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)

Carbromal is metabolized extensively in humans. The major metabolites known to date are bromoethylbutyramide, ethylbutyrylurea and inorganic bromide. After ingestion of a therapeutic dose of 1.0 g carbromal (4.2 mmoles) by four healthy volunteers highest concentrations in serum were found to be for carbromal 30 mumoles/l, for bromoethylbutyramide up to 20 mumoles/l and for ethylbutyrylurea 2--3 mumoles/l. In patients acutely poisoned by carbromal-containing sedatives serum concentrations measured were in the range of 200 mumoles/l carbromal, 350 mumoles/l bromoethylbutyramide and 50 mumoles/l ethylbutyrylurea. These patients were comatose, apneic, had isoelectric encephalographic records and decreased body temperature. The degree of central nervous depression as judged by clinical signs was found to correlate with the serum concentrations of carbromal and of bromoethylbutyramide. Pharmacological activity and acute toxicity of carbromal and its two metabolites were examined in rats and compared with the activity of phenobarbitone. For intraperitoneal injection LD-50 values were found to be for carbromal 1.8 mmoles/kg, for bromoethylbutyramide 1.5 mmoles/kg, for ethylbutyrylurea 5.0 mmoles/kg and for phenobarbitone 0.9 mmoles/kg. Carbromal and bromoethylbutyramide severely decreased body temperature. The relative narcotic activity was estimated to be for carbromal = 100; bromoethylbutyramide = 66; ethylbutyrylurea = 33; phenobarbitone = 100. The anticonvulsive activity against pentetrazol-induced generalized seizures was nearly identical for carbromal, bromoethylbutyramide and phenobarbitone. Anticonvulsant activity of ethylbutyrylurea was two to three times less than that of carbromal. Inorganic bromide was found to increase the narcotic activity of carbromal and of bromoethylbutyramide. The findings show that the clinical signs of central nervous system depression seen in patients acutely poisoned with carbromal are caused mainly by unchanged carbromal and by its metabolite bromoethylbutyramide.
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PMID:[On the toxicology of carbromal. III. Role of active metabolites in humans acutely poisoned with carbromal-containing sedatives (author's transl)]. 2 10

An anaesthetic technique comprising a combination of phenoperidine (0.1 mg . kg-1), diazepam (0.06 mg . kg-1) and pancuronium bromide (0.1 mg . kg-1) with controlled ventilation was evaluated in 12 patients with severe coronary artery disease. The heart rate, cardiac output and mean arterial blood pressure did not change significantly between the preinduction and postinduction measurements. The right atrial pressure and pulmonary capillary wedge pressure decreased significantly by 33% and 36%, respectively, probably due to the influence of positive-pressure ventilation. There was no depression of the left ventricular performance.
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PMID:Cardiovascular effects of neurolept anaesthesia in patients with coronary artery disease. 4 52

Intraoperative hypertension is a common problem in patients undergoing myocardial revascularization. Twenty patients who developed acute hypertension after sternotomy were studied. Ten patients received three doses of intravenous nitroglycerin (32, 64, and 96 mcg. per minute), and 10 patients received nitroprusside, (20, 40, and 60 mcg. per minute). All patients were anesthetized with morphine, diazepam, nitrous oxide, oxygen, and pancuronium bromide. Five patients in each group also received enflurane. The study compared the effects of nitroglycerin and nitroprusside on systemic hemodynamics, myocardial oxygen supply/demand relationships, and ischemic changes on the electrocardiogram. Both drugs decreased preload and afterload in a dose-related manner. Heart rate increased significantly only with the largest dose of each drug. Myocardial oxygen demand was decreased significantly by both drugs, while the coronary perfusion pressure was decreased more by nitroprusside. Both nitroglycerin and nitroprusside improved left ventricular performance. Nitroglycerin improved ST-segment depression in eight of 10 patients; while nitroprusside improved the ST segments in six patients, and worsened the ST segments in three patients. None of the nitroglycerin group had worsening of the electrocardiographic ST segments. These findings demonstrate that both drugs can control intraoperative hypertension and can decrease myocardial oxygen demand. Nitroglycerin was shown to improve ischemic changes on the electrocardiogram more often than nitroprusside.
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PMID:Vasodilator therapy during coronary artery surgery. Comparison of nitroglycerin and nitroprusside. 10 11

The intercalating dye ethidium bromide (EB), inhibits excision of pyrimidine dimers from UV-irradiated excision-proficient Escherichia coli B/r hcr+ cells. Inhibition is total at a 2.5 - 10(-4) M concentration 120 min after irradiation with a dose of 750 erg/mm2. The viability of irradiated cells diminishes in proportion to the EB concentration. Under wholly analogous conditions of cultivation and irradiation no inhibitory effect of KCN and caffeine (CFF) and only a slight effect of chloramphenicol (CAP) on dimer excision has been observed. The viability of cells is affected by these compounds but it does not appear to depend on the quantity of excised photoproducts. A change in the secondary structure of DNA induced by intercalation of EB appears to be the reason for the depression of excision of UV photoproducts.
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PMID:Effect of some drugs on excision repair in E. coli cells. 32 80

The effect of tetraethylammonium (TEA) bromide on the neurally and iontophoretically evoked endplate current (EPC) of frog sartorius muscle was investigated using voltage-clamp and noise analysis techniques, and its binding to the acetylcholine (ACh) receptor ionic channel complex was determined on the electric organ of Torpedo ocellata. TEA (250-500 microM) produced an initial enhancement followed by a slow decline in the amplitude of the endplate potential and EPC, but caused only depression in the amplitude of the miniature endplate potential and current. In normal ringer's solution, the EPC current-voltage relationship was approximately linear, and the decay phase varied exponentially with membrane potential. Upon addition of 50-100 microM TEA, the current-voltage relationship became markedly nonlinear at hyperpolarized command potentials, and with 250-2000 microM TEA, there was an initial linear segment, an intermediate nonlinear segment, and a region of negative conductance. The onset of nonlinearity was dose-dependent, undergoing a 50 mV shift for a 10-fold increase in TEA concentration. The EPC decay phase was shortened by TEA at hyperpolarized but not depolarized potentials, and remained a single expotential function of time at all concentrations and membrane potentials examined. These actions of TEA were found to be independent of the sequence of polarizations, the length of the conditioning pulse, and the level of the initial holding potential. TEA shifted the power spectrum of ACh noise to higher frequencies and produced a significant depression of single channel conductance. The shortening in the mean channel lifetime agreed closely with the decrease in the EPC decay time constant. At the concentrations tested, TEA did not alter the EPC reversal potential, nor the resting membrane potential, and had little effect on the action potential duration. TEA inhibited the binding of both [3H] ACh (Ki = 200 microM) and [3H]perhydrohistrionicotoxin (Ki = 280 microM) to receptor-rich membranes from the electric organ of Torpedo ocellata, and inhibited the carbamylcholine-activated 22Na+ efflux from these microsacs. It is suggested that TEA reacts with the nicotinic ACh-receptor as well as its ion channel; the voltage-dependent actions are associated with blockade of the ion channel. The results are compatible with a kinetic model in which TEA first binds to the closed conformation of the receptor-ionicchannel complex to produce a voltage-depdndent depression of endplate conductance and sudsequently to its open conformation, giving rise to the shortening in the EPC decay and mean channel lifetime.
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PMID:Reaction of tetraethylammonium with the open and closed conformations of the acetylcholine receptor ionic channel complex. 48 41

A peptide having the reputed essential amino acid sequence to show cataglykin-like effects was prepared from human growth hormone (hGH) by cyanogen bromide cleavage and was tested in two systems in which cataglykin has effects. The peptide prolonged the depression of blood glucose concentration brought about by insulin during intravenous insulin tolerance tests in rats. However, the magnitude of the depression caused by insulin was not increased. There was no stimulation by the peptide of glucose uptake by rat hemidiaphragrams in the presence of insulin in vitro. Thus, this peptide does not duplicate the effects of cataglykin.
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PMID:Tests for cataglykin activity on a cyanogen bromide fragment of human growth hormone. 61 23

1. Responses of single cells in the isolated cat spinal ganglion to GABA applied by superfusion or by iontophoresis were recorded using intracellular micro-electrodes. 2. Of the twelve structurally related compounds investigated, GABA was the most effective in its ability to produce a depolarization of the cell membrane. 3. Studies determining concentration-response relationships indicate that two to three molecules of GABA are required to combine with the GABA receptor for activation. 4. Bicuculline and picrotoxin, each act in a non-competitive manner to antagonize the GABA-induced membrane current. 5. The equilibrium potential for iontophoretically induced GABA depolarizations (EGABA) was found to be -23.5 plus or minys 6.1 mV. EGABA was independent upon [cl-]o, but independent of [Na+]o, [K+], or [Ca2+]o. 6. Intracellular injection of twenty antions (Br-, I-, NO2-, NO3-, ClO4-, SCN-, Bf4-, HS-, OCN-, ClO3-, BrO3-, F-, HCO2-, HSO3-, HCO3-, CH3CO2-, SO42-, C6H5O73-) indicated that the activated GABA receptor membrane was permeable to those anions whose hydrated diameter is no larger than that of ClO-3. 7. Restoration of the GABA depolarization to its control level after augmentation by Cl- injection had a mean time constant of 27.8 plus or minus 2.6 min. Picrotoxin did not alter this value. 8. When foreign anions were exchanged for Cl- in the perfusion solution, the ten anaions smaller or equal to ClO3-, decreased the GABA depolarization by 50-90% and increased its time course 1.5-2.0 x control. The only exception having a small radius was Br- which augmented the amplitude 10-30%. 9. The ten anions larger than ClO3- produced a biphasic effect, i.e. an initial augmentation followed by a marked (up to 100%) depression of the response. Experiments with CH3COO-, CH3SO4-, or HOCH2CH2SO3-, indicated that this depression was non-competitive.
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PMID:Characterization and ionic basis of GABA-induced depolarizations recorded in vitro from cat primary afferent neurones. 63 14

The hypothermic response following intraperitoneal doses (6.25, 12.5, and 25 mg/kg) of cobaltous chloride was investigated in Swiss albino mice. The magnitude and duration of rectal temperature depression were dose related. In each case, maximal hypothermia was evident within 30 min after injection. Body temperature depression was noted 30 min after oral, subcutaneous, intraperitoneal, intravenous, and intracerebral administration of cobaltous chloride. Cobalt was most active when administered intracerebrally, suggesting a central component to the thermolytic response. Rectal temperature depression following cobaltous chloride was dependent on the ambient temperature. The time course of the effect of cobaltous chloride on rectal and cutaneous tail temperature was noted. Cutaneous tail temperature depression occurred throughout the rectal temperature response, suggesting that cobalt may decrease heat production. Pretreatment with atropine sulfate, hexamethonium bromide, or nicotine failed to modify the temperature response to cobalt. Chlorpromazine hydrochloride pretreatment resulted in a partial antagonism of cobalt-induced hypothermia, presumably through a mechanism other than cholinergic blockade.
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PMID:Cobaltous choride-induced hypothermia in mice I: effect of pretreatment with anticholinergic drugs. 66 Apr 60

The electrocardiogram was monitored in 100 patients undergoing oesphago-gastro-duodenoscopy. Premedication differed: 25 patients each were given either (Group I) atropine 0.5 mg, hyoscine-N-butylbromide 20 mg, and diazepam 5 mg, or (Group II) hyoscine-N-butyl-bromide 20 mg and diazepam 5 mg, or (Group II) diazepam 5 mg and glucagon 0.2 mg, or (Group IV) only diazepam 5 mg intravenously. After injection of the parasympatholytic drugs (Groups I and II) there was a significantly higher heart rate duringthe entire length of the examination than in groups III and IV. Nine of the ten cases of ascending S-T depression were found in Groups I and II, while descending (ischaemic) S-T changes occurred equally frequently in patients of all four groups. Two of the three more serious arrhythmias were registered after atropine. Since parasympatholytic drugs fail to inhibit arrhythmias and ST-T changes, while accentuating the rise in heart rate, it is recommended that premedication for oesophago-gastro-duodenoscopy should not include such drugs.
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PMID:[Cardiac side-effects of oesophago-gastro-duodenoscopy in relation to premedication (author's transl)]. 68 92

Single nuclear gene inheritance was shown to be responsible for increased resistance to: eight diverse inhibitors of mitochondrial function (antimycin, carbonylcyanide-m-chlorophenylhydrazone, chloramphenicol, oligomycin, tetracycline, triethyltin bromide, triphenylmethylphosphonium bromide and triton-X-165); and an inhibitor of cytoplasmic protein synthesis (cycloheximide). Continuous monitoring of oxygen uptake during respiratory adaptation showed that anerobic pretreatment of resistant cells sensitized respiratory adaptation to chloramphenicol and antimycin. However, since a depression of mitochondrial function by catabolite repression did not result in sensitization to antimycin, alteration of the mitochondrial membrane does not appear to be responsible for resistance to mitochondrial inhibition. Alteration of cellular binding sites was not responsible for resistance since in vitro mitochondrial protein synthesis was sensitive to chloramphenicol and in vitro mitochondrial respiration was sensitive to oligomycin, carbonylcyanide-m-chlorophenylhydrazone, and antimycin. Autoradiography of an ethylacetate-ethanol extract of [14C]chloramphenicol-treated resistant cells indicated that resistance was not due to enzymatic modification of inhibitors. The maintenance of an antimycin-resistant respiration by protoplasts of resistant cells ruled out the involvement of the cell wall in cellular resistance. The reduced transport of [14C]chloramphenicol by resistant cells (1% of normal cells) indicated that a single nuclear gene mutation can alter the permeability of the plasma membrane to many diverse inhibitors.
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PMID:Reduced plasma membrane permeability in a multiple cross-resistant strain of Saccharomyces cerevisiae. 109 46


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