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)

1. The general pharmacology of buprenorphine, a potent analgesic agent derived from oripavine, is described. 2. After cute administration of buprenorphine, the spontaneous locomotor activity of mice was increased; rats displayed stereotyped licking and biting movements; behavioural depression was marked in guinea-pigs but mild in rhesus monkeys. The behaviour of cats was unchanged. 3. In general, buprenorphine reduced heart rate but had no significant effect on arterial blood pressure in conscious rats and dogs. 4. In anaesthetized, open-chest cats buprenorphine (0.10 and 1.0 mg/kg, i.v.) caused no major haemodynamic changes. 5. Buprenorphine (0.01-10 mg/kg i.a.) and morphine (0.30-30 mg/kg, i.a.) increased arterial PCO2 values and reduced PO2 values in conscious rats. With doses of buprenorphine greater than 0.10 mg/kg (a) the duration of respiratory depression became less, (b) ceiling effects occurred such that the maximum effects produced were less than those obtained with morphine. 6. Buprenorphine was a potent and long-lasting antagonist of citric acid-induced coughing in guinea-pigs. 7. At a dose level 20 times greater than the ED50 for antinociception (tail pressure), morphine suppressed urine output to a greater extent than the corresponding dose of buprenorphine in rats. 8. Over the range 0.01-1.0 mg/kg (s.c.), buprenorphine slowed the passage of a charcoal meal along the gastrointestinal tract in rats. After doses in excess of 1 mg/kg, the meal travelled increasingly further such that the distances measured at 10 and 30 mg/kg did not differ significantly from control values. In contrast, the morphine dose-response relationship was linear.
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PMID:The animal pharmacology of buprenorphine, an oripavine analgesic agent. 40 49

The purpose of this 2 factorial designed study was to investigate the influence of citric acid on the availability of zinc from diets containing 140 g corn germs as a native phytate source (0.5% phytate in diet). Growing male rats with an average initial weight of 42 g were divided into 8 groups of 8 animals each. After a 7 d depletion period (2.4 micrograms Zn/g diet) the animals were fed ad libitum for 21 d a diet on the basis of egg white solid and corn germs. The diets were supplemented with zinc in order to obtain phytate:zinc molar ratios of 31, 20, 14, and 0 (control without corn germs, 11 micrograms Zn/g diet). Each diet was fed with and without a supplementation of 1% citric acid. A phytate:Zn molar ratio of 31:1 resulted in typical symptoms of zinc-deficiency like anorexia, alopecia and a significant depression of growth. These effects were apparently reduced by citric acid. The zinc concentration in serum and organs followed the graded levels of phytate:zinc molar ratios. Primary significant effects of the phytate:Zn molar ratio but also effects of citric acid and interactions between the 2 factors phytate:Zn and citric acid could be detected. Only total liver zinc but not liver zinc based on fresh matter was affected by the phytate:Zn molar ratio. In serum and tissues the activity of alkaline phosphatase showed a significant response to the phytate:zinc molar ratio. Furthermore the supplementation with citric acid increased the femur alkaline phosphatase and slightly reduced it in the liver. The concentrations of metallothionein in liver duodenum, jejunum and ileum were significantly affected by the phytate:Zn molar ratio.
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PMID:[The effect of a supplement of citric acid on the bioavailability of zinc from corn germ]. 233 19

1. Antitussive, antinociceptive and respiratory depressant effects of codeine, morphine and H.Tyr.D-Arg.Gly.Phe(4-NO2) Pro.NH2 (compound BW443C) were investigated in unanaesthetized guinea-pigs. Antagonism of the antitussive and antinociceptive effects was investigated by the use of nalorphine and N-methylnalorphine. Naloxone was used to antagonize respiratory depression. 2. Antitussive ED50s (with 95% confidence limits) for inhibition of cough induced by citric acid vapour were for codeine, morphine and BW443C respectively, 9.1(5.8-15), 1.3(0.7-2.4) and 1.2(0.6-2.6) mg kg-1 s.c. and 8.7(4.2-12), 1.6(1.2-1.9) and 0.67(0.002-3.3) mg kg-1, i.v. The antitussive effects of subcutaneous codeine (25 mg kg-1) morphine (8.1 mg kg-1) and BW443C (2.5 mg kg-1) were significantly antagonized by subcutaneous nalorphine (3.0 mg kg-1) and N-methylnalorphine (3.0 mg kg-1). 3. In the multiple toe-pinch test, the antinociceptive ED50s (with 95% confidence limits) of codeine and morphine were 18(16-22) and 2.3(0.4-4.3) mg kg-1, s.c., respectively. Compound BW443C was ineffective in doses of 2.5 and 10 mg kg-1 s.c., a result consistent with its lacking penetration into the CNS. Subcutaneous nalorphine (3.0 mg kg-1) antagonized the antinociceptive action of codeine (25 mg kg-1) and morphine (8.1 mg kg-1). In contrast, N-methylnalorphine (3.0 mg kg-1) had no significant effect on the antinociceptive action of codeine and morphine, suggesting lack of penetration of the CNS by N-methylnalorphine. 4. At doses near to the i.v. ED50 values for the antitussive activity, morphine (1.5mg kg- ', i.v.) and codeine (10mg kg-', i.v.) caused small but significant depressions of ventilation (7.0 +/- 2.3% and 16.5 +/- 8.4% respectively). Higher doses of morphine (10, 30 and 60mg kg- ', i.v.) caused further doserelated depression of ventilation (9.6 +/- 5.3%, 22.4 +/- 6.2% and 36.2 +/- 9.6% respectively) whereas codeine (30 and 60mg kg-' i.v.) caused stimulation of ventilation which was marked (191.3 +/- 43.9%) at 60 mg kg-'. 5. Compound BW443C in doses of 1 or 10mgkg-',i.v. (approximately equal to, and 10 times the EDo for antitussive activity) did not cause significant depression of ventilation. Only at higher doses of 30 and 60mg kg-', i.v. was there a significant decrease in minute volume (13.1 +/- 6.8% and 15.9 +/- 1.89% respectively). The depression of ventilation caused by either BW443C (60mg kg-', i.v.) or morphine (60mg kg-', i.v.) was prevented by pretreatment with naloxone (3mg kg-', i.v.) administered 15 min before morphine or BW443C. 6. These results in the guinea-pig support the hypothesis that the antitussive action of the opiates codeine and morphine and the opioid pentapeptide BW443C do not require penetration of these drugs into the CNS.
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PMID:Effects of codeine, morphine and a novel opioid pentapeptide BW443C, on cough, nociception and ventilation in the unanaesthetized guinea-pig. 334 36

Ketonuria has been observed in alcoholics. To study the mechanism of this effect, healthy, volunteers were given adequate diets (36% of calories as lipid and 15% as protein) for 18 days, with isocaloric replacement of carbohydrate (46% of calories) by either ethanol or additional fat. The latter resulted in a high fat diet, with 82% of calories as lipid. After about 1 wk of alcohol, massive and persistent ketonuria developed. Compared with the control period, there was a 30-fold increase in fasting blood acetoacetate and beta-hydroxybutyrate (P < 0.001). With the high fat diet, acetoacetate and beta-hydroxybutyrate increased 8- to 10-fold (P < 0.001). In the postprandial state, ethanol also induced hyperketonemia, but less markedly than when ethanol followed an overnight fast. With low fat diets (5% of calories), alcohol (46% of total calories) did not induce ketonuria or hyperketonemia, suggesting that a combination of alcohol and dietary fat is necessary. The addition of alcohol to rat liver slices did not affect ketogenesis. In rats pretreated with alcohol for 3 days, however, ketonemia developed, hepatic glycogen was decreased, and liver slices (incubated with palmitate-(14)C and glucose) had a significant increase in acetoacetate production, when compared to carbohydrate pretreated controls. Alcohol pretreatment or addition of alcohol in vitro had no effect on acetoacetate utilization by rat diaphragms, and decreased only slightly the conversion of beta-hydroxybutyrate-(14)C to (14)CO(2). Thus, the hyperketonemia and ketonuria observed after alcohol consumption cannot be attributed to an immediate effect of alcohol, but is the consequence of a delayed change in intermediary metabolism characterized by increased hepatic ketone production from fatty acids, possibly linked to ethanol-induced glycogen depletion and depression of citric acid cycle activity.
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PMID:Effect of ethanol on ketone metabolism. 545 93

The effect of 14 days' intake of mounting quantities of fats and energy on a constant optimum utilizable amount of dietary protein was studied in weaned rats weighing 60 g. Growth (PER, NPR) and utilization (NPU--body, LPU--liver) parameters of biological protein value were determined, supplemented by a study of the course of the antithetical processes of gluconeogenesis and glycolysis, of the pentose cycle, the citric acid cycle and of transamination processes in the animals' liver. According to the maximum PER, NPR, NPU and LPU values, a 14 days' intake of 59.2 g fats and 4.518 MJ, corresponding to a diet containing 10% protein, 30% fat and 2.274 MJ, had the best effect on the optimum utilizable amount of casein (21 g/14 days). A diet containing 35% and 40% fat stimulated gluconeogenesis, followed by a transamination process and inhibition of glycolysis, the citric acid cycle and lipogenesis (depression of pentose cycle activity and a decrease in the amount of body fat), and simultaneously reduced the values of all four parameters of protein biological value. The results demonstrate that very best diet for newly weaned rats is one containing 10% high quality protein, 30% fat and 2.274 MJ.
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PMID:Protein utilization in correlation to energy intake. 644 4

1. The relationship between coughing and spinal monosynaptic reflexes (SMR) in extensors and flexors was investigated in eight healthy subjects by using the Hoffmann technique. Coughing exerted major depression (81% in extensor and 83% in flexor SMR). This depressant effect began simultaneously with the first cough and lasted through the coughing phase. Complete recovery to initial values occurred an average of 40 s thereafter. 2. In comparison, mental tasks induced only a slight decrease in SMR amplitude. In contrast, the Mueller and Valsalva manoeuvres induced facilitation. 3. During coughing, large variations in extensor amplitudes were observed that were coupled with the ventilatory cycle. Slight facilitation was observed during inspiration, but expiration induced pronounced depression, occurring 0.20 s after the beginning of the expiratory period. Experiments performed during baseline breathing failed to show any change throughout inspiratory or expiratory phases. 4. Chemical stimulation of irritant receptors (inhalation of citric acid) produced no specific modification of extensor responses compared with the effect of placebo inhalation (distilled water). 5. These data suggest that coughing exerts a major depressant effect on motor activity via a loop that possibly includes cardiopulmonary receptors and inhibitory supraspinal descending pathways.
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PMID:Depressive effect of coughing on spinal monosynaptic reflexes in conscious man. 685 19

The metabolic effects of intraperitoneal administration of promethazine on normoxic, hypoxemic and hypoxemic-oligemic rat brain were assessed by measurement of the cerebral contents of energy phosphates, and selected glycolytic-citric acid cycle intermediates. In normoxic brain promethazine (25-100 mg/kg-1) was associated with unaltered adenylates, increased glucose and aspartate and decreased pyruvate, lactate and malate; a pattern which was compatible with cerebral metabolic depression. Hypoxemic animals receiving either saline or promethazine (25 mg/kg-1) showed equivalent decreases in ATP and increases in lactate which indicated that promethazine had no significant effect on the metabolism of the acutely hypoxic brain. In animals exposed to hypoxemia plus right carotid artery occlusion (oligemia) the promethazine treated group (25 mg/kg-1) showed significantly lower ATP and higher AMP contents which suggested an adverse effect on the metabolism of the acutely hypoxic-oligemic brain. It is concluded that promethazine does not beneficially alter the energy metabolism of the acutely hypoxic or hypoxic-oligemic brain.
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PMID:Effects of promethazine on the energy metabolism of normoxic and hypoxic rat brain. 710 46

The effects of intravenous administration of 50-400 mg/kg imidazole-4-acetic acid (IMA) on the carbohydrate metabolism of the rat brain were assessed by measurement of the cerebral hemisphere contents of energy phosphates and glycolytic--citric acid cycle metabolites. IMA (100-400 mg/kg) produced a spectrum of electroencephalographic (EEG) change ranging from desynchronization to electrical suppression which was associated with unchanged tissue contents of ATP, ADP, and AMP, increasing levels of phosphocreatine, glucose, and aspartate, and decreasing levels of pyruvate, lactate, alpha-ketoglutarate, and malate. The changes in glycolytic intermediates were present within 5 min of injecting IMA (200 mg/kg) and the pattern suggested a suppression of glycolysis. The EEG stage of electrical suppression with episodic spiking (400 mg/kg) was associated with a 30% reduction of cortical high-energy phosphate use. The lowest dose of IMA (50 mg/kg) resulted in episodic EEG desynchronization which was associated with no significant changes of the measured metabolites. The results indicate that IMA is associated with metabolite changes that are compatible with a state of cerebral depression and that the desynchronous EEG pattern is without a biochemical correlate of increased neuronal activity.
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PMID:The effects of imidazole-4-acetic acid on cerebral carbohydrate metabolism. 716 56

The metabolic effects of intravenous administration of 200 mg/kg imidazole-4-acetic acid (IMA) on normoxic, hypoxemic and hypoxemic-oligemic rat brain were assessed by measurement of the cerebral contents of energy phosphates and selected glycolytic-citric acid cycle intermediates. In normoxic brain IMA was associated with unaltered adenylates, increased glucose and aspartate, and decreased pyruvate, lactate, citrate, alpha-ketoglutarate and malate; a pattern which is compatible with cerebral metabolic depression. In hypoxemic brain IMA was associated with a lower accumulation of lactate and a higher level of tissue glucose; again conforming to patterns documented for classical cerebral depressants. In hypoxemic-oligemic brain IMA was associated with a gross deterioration of the tissue ATP content and with a massive lactacidosis which indicated a detrimental action in this hypoxic state.
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PMID:The effects of imidazole-4-acetic acid upon the energy metabolism of normoxic and hypoxic rat brain. 718 30

The cerebral metabolic effects of intravenous administration of 1000 mg/kg gamma-hydroxybutyrate (GHB) were studied by sequential measurement of the cerebral contents of selected glycolytic-citric acid cycle intermediates and energy phosphates in lightly anesthetized rats. The initial change in the glycolytic pathway occurred by 2.5 min, with increases of tissue glucose-6-phosphate and decreases of fructose-1,6- diphosphate which indicated an inhibition of phosphofructokinase. This pattern was transient and was replaced at 5--15 min by increasing tissue glucose and decreasing glucose-6-phosphate which indicated an inhibition of hexokinase. The initial inhibition of phosphofructokinase was associated with functional depression, an isoelectric EEG and an increase of the tissue phosphocreatine which suggested that the observed metabolic pattern was an adaptation to the reduced energy needs of neuronal depression. Within 2.5 min of GHB injection tissue alpha-ketoglutarate and aspartate showed significant increases which suggested a shift in the aspartate aminotransferase reaction. Preliminary calculations indicated that the probable cause of this shift was an increase in oxaloacetate content due to GHB oxidation. The cytoplasmic NADH/NAD+ ratio remained unchanged throughout the entire exposure to GHB (2.5--180 min) and thus gave no support for the hypothesis that GHB interfers with glycolysis via the restriction of free cytoplasmic NAD+ required for the glyceraldehyde phosphate dehydrogenase step.
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PMID:Sequential alterations of cerebral carbohydrate metabolism associated with gamma-hydroxybutyrate. 735 98


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