Gene/Protein Disease Symptom Drug Enzyme Compound
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 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pergolide (LY127809, CAS 66104-23-2), a non-selective dopamine agonist, was evaluated for broad behavioral properties in a wide range of pharmacological tests. The selective dopamine2(D2) agonist, bromocriptine, served as a reference standard for those tests where behavioral activity was noted with pergolide. Pergolide and bromocriptine were administered orally to mice at doses of 0.3-30 and 3-300 mg/kg, respectively. Both compounds produced biphasic effects on spontaneous activity, increased hexobarbital-induced sleep time, and lowered mouse body temperature. Qualitative changes with pergolide were observed with some mice showing hyporeactiveness, ptosis, slowed respiration and placing loss. Reserpine-induced hypothermia was reversed by pergolide with significant increases in the body temperature of reserpine-treated mice. However, a further reduction in the body temperature of reserpinized hypothermic mice was seen following bromocriptine administration. Acetic acid-induced writhing and performance on the rotarod were both impaired by higher doses of pergolide. Bromocriptine administration also reduced writhing at higher doses but did not alter performance on the rotarod. Pergolide had no effect on seizure activity as evaluated by electroshock, pentylenetetrazol (pentetrazol) or strychnine. Oxotremorine-induced tremors and salivation, grip strength, and tail-flick were not affected by pergolide. Neither pergolide nor bromocriptine altered established shuttle-avoidance behavior in rats at oral doses of 0.1 to 30 mg/kg. Behavioral assessment of pergolide in dogs was complicated by severe emetic responses at clinically relevant doses greater than 0.003 mg/kg. In summary, these data suggest that pergolide produces a behavioral profile which is characteristic of dopaminergics.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Behavioral characterization of the new potent nonselective dopamine agonist pergolide. 141 51

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

The putative cognition enhancer linopirdine (3,3-bis(4-pyrindinylmethyl)-1-phenylindolin-2-one, CAS 105431-72-9) is supposed to act by enhancing the release of neurotransmitters, especially acetylcholine. The present study assessed the effects of a single administration of this compound on the central nervous system in eight different rat and mouse models (CNS general pharmacology). In each test performed, linopirdine was administered subcutaneously in doses of 3, 10, and 30 mg/kg. The compound did not affect traction ability and nociceptive responsiveness nor did it induce catalepsy. Linopirdine impaired motor coordination in the balance rod test. The compound showed a distinct proconvulsive action in the pentylenetetrazole threshold dose test and induced in the highest dose tested (30 mg/kg) lethal seizures in some mice. It increased the duration of hexobarbital-induced anaesthesia in mice. Rats treated with linopirdine showed ptosis, salivation, slight sedation, paw beating and slight hypothermia. These results support the hypothesis that linopirdine acts by elevating the release of different neurotransmitters such as acetylcholine and dopamine. The compound has a low potential to produce side effects at pharmacodynamic active doses.
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PMID:General pharmacology of the putative cognition enhancer linopirdine. 777 41

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 general pharmacological properties of a novel cholecystokinin-A antagonist, loxiglumide ((+/-)-4-(3,4-dichlorobenzamido)-N-(3-methoxypropyl)-N-pentylgl utaramic acid, CR 1505, CAS 107097-80-3) on central nervous system, autonomic nervous system, cardio-respiratory system, gastrointestinal system, hematological and miscellaneous systems were investigated in experimental animals. 1. Central nervous system: At a dose of 30 mg/kg, i.v. loxiglumide showed ptosis in one of 6 mice, but at doses of 3 and 10 mg/kg, i.v. no change on gross behavior in mice. Loxiglumide had no effect on locomotor activity and thiopental-induced hypnosis, anti-convulsive activity, analgesic activity in mice and rectal temperature changes in rats. 2. Autonomic nervous system: In vitro, loxiglumide at concentrations of 10(-4) and 3 x 10(-4) mol/l slightly inhibited agonist-induced contractions in the isolated guinea pig ileum and spontaneous rhythmic contractions in the isolated non-pregnant rat uterus. But loxiglumide had no effect on oxytocin-induced contraction in isolated non-pregnant rat uterus. 3. Cardio-respiratory system: Loxiglumide had no effect on heart rate and electrocardiogram in anesthetized dogs. But it slightly increased blood pressure and decreased the frequency of respirations at a dose of 30 mg/kg, i.v. Furthermore, loxiglumide slightly decreased femoral arterial blood flow at doses of more than 3 mg/kg, i.v. On the other hand, it had no effect on contractile force or contraction rate in the isolated guinea pig atrium and resting tension in the isolated rabbit aorta. 4. Gastrointestinal system: Loxiglumide increased bile secretion at doses of 10 and 30 mg/kg, i.v. in anesthetized rats and at doses of 3, 10 and 30 mg/kg, i.v. in anesthetized dogs. However, total bile acid output was not affected by loxiglumide. On the other hand, loxiglumide had no effect on pancreatic secretion, gastric secretion and gastric emptying in rats and intestinal transport activity in mice. 5. Hematology: In vitro, in the case of samples without bovine serum albumin, at concentrations of more than 1.9 x 10(-3) mol/l loxiglumide showed hemolysis, while in the case of samples with bovine serum albumin, at concentrations of more than 6.9 x 10(-3) mol/l loxiglumide showed hemolysis, and its maximal potency was weak compared to albumin-free conditions. On the other hand, in vivo, loxiglumide had no effect on hemolysis. In addition, it had no effect on platelet aggregation, prothrombin time and activated partial thromboplastin time. 6. Miscellaneous pharmacological actions: Loxiglumide had no effect on local anesthetic activity in guinea pigs and renal function in mice. These results suggest that loxiglumide seems to produce no serious side effects on the central nervous system, autonomic nervous system, cardio-respiratory system, gastrointestinal system, hematological and miscellaneous systems at pharmacologically effective doses.
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PMID:General pharmacological profile of the novel cholecystokinin-A antagonist loxiglumide. 945 Jan 67

We studied the nonspecific nature of the histologic findings in the gastric antral vascular ectasia (GAVE) syndrome by using a morphometric comparison with common gastric lesions including hyperplastic polyps and gastritis. Five clinicopathologically confirmed cases of GAVE syndrome and 41 cases of gastric hyperplastic polyps were diagnosed during a 5-year interval at Summa Health Systems (Akron, Ohio). These cases, as well as 16 randomly selected cases of nonspecific gastritis and 9 normal gastric antral biopsy specimens, were evaluated. A semiquantitative comparison of the light microscopic findings believed to be essential in diagnosis of GAVE syndrome, including vascular hyperplasia, mucosal vascular ectasia, intravascular fibrin thrombi, and fibromuscular hyperplasia, was performed. Image analysis morphometric measures of the area ratio (vascular area/total biopsy area), mean vascular area, and number of ectatic vessels per square millimeter of tissue were performed on the CAS 200 Image Analyzer (Becton Dickinson, San Jose, Calif). By morphometric and statistical parametric analysis, several histopathologic variables, including area ratio, mean vascular area, mucosal vascular ectasia, and fibromuscular hyperplasia, did not confidently differentiate the histologic features of gastric hyperplastic polyp from those of GAVE syndrome, but did apparently differentiate GAVE syndrome from gastritis and normal gastric mucosa. The propensity of gastric hyperplastic polyps to undergo prolapse changes and prolapse as one proposed mechanism for development of the GAVE syndrome lesion probably accounts for this morphologic similarity. Specific diagnostic histopathologic changes probably do not exist for the GAVE syndrome.
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PMID:Histopathologic changes are not specific for diagnosis of gastric antral vascular ectasia (GAVE) syndrome: a review of the pathogenesis and a comparative image analysis morphometric study of GAVE syndrome and gastric hyperplastic polyps. 957 73

Four-week oral toxicity studies with cetefloxacin tosylate ((-)-7[3-(R)-amino-2-(S)-methyl-1-azetidinyl]-1-(2,4- difluorophenyl)-1,4-dihydro-6-fluoro-4-oxo-3-quinolinecarboxylic acid tosylate, CAS 141725-88-4 (base), E-4868.Ts) a new quinolone antibacterial agent, were performed in Sprague-Dawley rats and marmoset monkeys at doses of 100, 450, 2000 mg/kg/d and 25, 50, 125, 300 mg/kg/d, respectively. In rats, due to its toxicity the high dose was decreased to 1000 mg/kg/d after 3 days of treatment. Mortality was recorded among high dose rats receiving 2000 or 1000 mg/kg/d. Rats receiving dosages of 450 or 2000/1000 mg/kg/d showed less activated mandibular lymph nodes, cortical lymphocyte depletion of mandibular and/or mesenteric lymph nodes, atrophy of the white pulp of the spleen, cortical atrophy of thymus and thymic apoptosis. Enlarged caeca, increased water consumption and variations in plasma electrolyte levels were observed in animals receiving these dosages and in male rats receiving 100 mg/kg/d. Low neutrophil counts were observed in rats receiving dosages of 100 or 450 mg/kg/d, and increased alkaline phosphatase and alanine transaminase plasma levels and slightly decreased plasma protein levels in females receiving 450 or 2000/1000 mg/kg/d. Marmosets receiving dosages of 50 mg/kg/d and above displayed several clinical signs which included emesis, diarrhoea, ptosis, occasional episodes of under- and overactivity, and excessive scratching activity. Skin reddening was observed during the first week of treatment in marmosets receiving 300 mg/kg/d. On the basis of the results obtained it can be concluded that the non-toxic doses of E-4868. Ts after 4-week oral administration in rats and marmoset monkeys were 100 and 25 mg/kg/d, respectively.
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PMID:Four-week oral toxicity studies of the new quinolone antibacterial agent cetefloxacin tosylate in rats and marmoset monkeys. 1141 45

Acute carotid stent thrombosis (ACST) is a rare complication that can lead to dramatic and catastrophic consequences. A rapid diagnosis and prompt recanalization of the internal carotid artery are needed to minimize the ischemic insult and the reperfusion injury. We reviewed the current literature on this devastating complication of CAS with the intention of investigating the potential causative factors and to define the appropriate management. According to our study discontinuation of antiplatelet therapy, resistance to antiplatelet agents and inherent or acquired thrombotic disorders are the main causes of thrombosis. Technical intraprocedural parameters such as dissection, atheroma prolapse, kinking of the distal part of internal carotid artery and embolic protection device occlusion can also result in early carotid stent thrombosis. Rapid reperfusion ensures an improved neurological outcome and a better prognosis in the short and long term. Thrombolysis, mechanical thrombectomy or thromboaspiration in combination with drug or thrombolytic therapy, surgical therapy and re-angioplasty are treatment options that have been used with encouraging results. In conclusion, optimal perioperative antiplatelet treatment as well as technical considerations regarding the carotid artery stenting plays a determinant role.
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PMID:Acute Carotid Stent Thrombosis: A Comprehensive Review. 2764 27

Introduction: Optical Coherence Tomography (OCT) is an intravascular imaging providing high-resolution images of morphological features of arterial wall. Nowadays, OCT is an accepted intravascular modality to study coronary arteries, stent implantation, and vessel injury. In the last decade, an increasing interest have been focused on the application of OCT in carotid arteries.Areas covered: Literature evidence in the application of OCT in carotid arteries still remains debated. So far, OCT has been used as a research tool, aiming to evaluate atherosclerotic plaques' features and stents' behavior after implantation. This paper is intended to summarize clinical evidences and practices in the use of OCT in carotid arteries district and during CAS procedures. Literature review was completed via Pubmed search using Keywords.Expert opinion: CAS is a safe and effective procedure when performed by trained physicians with a tailored approach. In this scenario, ambiguous pictures at ultrasound, angiography, and IVUS might be clarified using OCT.By providing unprecedented microstructural information on atherosclerotic plaques, OCT may identify the features of vulnerable carotid plaque and, by identifying possible defects after stent implantation as malapposition and plaque prolapse, it may help the tailoring approach to CAS.
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PMID:Clinical considerations and recommendations for OCT-guided carotid artery stenting. 3229 92