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)

A probably promoter-specific decrease of L-type pyruvate kinase (L-PK) in Wistar rat liver is described. The possibility of utilizing the decrease in L-PK activity for screening of hepatic promoters is discussed. A significantly decreased level of activity of L-PK was observed during continuous feedings of the hepatocarcinogen 3'-methyl-4-dimethylaminoazobenzene [(3'-MeDAB) CAS: 55-80-1], which initiates and promotes hepatocarcinogenesis, and of the known hepatic promoters phenobarbital [(PB) CAS: 50-06-6] and dichlorodiphenyltrichloroethane (CAS: 50-29-3) for at least 4 weeks. In contrast, if it occurred, the decrease in L-PK activity by the nonpromoting agents amobarbital (CAS: 57-43-2) and diphenylhydantoin. (CAS: 57-41-0) was temporary and almost overcome by the 4th week. The depression of L-PK activity caused by PB was reversible, was inversely correlated with PB concentration in the diet, and seemed to be organ-specific. Although hepatic promoters lowered L-PK activity in this study, data are so limited that a much more extensive study is necessary before a general conclusion can be drawn. In contrast to L-PK activity, the activity of K-type pyruvate kinase (K-PK) was induced by injections of the carcinogen diethylnitrosamine (CAS: 55-18-5) or the hepatotoxin CCl4 (CAS: 56-23-5) or by the feeding of 3'-MeDAB. However, feeding of PB or 2-methyl-4-dimethylaminoazobenzene (CAS: 54-88-6), which initiates but does not promote hepatocarcinogenesis, did not increase K-PK activity.
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PMID:Decrease in L-type pyruvate kinase activity in rat liver by some promoters of hepatocarcinogenesis. 659 85

The effects of the cardiotonic agent pimobendan (CAS 118428-36-7, UD-CG 115 BS) and its main metabolite UD-CG 212 on dog cardiac myofibrillar calcium responsiveness and ATPase activity were studied at nominal free inorganic phosphate (Pi) and at 5 mmol/l Pi. A rightward shift of the pCa-tension relationship with a marked depression of maximal tension was observed in the presence of 5 mmol/l Pi. Pimobendan increased myofibrillar calcium responsiveness at concentrations > or = 10(-5) mol/l. These effects of pimobendan were significantly greater at 5 mmol/l Pi than at nominally free Pi. UD-CG 212 had no influence on myofibrillar calcium responsiveness at nominally free Pi, however, significant effects were observed at 10(-9) mol/l UD-CG 212 in the presence of 5 mmol/l Pi. UD-CG 212 (10(-8) mol/l) did not influence myofibrillar ATPase activity at pCa's 6.23, 5.99, and 4.36 with or without 5 mmol/l Pi, whereas pimobendan (10(-4) mol/l) had an effect only at pCa = 5.99 (without Pi) and pCa = 4.36 (+ 5 mmol/l Pi). The data suggest that the increase in myofibrillar calcium responsiveness at submaximal calcium concentrations by pimobendan and UD-CG 212 in the presence of 5 mmol/l Pi is brought about by a change in cross-bridge kinetics or by enhancement of thin filament activation by adjacent strong cross-bridges. At maximal calcium activation, pimobendan may additionally increase the population of strong cross-bridges.
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PMID:Effects of pimobendan and its metabolite on myofibrillar calcium responsiveness and ATPase activity in the presence of inorganic phosphate. 771 Apr 34

Pergolide (Permax, LY127809, CAS 66104-23-2) a dopamine agonist for the treatment of Parkinson's disease, was evaluated for reproductive and developmental toxicity. Pergolide was administered in the diet at levels of 0, 5, 15, or 50 ppm to male and female ICR mice. In the F0 generation, the males were treated for 9 weeks prior to mating and throughout mating. The females were treated for 2 weeks prior to mating and throughout mating, gestation, and location (postnatal segment only). Females assigned to the teratology segment were killed on gestation day 18 for evaluation of fetal viability, weights, and morphology. Females assigned to the postnatal component were allowed to deliver and maintain their offspring throughout a 21-day lactation period. One male and one female were selected from each litter to continue as the F1 generation. Possible exposure of the F1 generation to pergolide ended at weaning. Growth of the F1 animals was monitored and reproductive performance evaluated. Treatment-related effects in the F0 generation were consistent with the pharmacologic effects of a dopamine agonist. These effects included pregnancy blockage at the 50-ppm dietary level and dose-related body weight depression in lactating dams and suckling progeny at the 15- and 50-ppm dietary levels. An increase in progeny mortality at the 50-ppm dietary level was attributed to lactation failure of the treated dams. The F1 mice of the 15- and 50-ppm groups remained smaller than the control mice until termination at approximately 20 weeks of age, although weight gains following weaning were not depressed and no impairment of mating performance or fertility was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reproductive and developmental toxicity of the dopamine agonist pergolide mesylate in mice. 784 27

The intravenous administration of endotoxin to anesthetized rats resulted in different hypotensive reactions depending on its dosage. More than 10 mg/kg of endotoxin induced biphasic hypotension; the first phase consisted in a small and transient depression (approximately 15 mmHg) of mean arterial pressure occurred within 1 min after the administration, and the second phase was a large and sustained depression (maximally 40 mmHg) observed from 1 h after the injection. At less than 3 mg/kg of endotoxin, the first phase of hypotension did not occur whereas the second phase of hypotension was observed. Pre-treatment or post-treatment with a specific platelet activating factor (PAF) antagonist, SM-12502 ((+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl, CAS 119383-00-5) inhibited the second phase of endotoxin (1 mg/kg)-induced hypotension. In addition, post-treatment with another PAF antagonist, (3-(4-(2-chlorophenyl)-9-methyl-6H-thieno (3,2-f) (1, 2,4)-thiazolo-phenone) also inhibited the second phase of hypotension. Blood PAF-like substance level, measured by the PAF radioimmunoassay, slightly increased at 1 min after administration of endotoxin (30 mg/kg). At 90 min after the injection, endotoxin (1 mg/kg) induced a significant increase of PAF-like substance level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of the platelet activating factor antagonist (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride on endotoxin-induced hypotension and hematological parameters in rats. 784 33

Single oral dose toxicity of nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo- 1-pyrrolidinyl) acetamide, DM-9384, CAS 77191-36-7), a new cognition-enhancing agent, was examined in ddY mice, SD rats and beagle dogs. The LD50 values of nefiracetam were 2005 mg/kg for male mice and 1940 mg/kg for female mice, 1182 mg/kg for male rats and 1408 mg/kg for female rats and more than 500 mg/kg for beagle dogs. Common toxic signs in all species were a decrease in locomotor activity, lying on the side or back and loss of righting reflex, considered to be caused by depression of the central nervous system. Pathologically, no remarkable change associated with nefiracetam administration was observed in any species. In addition, toxicities of the decomposition product (D-2) and by-products (Bis, 3-Me and 4-Me) of nefiracetam were examined by oral administration, and of the metabolites (M-3 and M-11) by intravenous injection in male ddY mice. LD50 values of the 3-Me and 4-Me forms were 1399 and 1534 mg/kg, respectively. Clinical signs in mice treated with these by-products were similar to those caused by nefiracetam. The other compounds induced no toxic signs or death up to the highest dose (2000 mg/kg) used.
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PMID:Single dose toxicity study of the new cognition-enhancing agent nefiracetam in mice, rats and dogs. 801 91

The effects of the new dihydropyridine Ca-antagonist felodipine (CAS 72509-76-3) (3 x 10(-9) mol/l - 10(-6) mol/l) on intracellular action potentials of the rabbit sinus node and atrium were studied. Results were compared to the effects of nifedipine (10(-8) mol/l - 3 x (-10) mol/l). Additionally, rate-dependent effects of both substances on AV nodal conduction time were assessed. The data demonstrate a concentration-dependent reduction of sinus nodal automaticity due to depression of phase 4 automaticity concomitant with a reduction of the maximum upstroke velocity of the sinus action potential by both substances. Felodipine was about one half order of magnitude more potent than nifedipine. Both substances exerted little effects on action potentials in atrial cells. Felodipine and nifedipine led to a concentration and frequency-dependent ("use-dependent") retardation of AV nodal conduction. Again felodipine was about one half order of magnitude more potent than nifedipine.
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PMID:Effects of dihydropyridine calcium-antagonists on intracellular action potentials of rabbit sinus node, atrium and atrioventricular node. Comparison of felodipine with nifedipine. 805 68

Twenty-two patients suffering from an obsessive and compulsive disorder (OCD) according to DSM-III-R were investigated by polysomnographic sleep EEG recordings under drug-free conditions and compared to age- and sex-matched healthy controls. Sleep efficiency was significantly lower and wake % SPT was significantly increased in the patient group compared to healthy subjects. Sleep architecture did not differ among the two samples. Especially REM sleep measures, in particular, REM latency did not differ among the groups. No positive correlation was found between sleep variables and rating inventories for obsession and compulsions (Y-BOCS), depression (Hamilton) and anxiety (CAS). A secondary depression did not influence sleep EEG variables. The results of this study contradict the assumption that OCD patients show REM sleep and slow wave sleep abnormalities similar to those shown by patients with primary depression.
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PMID:Sleep EEG of patients with obsessive-compulsive disorder. 817 42

The hemodynamic effects of celiprolol (CAS 56980-93-9), a betablocker with beta 1 antagonist and beta 2 agonist properties, were compared with those of atenolol (CAS 29122-68-7) in 12 patients with mild to moderately severe hypertension (diastolic BP 95-110 mmHg). Celiprolol and atenolol lead to a similar and significant reduction of systolic and diastolic blood pressure (p < 0.005). However, with celiprolol heart rate at rest was significantly less depressed then with atenolol (p = 0.004) and showed a distinctly less pronounced depression of heart rate with exercise (p = 0.004). Cardiac output at rest was reduced by 19% under atenolol, but was increased by 9% under celiprolol treatment; in this respect, the two medications differed significantly (p = 0.03). The adaptation of heart rate and cardiac output to exercise was better with celipropol as compared to atenolol treatment. The difference between arm arterial pressure and ankle occlusion pressure at rest was not significantly influenced by atenolol, whereas celiprolol treatment increased this difference by a mean of up to 16 mmHg (p = 0.009). This different effect on peripheral arterial circulation was even more pronounced after exercise. Both celiprolol and atenolol increased blood cell flow velocity in the nailfold capillaries, but this increases was statistically only significant with celiprolol (p = 0.047). These results demonstrate that the hemodynamic effects of celiprolol were significantly different from those of atenolol; celiprolol produces less bradycardia, increases cardiac output at rest and decreases peripheral arterial resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Different hemodynamic effects of celipropol and atenolol in patients with mild to moderate hypertension. 857 24

(S)-10-[(S)-(8-Amino-6-azaspiro[3,4]octan-6-yl)]-9-fluoro-2, 3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxyli c acid hemihydrate (CAS 151390-79-3, DV-7751a) a new quinolone antibacterial agent, was examined for LD50 value, phototoxicity and convulsion inducing potential in laboratory animals. A single oral administration of DV-7751a induced soft stool in rats at 1000 and 2000 mg/ kg and in monkeys at 250 mg/kg and vomiting in monkeys at 500 mg/kg or more. A single intravenous administration caused a decrease in locomotor activity, respiratory depression, convulsion, pulmonary edema and death in rats and mice. The LD50 values with oral administration were more than 2000 mg/ kg for rats and mice and more than 250 mg/kg for monkeys, and those with intravenous administration were 164.3 mg/kg for rats of both sexes at an injection rate of 2 ml/min, 118.8 mg/kg for male rats and 104 to 125 mg/kg for female rats at 0.5 ml/min, and 184.7 mg/kg for male mice and 187.4 mg/kg for female mice. DV-7751a showed very weak phototoxicity in mice after single oral administration of 600 mg/kg, followed by UVA irradiation, but no convulsion after oral administration of 200 or 1000 mg/kg in combination with 4-biphenylacetic acid at 400 mg/kg.
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PMID:LD50 value, phototoxicity and convulsion induction test of the new quinolone antibacterial agent (S)-10-[(S)-(8-amino-6-azaspiro[3,4]octan-6-yl)]-9-fluoro-2, 3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxyl ic acid hemihydrate in laboratory animals. 876 55

Nitroglycerin (glyceryl trinitrate, CAS 55-63-0, NTG) administered with an oral spray may be more effective in relieving anginal pain than sublingual tablets especially when the patient's mouth is dry. In this study, the effect of a NTG oral spray (Myocor Spray) on exercise-induced angina was compared with that of a sublingual tablet in relation to the oral dryness. In 17 patients with effort angina, graded bicycle exercise was performed twice at an interval of one week. Exercise was discontinued upon the onset of moderate anginal pain. Immediately after exercise, the oral dryness was evaluated by touching the tip of the tongue with a blotting paper for a moment. Then, 0.3 mg of NTG was administered by either a squirt of spray or a sublingual tablet in a randomized crossover fashion. Exercise results were reproducible between two exercise tests. According to the extent of the wet area of the blotting paper, the subjects were divided into two groups. In 7 patients of the wet group, the remission times of chest pain and ST segment depression were not significantly different by the formulation of NTG. In 10 patients of the dry group, however, both chest pain and ST depression more rapidly recovered with use of the oral spray (p < 0.05 and p < 0.05, respectively). These results strongly suggest that the NTG oral spray is superior to the sublingual tablet in relieving anginal attacks, when the oral wetness is decreased.
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PMID:Studies on the response of nitroglycerin oral spray compared with sublingual tablets for angina pectoris patients with dry mouth. A multicenter trial. 907 31


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