Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dihydroergocristine (DEC, CAS 17479-19-5) is a dihydrogenated ergot alkaloid with a potent dopaminergic activity that has been proved both in vitro and in vivo. Apart from its effect on the secretion of pituitary hormones, the following actions have been evidenced. It induces stereotyped behaviour and changes in the sleep-waking cycle, and reduces hypoxia-induced cerebral metabolic changes and emesis. The effect of DHEC on behaviour patterns has been studied in aged male rats in comparison with young animals. The acquisition of the active avoidance response in the shuttle-box test and the retention of the passive avoidance response in a step-through passive avoidance task were facilitated in aged rats by an acute treatment with DHEC. The effect on the acquisition and extinction of the pole-jumping performance after a single injection of DHEC at the beginning of the acquisition session was restricted to the first acquisition trial. A more potent effect on the acquisition of the shuttle-box response and on the retention of passive avoidance reaction was found in animals treated subchronically with DHEC. The latter animals also showed a facilitation of acquisition and an inhibition of extinction of the pole-jumping performance. In other experiments, the repeated administration of DHEC was followed by a decrease in the excessive grooming in aged rats, which is considered a sign of the lack of adaptability of these animals. A facilitation of the compensatory mechanisms in experimental models of vertigo has also been found in animals treated with DHEC.
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PMID:[Cerebral actions of dihydroergocristine]. 149 58

Acute oral toxicity of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4- methyl-1-piperazinyl)-7-oxo-7H-pyrido [1,2,3-de][1,4]benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), a new quinolone antibacterial agent, was studied in ddy mice, SD rats and cynomolgus monkeys. LD50 values were 1,881 mg/kg for males and 1,803 mg/kg for females in mice, 1,478 mg/kg for males and 1,507 mg/kg for females in rats and more than 250 mg/kg in females monkeys. Toxic signs included the decrease in locomotor activity, ptosis, tremor, tonic convulsion and respiratory depressed in rodents and soft feces or vomiting in monkeys. At necropsy, no treatment-related changes were observed in any species except for the enlargement of the cecum in rats.
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PMID:Acute oral toxicity of the new quinolone antibacterial agent levofloxacin in mice, rats and monkeys. 162 33

Chronic intravenous toxicity studies in monkeys were carried out with 3-[(2,3-cyclopenteno-1-pyridinium)-methyl]-7-[2-syn-methoximino - 2-(2-aminothiazol-4-yl)-acetamido]-ceph-3-em-4-carboxylate (cefpirome, HR 810; CAS 84957-29-9) a new cephalosporin derivative. In a 90-day study in rhesus monkeys (4 males/4 females per group) dosages of 0, 50, 160 and 500 mg/kg/day were administered. In a 6-month study 5 groups of 6 male and 6 female cynomolgus monkeys received NaCl-solution (0.9%), the vehicle, and 50, 200 or 800/400 mg/kg/d (the highest dosage had to be lowered after the first week due to acute drug intolerance). For clarification of the dose relationship to the findings in the 800/400 mg/kg group, a supplementary 6-month study with 500 mg/kg cefpirome including a vehicle control was also performed. 50 mg cefpirome/kg/d was well tolerated; so too were 160 and 200 mg/kg apart from a slight beta 2-microglobulinuria and/or enzymuria. Almost exclusively at the high dosages retching and vomiting, and exclusively at the high dosages diarrhea, inappetence and physical weakness were sporadically seen in the first phase of the studies. 500 and 400 mg/kg led to increasing signs of discrete renal tubular changes (enzymuria, beta 2-microglobulinuria, cylindruria and minimal histological changes in 2 animals of the 400 mg/kg group). In one rhesus monkey (500 mg/kg) and two cynomolgus monkeys (800 mg/kg) severe kidney damage had developed within the first week. In all dosage groups of the 90-day study special histological methods revealed a dose-dependent increase and enlargement of lysosomes in the epithelia of the proximal renal tubules. Increased cytolysis was, however, not observed. In all the studies there was a dose-dependent increase in the kidney weights of the intermediate and highest dosage groups. The females of the 400 mg/kg group showed slight anemia accompanied by a slight increase in the reticulocyte count. One animal of this group died prematurely probably due to pulmonary embolism. The signs of slight renal impairment including lysosome enlargement, and the slight anemia proved to be reversible.
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PMID:Chronic intravenous toxicity of the new antibiotic cefpirome in monkeys. 198 10

One hour after suicidal ingestion of about 20 mL of a 38% solution of bromofosmethyl, CAS: 2104-96-3 (bromophos), a 52 year-old female was admitted to the hospital with extreme miosis, hypersalivation, hyperperistalsis and muscular fibrillation. Gastric lavage was performed and activated charcoal administered. Cholinergic symptoms were antagonized by repeated doses of 0.5 mg atropine. Because of the high dose of bromophos, hemoperfusion was performed with amberlite XAD4. The bromophos clearance during hemoperfusion was 95 mL/min (flow 200 mL/min). The patient received two doses of 500 mg obidoxime for recurrent muscular fibrillation. The further clinical course was uneventful. On day 4, the patient was transferred to a psychiatric ward because of persistent suicidality. In contrast to poisoning by most organophosphates, red blood cell acetyl cholinesterase was only minimally depressed but the plasma butyryl cholinesterase was initially decreased and normalized within a few days. The records of 25 patients reported to our Poison Control Center with ingestion of more than 1 g bromophos were also evaluated. The most frequent symptoms were miosis, hyperperistalsis, hypersalivation, agitation, nausea/vomiting and convulsions. Nine of the patients had no symptoms. Bromophos is relatively less toxic than its phosphate derivative, parathion.
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PMID:Acute poisoning with bromofosmethyl (bromophos). 205 7

The trial randomly assigned 652 patients with non-ulcer dyspepsia (NUD), defined as chronic or recurrent complaints of acid-related (heartburn, acid regurgitation, epigastric pain) and non-acid related (fullness/vomiting, nausea) symptoms and with no evidence of organic disease, to treatment for 4 weeks with 150 mg of ranitidine (Zantic, CAS 66357-59-3) twice a day, or placebo, according to a double-blind design. The presence and duration of all dyspeptic symptoms were recorded by interviews at the beginning and after 2 and 4 weeks of treatment as well as by diaries. The complete disappearance of all dyspeptic symptoms after 4 weeks in the placebo group was 36%; ranitidine treatment resulted in a significant improvement after 4 weeks (p < 0.05). The effect of ranitidine was slightly more pronounced in acid-related than in non-acid-related symptoms. We conclude that suppression of gastric acid secretion is of clinical value in NUD patients, especially in those suffering from epigastric pain, acid regurgitation and heartburn.
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PMID:Ranitidine in the treatment of non-ulcer dyspepsia. A placebo-controlled study in the Federal Republic of Germany. 781 86

The activity of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) was studied vs. placebo in a double-blind, randomized, multicentre trial, involving 60 pediatric patients with recurrent urinary tract infections. Recovery from acute events was quicker with pidotimod than with placebo (9.6 vs. 12.3 days). In treated patients antibiotic therapy was shorter (6.9 vs. 8.3 days) and main symptomatic parameters (body temperature, vesical tenesmus, stranguria, pollakiuria, total number of symptoms, total symptomatic intensity, rate of asymptomatic patients, haematuria, leukocyturia, positive urinary culture) receded quickly. In patients receiving the drug as well as in patients treated with placebo changes in laboratory parameters were observed, indicating recovery from the acute infectious disease. A significant trend to normalization of the immune response, expressed by chemotaxis and index of leukocyte phagocytosis, was found only in patients treated with pidotimod. After the acute episode a significant decrease of risk of relapses (69%) was observed in these patients. If a relapse occurs, the response of treated patients is quicker (duration of fever, total time of relapses) than for control patients. These findings allow to correlate the individual immune response activation to the resistance to recurrent infections and also to a better response to therapy if the disease occurs and becomes clinically relevant. No side effects were observed. Mild reactions (4 nausea/vomiting, 1 erythema) occurred only in 5 patients (2 pidotimod, 3 placebo) but were attributed to concomitant antibiotic therapy. No alterations of main laboratory parameters were found. These findings confirm the tolerability of the drug also in long-term treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapeutic efficacy and safety of pidotimod in the treatment of urinary tract infections in children. 785 49

A preliminary dose-range finding study, two 13-week studies and a 52-week study were performed in beagle dogs with polaprezinc (catena-(S)-[mu-[Na-(3-aminopropionyl)histidinato (2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7, Z-103), a novel anti-peptic ulcer agent, as part of a safety evaluation program. In the preliminary single-dose study, treatment-related findings were confined to one animal treated with 200 mg/kg and consisted in emesis and mucosal lesions in the stomach and upper small intestine. Based on these data, dosages were selected for the main 13-week study (0, 50, 120 and 300 mg/kg/day) and additional 13-week study (0, 8 and 20 mg/kg/day). The dosages for the 52-week study were 8, 20 and 50 mg/kg/day. In the 13-week studies, dosages of 50 mg/kg/day and above resulted in emesis, mild diarrhea and salivation; reduced food consumption and associated reduction in body weight gain for high dosed females; increased blood alkaline phosphatase and decreased urinary specific gravity; histopathological changes in the kidney of the high dosed group in males and females. These changes were no longer apparent following the withdrawal period. In the 52-week study, similar but milder and transient results were noted at the high dose of 50 mg/kg/day. From these results, the no-effect dose level was estimated to be 20 mg/kg b.w./day.
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PMID:Toxicity of the novel anti-peptic ulcer agent polaprezinc in beagle dogs. 789 70

Pergolide (LY127809, CAS 66104-23-2), a dopamine agonist for the treatment of Parkinson's disease, was evaluated for toxicity in acute, subchronic, and chronic studies. Acute toxicity tests using oral, intravenous and intraperitoneal routes were conducted in rats, mice, rabbits, and dogs. The acute oral median lethal doses (MLD) ranged from 8.4 to 33.6 mg/kg in Wistar and Fischer 344 rats, and from 54.0 to 87.2 mg/kg in ICR mice. Oral doses of 20 and 25 mg/kg produced no mortality in rabbits or dogs, respectively. The MLD by the iv route ranged from 0.59 to 0.87 mg/kg for Fischer 344 rats and from 11.6 to 37.1 mg/kg for ICR mice. The predominant signs of toxicity in the acute studies included hyperactivity, poor grooming, ptosis, aggressive behavior, increased gnawing activity, tremors, convulsions, and emesis. In the subchronic and chronic studies, Fischer 344 rats, B6C3F1 mice, and beagle dogs were administered pergolide either by gavage or in the diet for up to 1 year. Daily doses in these studies ranged up to 20 mg/kg for rats, 45 mg/kg for mice, and 5 mg/kg for dogs. The predominant treatment-related effects seen in these studies were attributable to the pharmacologic activity of pergolide. These consisted primarily of CNS-mediated clinical signs in rats and dogs, weight loss or decreased weight gain, emesis in dogs, and inhibition of lysis of corpora lutea with a corresponding increase in the weight of the uterus and ovaries. Pergolide treatment was not associated with any specific target organ toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preclinical toxicology studies with the new dopamine agonist pergolide. Acute, subchronic, and chronic evaluations. 819 91

The pharmacokinetic and pharmacodynamic effects of co-administration of flosequinan (BTS 49465, CAS 76568-02-0) and digoxin (CAS 20830-75-5) were investigated in 12 healthy volunteers. A 4-day, open, lead-in phase established the pharmacokinetics of flosequinan (100 mg on the first day and 50 mg for the next 3 days) and was followed by a 24-day open interaction phase. Digoxin was administered alone (0.75 mg for the first 3 days and 0.5 mg for the next 4 days) to establish steady-state pharmacokinetics and in combination with flosequinan (100 mg on the 8th day and 50 mg for the next 14 days with 0.5 mg digoxin daily), and finally digoxin alone (0.5 mg for the remaining 3 days). No statistically significant differences were observed for any of the pharmacokinetic parameters for flosequinan, its major metabolite BTS 53554, or digoxin when flosequinan and digoxin were administered alone or concomitantly, but the confidence intervals for differences were relatively wide. Overall diastolic blood pressure was significantly lowered by 10% with concomitant treatment compared with flosequinan monotherapy. There were no significant effects on overall heart rate or systolic blood pressure, although pre-dose heart rate was increased by 6% during concomitant administration compared with digoxin alone, and remained high and digoxin alone. Adverse events (headache, nausea and vomiting) were reported by 2 volunteers on digoxin and 5 on concomitant therapy. One volunteer was withdrawn during concomitant therapy because of severe headache and vomiting. The results from this study indicate that no pharmacokinetic interaction occurred during concomitant administration of flosequinan and digoxin in healthy volunteers.
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PMID:Effects of concurrent administration of flosequinan and digoxin on the pharmacokinetics of each drug. 819 94

The pharmacological effects of the metabolites M1 and M2 of mosapride citrate ((+/-)-4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholi nyl] methyl]benzamide citrate, AS-4370, CAS 112885-42-4), a gastroprokinetic agent with serotonin 5-HT4 receptor agonist property, were compared with those of mosapride. In isolated guinea-pig ileum treated with phenoxybenzamine, the metabolites M1 and M2 enhanced electrically-evoked contractions with EC50 values of 1.2 x 10(-7) mol/l and 1.0 x 10(-6) mol/l, respectively. The metabolite M1 was twice less potent than that of mosapride. When administered intravenously, the metabolite M1 enhanced gastric emptying of a semisolid meal in mice and rats; the potency was 3 times less than that of mosapride in mice and almost equal to that of mosapride in rats. When administered orally, the metabolite M1 enhanced gastric emptying of a semisolid meal in mice and rats, and also enhanced gastric emptying of a resin pellet meal in rats. The potency of metabolite M1 was 10 times less than that of mosapride in rats, although it was equal to that of mosapride in mice. In these experiments, the metabolite M2 was far less active. In addition to these gastroprokinetic properties, the metabolite M1 possessed a potent 5-HT3 receptor antagonist property. The metabolite M1 antagonized the 2-methyl-5-HT-induced bradycardia in anesthetized rats with an ED50 value of 10.5 micrograms/kg, i.v., and inhibited the cisplatin-induced emesis in ferrets with a potency approximately 25 times that of mosapride. These results suggest that the metabolites M1 and M2 of mosapride do not play a crucial role in the gastroprokinetic effect of mosapride.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological effects of the new gastroprokinetic agent mosapride citrate and its metabolites in experimental animals. 826 74


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