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)

Use of selective delta opioid antagonists provide evidence that the delta receptor within the brain seems an integrated part in the mediation of respiratory depression induced by a potent analgesic like fentanyl. Low doses of the delta antagonists RX-8008M (3-6 micrograms/kg) as well as ICI 174,864 (3-6 micrograms/kg) reversed fentanyl-related respiratory depression (arterial blood gases) in the unanesthetized canine. Opioid-induced blockade of afferent sensory nerve volleys (amplitude height of the somatosensory-evoked potential) could be reversed only by a high dose (9 micrograms/kg) of RX-8008M. Depression of amplitude height of the SEP could not be reversed by ICI 174,864 over the whole dose range (3-6-9 micrograms/kg). In comparison, naloxone (1-5-10 micrograms/kg) not only reversed depression of PaO2, it also reversed the blockade of afferent sensory nerve impulses in the low (5-micrograms/kg)-dose range. A highly selective delta antagonist may have a therapeutic value in reversing opioid-related respiratory depression, resulting in little or no attenuation of analgesia.
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PMID:Opioid-induced respiratory depression and analgesia may be mediated by different subreceptors. 185 Aug 27

An inhibitor of hepatic uroporphyrinogen decarboxylase (EC 4.1.1.37) was demonstrated in heat-treated extracts of livers from C57BL/10ScSn mice with iron overload after a single dose (100 mg/kg; 350 mumol/kg) of hexachlorobenzene (HCB). Inhibition was not due to accumulated uroporphyrin since this could be removed by a SEP-PAK C18 cartridge without affecting inhibitor activity. The presence of the inhibitor could be first demonstrated 2 weeks after mice received HCB and before major elevation of hepatic porphyrin levels. Maximum inhibitory potential was reached at about 8 weeks and was still detected 25 weeks after the chemical, thus paralleling the depression of enzyme activity reported previously [Smith, Francis, Kay, Greig & Stewart (1986) Biochem. J. 238, 871-878]. The inhibitor was not detected following treatment of mice with either iron or HCB alone or after the decarboxylase activity was destroyed in vitro by the combination of uroporphyrin and light. The formation of the inhibitor by inbred mouse strains nominally Ah-responsive (C57BL/6J, C57BL/10ScSn, BALB/c, C3H/HeJ, CBA/J and A/J) and Ah-nonresponsive (SWR, AKR, 129, SJL, LP and DBA/2) did not correlate fully with their reported Ah-phenotype. There was a correlation amongst the Ah-responsive strains only, with hepatic ethoxyphenoxazone de-ethylase activity induced in parallel experiments by treatment with beta-naphthoflavone. De-ethylase activity induced by HCB, however, was considerably less than that with beta-naphthoflavone, which has not been reported as porphyrogenic. Other polyhalogenated chemicals, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,4,2',3',4'-hexachlorobiphenyl and hexabromobenzene, also caused the formation of the inhibitor of uroporphyrinogen decarboxylase.
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PMID:Chemically-induced formation of an inhibitor of hepatic uroporphyrinogen decarboxylase in inbred mice with iron overload. 367 56

The development of dog electrophysiological models for studying the treatment of cerebral arterial air embolism and spinal cord decompression sickness, required that the effects of the treatment gases on spinal and cortical somatosensory evoked potentials (SEP and CEP) be known. We found an inverse linear relationship between CEP amplitude and air pressure to 230 ft. An asymptote was approached when pressure was increased to 300 ft. This effect was not seen with 20% oxy-helium. The waves representing local cord events were depressed to a lesser extent than were the CEPs. We were able to detect an equilibration time in the EP suppression comparable to estimated inert gas wash-in time for the brain. A small depression of CEPs that did not reach significance was seen with exposure to 2.8 bar of oxygen and continuous exposure for up to 120 min caused no further diminution in amplitude than would be caused by time alone.
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PMID:The effects of various gases on cortical and spinal somatosensory evoked potentials at pressures up to 10 bar. 683 45

To confirm and extend previous findings concerning evoked potential (EP) changes produced by lithium carbonate (Li), 12 depressive patients were studied while on placebo and on therapeutic doses of Li. Four kinds of EPs were recorded from 14 leads: somatosensory (SEP) to left (LSEP) and right (RSEP) median nerve stimuli; visual (VEP) to a checkerboard flash; auditory (AEP) to binaural click. Plasma and erythrocyte (RBC) Li levels and Hamilton Depression ratings were obtained. Li produced a number of amplitude changes in EPs of all sensory modalities, while there were few latency changes; in general, amplitudes of positive components were increased, while negative component amplitudes were reduced. The spatial distributions of EP peaks were mainly unaltered by Li. The amount of EP amplitude change with Li tended to be correlated with plasma and RBC Li levels. No convincing correlations were found between alterations in EPs and depression ratings. The nature of the EP changes with Li was generally not concordant with normalization of the deviant EP characteristics found in depressives. The findings indicate that Li produces more widespread CNS changes than suggested by previous reports; it appears that these tend to be related to Li levels, but not to the therapeutic effects of Li.
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PMID:Cerebral evoked potential changes produced by treatment with lithium carbonate. 722 81

Neurobehavioral and electrophysiologic studies were carried out to determine the effect of diabetes mellitus on brain function. Fifty one non-insulin-dependent diabetic patients were compared with 30 nondiabetic controls that are equally matched in age, sex and educational level. The aim of this study was to determine the change of brain function in diabetics, and to evaluate the correlation between brain function and clinical factors. The results showed: In the diabetic group, 'the Clinical Memory Test' performances on MQ, the five subtests were respectively lower than those of the controls. 'The Fourth Exception Test', 'the Motor Stability Test' and 'the Hospital Anxiety and Depression Scale' results were significantly disordered, too. The latencies of wave I, III, V of BAEP, wave N65 P100 N125 P160 of VEP, wave P1 N1 P2 N2 N3 P4 of SEP and the interpeak latency of I-V of BAEP were prolonged significantly compared with the controls. Within the diabetics, there was correlation between I-V interpeak latency of BAEP, P100 peak latency of VEP and serum creatinine. These results demonstrate that brain dysfunction are present in NIDDM, and these brain dysfunction correlate with the kidney function.
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PMID:[Decreased brain function in patients with non-insulin-dependent diabetes mellitus]. 760 81

To check for suspected opioid-receptor mediated hypnotic and antinociceptive effects of S(+)-ketamine, highly selective antagonists were used after the anaesthetic. METHODS. To determine the hypnotic effects of increasing doses of S(+)-ketamine (2-5-10-20 mg/kg given at 10-min intervals), EEG power spectra (delta, theta, alpha, beta) were derived (Lifescan), and antinociceptive potency was evaluated using the somatosensory evoked potential (SEP, Lifescan) in awake, trained dogs (n = 10). To check for an opioid-receptor-related interaction, an antagonist of the methoxymorphinane series (HS-275, 80 micrograms/kg i.v.) with higher selectivity than naloxone for the mu-receptor was given at the end. After washout the same animals were exposed to S(+)-ketamine. This time, however, the highly selective delta-antagonist naltrindole (160 micrograms/kg i.v.) was given. To show up any respiratory depression arterial blood gases were taken after each dose. RESULTS. S(+)-Ketamine induced a dose-related increase in power in the theta band (3-8 Hz), with a ceiling effect at 10 mg/kg. The changes were reversed by both antagonists. In the beta band (13-30 Hz) and in the delta domain, power decreased or increased, respectively, in a highly significant manner (P < 0.005) at 20 mg/kg. Both effects reversed after the antagonists with an overshoot in beta (+12% and +14%, respectively) and a decrease in delta (-45% and -62%, respectively) compared with control. S(+)-Ketamine induced a dose-dependent increase in peak latency and depression of the SEP amplitude by a maximum of over 50%. Latency changes were completely reversed only by HS-275. Amplitude height was only partly restored by both antagonists. A clinical relevant decrease in PaO2 and increase in PaCO2 increase were seen at 20 mg/kg. Hypoxia was reversed by both antagonists; hypercapnia was only partially reversed. CONCLUSION. The results confirm the suspicion that S(+)-ketamine induces an opioid theta- and delta-receptor-mediated deep hypnotic effect. Blockade of nociceptive impulses in afferent sensory nervous pathways suggests an efficient analgesic effect mediated partly by the opioid mu-receptor. Other mechanisms, such as an interaction with the NMDA receptor, have to be taken into consideration to account for the full antinociceptive effect. Respiratory depression may be of clinical importance when high dosages of S(+)-ketamine are given.
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PMID:[Interaction of S-(+)-ketamine with opiate receptors. Effects on EEG, evoked potentials and respiration in awake dogs]. 784 Apr 15

Tramadol, an analgesic with mean potency one tenth that of morphine is used regularly for the treatment of chronic and postoperative pain. Previous reports have indicated that tramadol may induce seizure activity when given together with a selective serotonin reuptake inhibitor (SSRI). Therefore, its major mode of action may be questioned which purportedly is due to binding with the opioid receptor and partly due to the inhibition of monoamine reuptake. We therefore set out to study its potential in inducing seizure activity and to quantify its effect on EEG-power spectra and on the central modulation of sensory afferents in awake and trained dogs (n=7). In order to demonstrate if opioid receptors mediated these effects, incremental doses of tramadol were given which was followed by naloxone for possible reversal. After a wash-out period the same animals were exposed to graded doses of alfentanil, a pure mu-receptor agonist. Again this was followed by the opioid antagonist naloxone for reversal.The electroencephalogram (EEG) and the event-related evoked potentials (SEP) were used to demonstrate possible excitatory effects. In order to derive the SEP the front paw was stimulated electrically (Digi Stim II trade mark ) while the evoked potentials were picked up contralaterally from the somatosensory cortex using stick-on electrodes. 256 sweeps were averaged (Lifescan) and the peak-to-peak amplitude was measured to demonstrate CNS excitation compared to control (%). Additionally, the raw electroencephalogram was viewed for epileptogenic changes and its power computed into the various power bands alpha, beta, delta und theta using FFT over a time epoch of 60 s. Following control, graded doses of either tramadol (2-5-10 mg/kg i.v.) or alfentanil (10-30-60 microg/kg i.v.) were given every 15 min while the EEG and the SEP were recorded. Thereafter naloxone (20 microg/kg i.v.) was injected for reversal. Tramadol did not suppress the amplitude of the SEP at any dose. High doses (>5 mg/kg i.v.) resulted in an increase (+100%) of the amplitude of the evoked potential. This was accompanied by short-term muscle fibrillations, and a short-term spike-and-wave activity in the EEG followed by a long-lasting theta-dominance. These effects could not be reversed by naloxone. In contrast to tramadol, alfentanil induced a dose-related depression of amplitude in the SEP with a maximum of 82% suggesting a depressive effect of modulation of afferents in the sensory cortex. This effect was fully naloxone reversible and was followed by a rebound in amplitude of the SEP together with an increase in fast beta-waves in the EEG. Tramadol very little mediates its central action via the mu-opioid receptor as the present effects were not naloxone reversible. Consistent with the results is the very low affinity of tramadol to the opioid receptor which is several thousand times less than that of morphine. Most likely, inhibition of central norepinephrine and serotonin reuptake as well as the reduction in 5-HT-turnover may contribute to the effects of tramadol. Due to the monoamine reuptake inhibition an increase in transmission may result, triggering off excitatory phenomena with spike-and-wave activity in the CNS. Such excitatory effects, however, may only be seen when tramadol is used in doses exceeding the therapeutic range.
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PMID:[The opioid tramadol demonstrates excitatory properties of non-opioid character--a preclinical study using alfentanil as a comparison]. 1279 88

Fatigue in multiple sclerosis is a frequent and disabling symptom that can interfere in daily functioning. The aim of this study is to demonstrate the relationship between fatigue and disability, disease course, depression and quality of life. We administered French valid versions of the Fatigue Impact Scale (EMIF-SEP), the short form of the Beck depression inventory (13 items) and the SF-36 to 237 out of 312 patients with clinically definite multiple sclerosis with EDSS<or=6.5. The EMIF-SEP is composed of four dimensions (cognitive, physical, social role and psychological) and allows a multidimensional evaluation. Using a multivariate analysis, EMIF-SEP total scores with physical and social role subscales were highly correlated with EDSS (p < 0.0001). Cognitive and psychological dimensions of the EMIF-SEP were not linked to EDSS. EMIF-SEP was not correlated with disease course after adjusting for EDSS. EMIF-SEP scores were significantly associated with depression scores (r = 0.74, p < 0.0001). The multivariate analysis also showed a significant impact of fatigue on each scale of quality of life of the SF-36. These data confirm that fatigue is correlated with disability, but cognitive and psychological dimensions of fatigue remain independent. Fatigue is also associated with depression and quality of life.
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PMID:Fatigue in multiple sclerosis is related to disability, depression and quality of life. 1643 57

Detecting cognitive dysfunction may be clinically important during the early stages of multiple sclerosis (MS). We assessed a self-report questionnaire on cognitive complaints and individual neuropsychological tests to select patients with early relapsing-remitting MS (RRMS) who needed comprehensive cognitive testing. Fifty-seven patients underwent neurological and neuropsychological assessment, including Rao's Brief Repeatable Battery (BRB) and the complete SEP-59 Questionnaire, a French adaptation of the MSQOL-54, which contains four specific questions about self-perception of cognitive functions. Predictive values, specificity, sensitivity and accuracy of five individual neuropsychological tests--Selective Reminding Test, Symbol Digit Modalities Test (SDMT), Similarities Subtest, PASAT and Stroop Test--were calculated to predict cognitive impairment. Only 10.5% of patients did not report any cognitive complaint, while most reported complaints. On the basis of cognitive performances, 59.7% of patients were classified as cognitively impaired, although only one cognitive score was correlated with cognitive complaints. Depressive symptoms and fatigue were associated with more cognitive complaints. Sensitivity of the SDMT to predict cognitive impairment was 74.2%, specificity was 76.9% and accuracy was 75.4%. Since, at this stage, patients' cognitive complaints are already influenced by depression and fatigue and do not accurately reflect cognitive performances, the SDMT may help to select patients for testing with a more complete cognitive battery.
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PMID:How to detect cognitive dysfunction at early stages of multiple sclerosis? 1690 Jul 58

The 39th Annual Meeting of the Society for Neuroscience (SFN), held in Chicago, included topics covering new therapeutic developments in the field of neuroscience. This conference report highlights selected presentations on novel neuroprotective and antiparkinsonian agents, and compounds in development for the treatment of dementia, schizophrenia, depression, obesity and spinal muscular atrophy. Investigational drugs discussed include velusetrag and TD-8954 (both from Theravance Inc), SEP-228791 and SEP-226330 (both from Sepracor Inc), ADL-5510 (Adolor Corp), PF-217830 (Pfizer Inc), KB-099520 (Karo Bio AB), tesofensine (NeuroSearch A/S) and TRP6-01 (Theraptosis).
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PMID:Society for Neuroscience - 39th Annual Meeting. Part 2 - Novel therapies for neurodegenerative disorders and other CNS diseases. 1994 11


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