ameliorates cognitive impairment, and that the (-)-S isomer is active in in vitro studies. We report here the characterization of the (-)-S isomer, YM796 ((-)-(S)-2,8-dimethyl-3-methylene-1-oxa-8-azaspiro[4.5]decane L-tartrate monohydrate), and its (+)-R isomer in in vivo pharmacological studies in comparison with the cholinesterase inhibitors tacrine, amiridine and E-2020. YM796 (0.031-0.5 mg/kg p.o.), like the racemate, reversed the cognitive impairment in passive avoidance tasks of rats with nucleus basalis magnocellularis lesions, whereas (+)-R-YM796 was ineffective in this experimental amnesia. YM796 exhibited only weak effects on mouse salivation and hypothermia, a peripheral cholinergic response and a central cholinergic response, respectively. The (+)-R isomer, however, failed to induce these cholinergic responses. YM796 also ameliorated the memory deficits induced by scopolamine in rats and electroconvulsive shock in mice. The potency of YM796 in these experimental amnesia models was over a 100 times greater than that of tacrine, over 10 times greater than that of E-2020, and 6 times greater than that of amiridine. In salivary secretion and hypothermia, YM796 was 2-4 times weaker than tacrine and E-2020, and 1-2 times stronger than amiridine. Thus, YM796's ratio of anti-amnesic effects to salivary secretion and hypothermia was much greater than that of the cholinesterase inhibitors tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of a novel muscarinic receptor agonist, YM796: comparison with cholinesterase inhibitors in in vivo pharmacological studies. 787 30

The effects of physostigmine, tacrine and NIK-247 on scopolamine-induced impairment of a passive avoidance response were examined in rats. In addition, we investigated possible peripheral side-effects: miosis and salivation, and central side-effects: hypothermia and tremor which are mediated by cholinergic activation. Intraperitoneal injection of physostigmine reversed scopolamine-induced amnesia at a dose of 0.03 mg/kg. Antiamnesic effects of oral administration of tacrine and NIK-247 were observed at doses of 0.3 and 0.1-0.3 mg/kg, respectively. Intraperitoneal injection of physostigmine induced miosis, salivation, hypothermia and tremor at doses > or = 0.1, 0.3, 0.3 and 1 mg/kg, respectively. Oral administration of tacrine (at doses > or = 0.3 mg/kg) and NIK-247 (at doses > or = 3 mg/kg) produced miosis. Tacrine (at doses > or = 1 mg/kg) and NIK-247 (at doses > or = 3 mg/kg) produced hypersalivation. Hypothermia and tremor were observed after administration of tacrine (at doses > or = 10 mg/kg) and NIK-247 (30 mg/kg). The antiamnesic dose of physostigmine was 1/30-1/3 of doses with central or peripheral side-effects. The dose ratio of tacrine was 1/30-1; that of NIK-247 was 1/300-1/10. These results indicate that NIK-247 has higher safety and greater selectivity for cognitive functions than physostigmine or tacrine.
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PMID:Antiamnesic and cholinomimetic side-effects of the cholinesterase inhibitors, physostigmine, tacrine and NIK-247 in rats. 811 9

A nonbarbiturate anesthetic consisting of ketamine HCl (Ketaset) and xlyazine (Rompun) was administered to assess the effects of anesthesia on hypothermia-induced retrograde amnesia in Long Evans hooded and Sprague-Dawley albino rats. Results from Experiment 1a indicate that this anesthetic does not attenuate retrograde amnesia, and the findings from Experiment 1b suggest that awakening from Ketaset/Rompun anesthesia at normal body temperature (following administration of deep body cooling) does not attenuate the resulting hypothermia-induced retrograde amnesia. Experiment 2 demonstrated that various delays between training and hypothermia resulted in a temporal gradient that was the same for animals cooled while either conscious or under anesthesia. The results of Experiment 3 showed that rats made amnesic while under anesthesia did not recover the target memory if given a recooling treatment, but rats that were made amnesic while conscious did recover the memory with the same reminder treatment. These findings indicate that the conscious processing of stimuli associated with hypothermia treatment is not necessary in inducing hypothermia-induced retrograde amnesia, but that conscious processing is an important factor if the amnesia is to be recovered with a recooling treatment.
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PMID:Differential effects of Ketaset/Rompun anesthesia on hypothermia-induced retrograde amnesia and its recovery. 856 78

Induced recovery from amnesia appears similar to disinhibition effects obtained when response strength is weakened in various ways. Therefore, the possibility that reexposure to the amnestic treatment acts as a "disinhibitor" is problematic for a retrieval interpretation of recovery following amnesia. Two experiments examined the question of whether or not hypothermia treatment (i.e., deep body cooling) acts as a disinhibitor for an extinguished fear response in Sprague-Dawley rats. The results of Experiment 1 indicate that deep body cooling did not significantly disinhibit a passive-avoidance response that had previously been extinguished with a 4-min nonreinforced exposure to the shock chamber of the apparatus. Experiment 2 further examined this negative effect by using a modified passive-avoidance procedure and lengthening the extinction session from 4 to 12 min. Similar to Experiment 1, the results of the second experiment also suggested that if the subject's body temperatures were reduced prior to the retention test, no disinhibitory effect of fear conditioning was manifested. These findings support the notion that memory retrieval (i.e., the contextual cue explanation) is the basis for the alleviation of amnesia by reexposure to the amnestic agent.
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PMID:Does induced recovery from amnesia represent a disinhibition effect? 891 97

In studies of experimentally induced retrograde amnesia (RA), as the interval between training and the amnestic treatment is lengthened, amnesia decreases (4). This temporal gradient for RA has been reported with a wide variety of amnestic agents, including RA produced by thermoregulatory disturbances (8). This temporal gradient for RA is not unlike certain characteristics of classical conditioning, where weaker conditioned responding occurs when the interval between the conditioned stimulus (CS) and unconditioned stimulus (US) is lengthened. Furthermore, there is evidence that administration of anesthetics can lengthen the "effective conditioning" interval between the CS and US, as demonstrated in a conditioned taste-aversion (CTA) procedure (10). In that study, little conditioning was observed when a 3-h delay (or more) was incorporated between presentations of the CS (flavor) and the US (toxin). However, if subjects were anesthetized immediately after the CS was delivered and remained anesthetized during the CS-US interval, strong conditioning was observed with CS-US intervals of up to 9 h. The aim of the present experiment was to determine if the temporal gradient for hypothermia-induced RA could also be lengthened. That is, we tested whether the interval between training and hypothermia treatment could be lengthened by anesthetizing subjects with Ketaset-Rompun. The results indicate that the training-to-amnestic agent interval could be lengthened within moderate limits. The implications for hypothermia-induced RA is further discussed.
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PMID:Ketaset-Rompun extends the temporal gradient for hypothermia-induced retrograde amnesia. 1040

Hypoxia-induced cognitive deficits are mainly due to disturbances of the balance between the GABAergic and glutamatergic systems. Acquisition, consolidation and retention impairment in passive avoidance test, hypolocomotion in the open field test, an anxiogenic-like effect in the elevated plus-maze test and hypothermia were observed in rats subjected to hypoxia. Drugs which reduce glutamate release may possess neuroprotective activity. Both, agonists of GABA(B) (baclofen) and group III mGlu receptors (L-AP4) influence the release of glutamate. We studied the behavioral effects of baclofen on hypoxia-induced amnesia and the role of L-AP4 in these processes. Baclofen impaired acquisition, produced an anxiogenic-like effect and lowered body temperature but reduced the hypoxia-induced deficit of acquisition and consolidation of conditioned avoidance, diminished the anxiogenic-like effect, and reduced the motor inhibition produced by hypoxia. L-AP4 improved the acquisition, consolidation and retrieval processes as well as the hypoxia-induced consolidation deficit in the passive avoidance test. Co-administration of baclofen with L-AP4 improved consolidation and enhanced the baclofen activity vs. the respective group without hypoxia. In a group of rats that had undergone hypoxia, joint administration of baclofen and L-AP4 improved retrieval as well as enhanced the effect of baclofen and L-AP4 vs. their respective group without hypoxia. The agonist of group III mGluRs did not change locomotor activity but diminished baclofen-induced motility in rats without hypoxia. L-AP4 given alone or with baclofen produced an anxiogenic-like effect in rats without hypoxia but produced an anxiolytic-like effect in those that had undergone hypoxia. L-AP4 did not influence the activity of baclofen in the elevated plus-maze test. L-AP4 given alone or with baclofen did not change body temperature. It is concluded that baclofen and L-AP4 may cooperate in the consolidation process in rats without hypoxia and in retrieval of passive avoidance in animals that had undergone hypoxia. The observed interaction is probably the result of activation of the presynaptic receptors which influence glutamate and GABA release.
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PMID:Effects of baclofen and L-AP4 in passive avoidance test in rats after hypoxia-induced amnesia. 1653 35

The use of general anaesthetics has facilitated great advantages in surgery within the last 150 years. General anaesthesia is composed of several components including analgesia, amnesia, hypnosis and immobility. To achieve these components, general anaesthetics have to act via multiple molecular targets at different anatomical sites in the central nervous system. Much of our current understanding of how anaesthetics work has been obtained within the last few years on the basis of genetic approaches, in particular knock-out or knock-in mice. Anaesthetic drugs can be grouped into volatile and intravenous anaesthetics according to their route of administration. Common volatile anaesthetics induce immobility via molecular targets in the spinal cord, including glycine receptors, GABA(A) receptors, glutamate receptors, and TREK-1 potassium channels. In contrast, intravenous anaesthetics cause immobility almost exclusively via GABA(A) receptors harbouring beta3 subunits. Hypnosis is predominantly mediated by beta3-subunit containing GABA(A) receptors in the brain, whereas beta2 subunit containing receptors, which make up more than 50% of all GABA(A) receptors in the central nervous system, mediate sedation. At clinically relevant concentrations, ketamine and nitrous oxide block NMDA receptors. Unlike all other anaesthetics in clinical use they produce analgesia. Not only desired actions of anaesthetics, but also undesired side effects are linked to certain receptors. Respiratory depression involves beta3 containing GABA(A) receptors whereas hypothermia is largely mediated by GABA(A) receptors containing beta2 subunits. These recent insights into the clinically desired and undesired actions of anaesthetic agents provide new avenues for the design of drugs with an improved side-effect profile. Such agents would be especially beneficial for the treatment of newborn children, elderly patients and patients undergoing ambulatory surgery.
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PMID:Anaesthetic drugs: linking molecular actions to clinical effects. 1707 66

Two experiments were conducted using rats to determine whether extinction is susceptible to a traditional amnestic agent (i.e., hypothermia) and to examine whether amnesia for extinction follows the same characteristics as those that occur with original memories. In Experiment 1, rats received hypothermia immediately, 60 min, or 120 min after extinction. When tested, the subjects cooled shortly after extinction showed little memory of the extinction training. This amnesia for extinction disappeared with longer postextinction delays, demonstrating a temporal gradient. Experiment 2 replicated the basic finding and demonstrated that an amnestic-extinguished memory could be recovered by reexposing the subjects to the amnestic agent and that the recovered extinction memory did not persist. These findings provide more evidence that extinction is a form of new learning and are consistent with retrograde amnesia research for original memories showing a temporal gradient and alleviation of retrograde amnesia by reexposure to the amnestic agent.
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PMID:Retrograde amnesia for extinction: similarities with amnesia for original acquisition memories. 1791 18

Voltage-gated potassium channel antibody (VGKC-Ab)-associated limbic encephalitis (LE) is a recently described syndrome that broadens the spectrum of immunotherapy-responsive central nervous system disorders. Limbic encephalitis is typically characterised by a sub-acute onset of disorientation, amnesia and seizures, but the clinical spectrum is not yet fully defined and the syndrome could be under-diagnosed. We here describe the clinical profile of four patients with VGKC-Ab-associated LE who had intermittent, episodic hypothermia. One of the patients also described a prodrome of severe neuropathic pain preceding the development of limbic symptoms. Both of these novel symptoms responded well to immunosuppressive therapy, with concurrent amelioration of amnesia/seizures.
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PMID:Hypothermia in VGKC antibody-associated limbic encephalitis. 1820 10

The effects of hypothermia on memory formation have been examined extensively, and while it is clear that post-training cooling interferes with the process of consolidation, the nature of the temperature sensitive processes disrupted in this way remain poorly defined. Post-training manipulations that disrupt consolidation tend to be effective during specific time-windows of sensitivity, the timing and duration of which are directly related to the mechanism through which the treatment induces amnesia. As such, different treatments that target the same basic processes should be associated with similar time-windows of sensitivity. Using this rationale we have investigated the possibility that cooling induced blockade of long-term memory (LTM) stems from the disruption of protein synthesis. By varying the timing of post-training hypothermia we have determined the critical period during which cooling disrupts the consolidation of appetitive long-term memory in the pond snail Lymnaea. Post-training hypothermia was found to disrupt LTM only when applied immediately after conditioning, while delaying the treatment by 10 min left the 24 h memory trace intact. This brief (<10 min) window of sensitivity differs from the time-window we have previously described for the protein synthesis inhibitor anisomycin, which was effective during at least the first 30 min after conditioning [Fulton, D., Kemenes, I., Andrew, R. J., & Benjamin, P. R. (2005). A single time-window for protein synthesis-dependent long-term memory formation after one-trial appetitive conditioning. European Journal of Neuroscience, 21, 1347-1358]. We conclude that hypothermia and protein synthesis inhibition exhibit distinct time-windows of effectiveness in Lymnaea, a fact that is inconsistent with the hypothesis that cooling induced amnesia occurs through the direct disruption of macromolecular synthesis.
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PMID:Time-window for sensitivity to cooling distinguishes the effects of hypothermia and protein synthesis inhibition on the consolidation of long-term memory. 1879 38


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