Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclopiazonic acid (CPA) was found to have many pharmacological properties in common with the antipsychotic drugs chlorpromazine and reserpine. Thus, in mice CPA at ip doses of 5-14 mg/kg body weight produced hypokinesia, hypothermia, catalepsy, ptosis, sedation without loss of righting reflex, tremor, gait disturbance, dyspnoea, opisthotonus, atypical convulsion and prolonged barbiturate-induced sleep. The ip LD50 of CPA was found to be 13 +/- 0.05 mg/kg. The tremors induced by near-lethal doses of CPA were associated with voluntary or forced movements (action tremors); they worsened during the days following treatment, but they were weak compared with the exhausting and continuous tremors of the whole body caused by 20 mg tremorine/kg (used for comparison). When death occurred only 24-259 min after administration of CPA (11-14 mg/kg), it was preceded by dypsnoea, cyanosis, opisthotonus and clonic leg movements and tonic extension of hind legs (convulsions). When death was delayed (2-6 days after CPA administration), it was preceded by prostration, ptosis, hypothermia, tremor and cessation of food and water intake resulting in cachexia; convulsions were not seen in this group of mice. CPA did not affect the rate of convulsion or death caused by either maximal electroshock or metrazol administration but it did delay the onset of metrazol-induced seizures. In rabbits, 10 mg CPA/kg body weight initially produced tachycardia, tachypnoea and sedation with an activated electroencephalogram. Of three rabbits given 10 mg CPA/kg one died, and in this rabbit slow delta waves were seen just before and during a brief period with clonic leg movements. In this animal death was accompanied by tonic extension of the hind legs, respiratory arrest and cardiac fibrillation; and epileptiform EEG was not seen at any time. The unexpected EEG activation with sedation in rabbits treated with CPA was similar to the effect of reserpine on EEG.
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PMID:Toxicity and neuropharmacology of cyclopiazonic acid. 404 83

Previous studies have shown indirectly that the neuromuscular effects of nonselective cholinesterase inhibitors are mediated through the inhibition of acetylcholinesterase (AChE). To test this hypothesis more directly we studied the effects of the specific inhibitor of AChE, BW 284c51, at the neuromuscular junction of rat diaphragms. BW 284c51 inhibits AChE in a dose-dependent partially reversible manner at all concentrations tested (10(-9) to 10(-4) M). Maximum inhibition was never greater than 92%. The drug increased miniature end-plate potential (MEPP) amplitude and prolonged half-decay time at 10(-7) and 10(-6) M. However, BE 284c51 had no effect on the resting membrane potential at any concentration. BW 284c51 at 10(-7) M reversibly increased MEPP frequency by almost 4-fold. There was a 2-fold increase in the occurrence of giant MEPPs in the presence of BW 284c51. The quantum content (m) of the end-plate potential was increased in 10(-7) M BW 284c51 as were end-plate potential amplitude and quantum size (q). Animals injected subcutaneously with 10 mg/kg of BW 284c51 displayed typical signs of AChE inhibition including salivation, whole body tremor and prostration. Spontaneous muscle fasciculation was more noticeable after in vivo injection of BW 284c51 than after in vitro administration. Furthermore, MEPP frequencies were considerably faster when the drug was injected in vivo than when applied in vitro. The data are discussed with respect to the hypothesis that inhibition of AChE causes presynaptic as well as postsynaptic effects.
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PMID:Presynaptic and postsynaptic neuromuscular effects of a specific inhibitor of acetylcholinesterase. 625 19

1 N,N-Dimethyltryptamine (DMT) in pargyline pretreated rodents induced a dose-dependent behavioural syndrome consisting of hyperactivity, prostration and hindlimb abduction, mild tremor, Straub tail, retropulsion and jerking. 2 In rats pretreated with pargyline, the behavioural syndrome induced by DMT differed from that induced by L-tryptophan or quipazine, in the lack of forepaw treading and head-weaving and in the presence of only mild tremor. 3 The hyperactivity component of the DMT-induced behavioural syndrome in pargyline-pretreated mice was potentiated by cyproheptadine, methergoline, and mianserin, inhibited by cinanserin, haloperidol, pimozide, methiothepin and propranolol, and not affected by 501C67-sulphate and methysergide. 4 The maximal behavioural changes induced by DMT in rats, other than hyperactivity, were unaffected by pretreatment with cyproheptadine, methysergide, and cinanserin. However, propranolol reduced the intensity of all behavioural effects apart from body jerking, and methergoline decreased the duration of prostration. Phenoxybenzamine and haloperidol, in contrast, enhanced prostration. 5 DMT plus pargyline did not induce circling behaviour in mice with a unilateral 6-hydroxy-dopamine lesion of the nigro-striatal pathway. 6 The DMT-induced behavioural syndrome appears to consist of two components, (a) hyperactivity and (b) other behavioural changes. They differ in their response to drugs affecting brain monoamines. The hyperactivity component may be expressed via dopamine mechanisms, but the other behavioural changes are not. The two behaviours do not respond consistently to drugs believed to alter brain 5-hydroxytryptamine function.
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PMID:Behavioural changes induced by N,N-dimethyl-tryptamine in rodents. 676 27

The intravenous toxicity to the rat of 36 pyrethroids has been examined. With two exceptions they cause either (1) T-syndrome, consisting of aggressive sparring, sensitivity to external stimuli, fine progressing to gross whole body tremor and prostration or (2) CS-syndrome, consisting of pawing and burrowing behaviour, salivation, coarse tremor, progressing to sinuous writhing (choreoathetosis) and clonic seizures. The two exceptions presented a TS-syndrome with salivation associated with the T-syndrome. No clearcut relationship between chemical structure and symptoms of poisoning has emerged through some generalisations are discussed.
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PMID:Structure-activity relationships of some pyrethroids in rats. 744 3

The technical grade of xylenes (mixed) (hereafter termed xylenes) contains the three isomeric forms and ethylbenzene (percentage composition shown above). The annual production for 1985 was approximately 7.4 x 108 gallons. Xylenes is used as a solvent and a cleaning agent and as a degreaser and is a constituent of aviation and automobile fuels. Xylenes is also used in the production of benzoic acid, phthalate anhydride, and isophthalic and terephthalic acids as well as their dimethyl esters. Toxicology and carcinogenesis studies of xylenes were conducted in laboratory animals because a large number of workers are exposed and because the long- term effects of exposure to xylenes were not known. Exposure for the present studies was by gavage in corn oil. In single-administration studies, groups of five F344/N rats and B6C3F1 mice of each sex received 500, 1,000, 2,000, 4,000, or 6,000 mg/kg. Administration of xylenes caused deaths at 6,000 mg/kg in rats and mice of each sex and at 4,000 mg/kg in male rats. In rats, clinical signs observed within 24 hours of dosing at 4,000 mg/kg included prostration, muscular incoordination, and loss of hind limb movement; these effects continued through the second week of observation. Tremors, prone position, and slowed breathing were recorded for mice on day 3, but all mice appeared normal by the end of the 2- week observation period. In 14- day studies, groups of five rats of each sex were administered 0, 125, 250, 500, 1,000, or 2,000 mg/kg, and groups of five mice of each sex received 0, 250, 500, 1,000, 2,000, or 4,000 mg/kg. Chemical- related mortality occurred only at 2,000 mg/kg in rats and at 4,000 mg/kg in mice. Rats and mice exhibited shallow breathing and prostration within 48 hours following dosing at 2,000 mg/kg. These signs persisted until day 12 for rats, but no clinical signs were noted during the second week for mice. In 13- week studies, groups of 10 rats of each sex received 0, 62.5, 125, 250, 500, or 1,000 mg/kg, and groups of 10 mice of each sex received 0, 125, 250, 500, 1,000, or 2,000 mg/kg. No deaths or clinical signs of toxicity were recorded in rats. However, high dose male rats gained 15% less weight and females 8% less weight than did the vehicle controls. Two female mice died at the 2,000 mg/kg dose. Lethargy, short and shallow breathing, unsteadiness, tremors, and paresis were observed for both sexes in the 2,000 mg/kg group within 5- 10 minutes after dosing and lasted for 15- 60 minutes. Two- year toxicology and carcinogenesis studies were conducted by administering 0, 250, or 500 mg/kg xylenes in corn oil by gavage to groups of 50 F344/N rats of each sex, 5 days per week for 103 weeks. Groups of 50 B6C3F1 mice of each sex were administered 0, 500, or 1,000 mg/kg xylenes on the same schedule. Although the mortality was dose related in male rats (final survival: vehicle control, 36/50; low dose, 26/50; high dose, 20/50), many of the early deaths in the dosed males were gavage related. Body weights of the high dose male rats were 5%- 8% lower than those of the vehicle controls after week 59. The mean body weights of low dose and vehicle control male rats and those of dosed and vehicle control female rats were comparable. Survival rates of female rats and both sexes of dosed mice were not significantly different from those of the vehicle controls. The mean weights of dosed male and female mice were comparable to those of the vehicle controls. Hyperactivity lasting 5- 30 minutes was observed in high dose mice after dosing, beginning after week 4 and continuing through week 103. At no site was the incidence of nonneoplastic or neoplastic lesions in dosed rats or mice of either sex considered to be related to the administration of xylenes. Neither xylenes nor any of its components (o- xylene, m-xylene, p- xylene, or ethylbenzene) were mutagenic when tested with or without metabolic activation in Salmonella typhimurium strains TA100, TA1535, TA97, or TA98 with the preincubation protocol. In addition, ethylbenzene was tested in cytogenetic assays using cultured Cetic assays using cultured Chinese hamster ovary cells both with and without metabolic activation; neither sister- chromatid exchanges nor chromosomal aberrations were induced by ethylbenzene. An audit of the experimental data was conducted for the 2-year studies of xylenes. No data discrepancies were found that influenced the final interpretations. Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenicity of xylenes (mixed) for male or female F344/N rats given 250 or 500 mg/kg or for male or female B6C3F1 mice given 500 or 1,000 mg/kg.
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PMID:NTP Toxicology and Carcinogenesis Studies of Xylenes (Mixed) (60% m-Xylene, 14% p-Xylene, 9% o-Xylene, and 17% Ethylbenzene) (CAS No. 1330-20-7) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 1273 97

Butanal oxime is used as a volatile antiskinning agent in paints, inks, and similar products. Butanal oxime was chosen for toxicology testing as a representative of the aldoxime class. Male and female F344/N rats and B6C3F1 mice received butanal oxime (99 percent pure) in drinking water for 15 days or by gavage in 0.5 percent methylcellulose for 14 weeks. Animals were evaluated for clinical pathology, reproductive system effects, and histopathology. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse peripheral blood erythrocytes. In the 15-day studies, groups of five male and five female rats and mice received 0, 312, 625, 1,250, 2,500, or 5,000 ppm butanal oxime in drinking water, resulting in average daily doses of approximately 40, 70, or 100 mg butanal oxime/kg body weight to male and female rats; 45, 90, 130, 200, or 300 mg/kg to male mice; and 45, 85, 100, 130, or 170 mg/kg to female mice. Due to body weight loss and lack of water consumption, all male and female rats receiving 2,500 or 5,000 ppm were removed from the study on day 9; average daily doses were not calculated for these groups. All other rats and mice survived until the end of the studies. Mean body weights of 1,250 ppm male and female rats and 2,500 and 5,000 ppm male and female mice were significantly less than those of the controls. Male mice receiving 5,000 ppm and females receiving 2,500 or 5,000 ppm lost weight during the study. Water consumption by rats and mice receiving 1,250 ppm or greater was less than that by the controls. Thinness in 2,500 and 5,000 ppm rats and mice was the only clinical finding of toxicity. Spleen weights were significantly decreased in 2,500 and 5,000 ppm female mice. No chemical-related lesions were observed grossly; histologic examinations were not performed. In the 14-week studies, groups of 10 male and 10 female rats and mice received butanal oxime by gavage at doses of 0, 25, 50, 100, 200, or 600 mg/kg, 5 days per week for 14 weeks. All 600 mg/kg rats died or were killed moribund during the first week of the study; in the 600 mg/kg mouse groups, seven males and nine females died, were killed moribund, or were killed accidentally before the end of the study. Mean body weights of 100 and 200 mg/kg male rats, 600 mg/kg male mice, and female mice administered 50 mg/kg or greater were less than those of the controls. Clinical findings of toxicity in 600 mg/kg rats included loss of coordination, wobbly gait, shaking, blinking, constant grooming and scratching of the face, head weaving, burying of the face in bedding, lethargy, and prostration; in 600 mg/kg mice, clinical findings included ataxia, loss of balance after rearing, squinting, and burying of the face in the bedding. Hematology results of the 14-week gavage studies indicate that butanal oxime induces a methemoglobinemia and a responsive anemia in rats and mice. Spleen weights of 100 and 200 mg/kg male rats, female rats administered 50 mg/kg or greater, and 200 and 600 mg/kg male mice were increased, as were the liver weights of 200 mg/kg female rats and mice. In animals that died early due to butanal oxime administration, hepatocellular necrosis was the primary pathologic finding. Degeneration of the nasal olfactory epithelium was observed in dosed rats and mice that died early as well as in animals that survived to the end of the studies. Additional chemical-related nasal findings were respiratory epithelial changes in male rats and suppurative exudate in male and female mice. Increased incidences and/or severities of splenic hematopoietic cell proliferation and pigmentation (hemosiderin) as well as bone marrow hyperplasia were also observed in dosed groups, particularly in the 200 and 600 mg/kg groups, and were indicative of erythrocyte damage. Butanal oxime (3 to 10,000 ug/plate) was mutagenic in S. typhimurium strain TA1535 in the presence of 5 percent or 10 percent rat liver S9; an equivocal response was seen in TA100 with 30 percent rat S9, and no mutagenic activity was seen in TA98, with or without rat or hamster liver S9. Butanal oxime induced chromosomal aberrations in cultured Chinese hamster ovary cells, with and without S9. Significant increases in the frequencies of micronucleated normochromatic erythrocytes were observed in vivo in peripheral blood of male and female mice administered 25 to 600 mg/kg butanal oxime for 14 weeks by gavage. Synonyms: Butanaloxime; butylaldoxime; butyraldehyde oxime; n-butyraldehyde oxime; butyraldoxime; n-butyraldoxime Trade names: Exkin 1, Exkin No. 1 Anti-Skinning Agent, Skino #1, Troykyd Anti-Skin BTO
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PMID:NTP technical report on the toxicity studies of Butanal oxime (CAS No. 110-69-0) administered in drinking water and by gavage to F344/N rats and B6C3F1 mice. 1501 36