Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026837 (muscle rigidity)
 1,077 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of the present study was to investigate physical dependence upon diazepam systematically in two inbred strains of rats, Lewis (LEW) and Fischer 344 (F344). Rats were chronically fed food containing diazepam on an escalating drug dosage schedule, from 1 and 2 to 12 mg/g of food, over a period of 30 days. During treatment, the growth curve in LEW and F344 rats was suppressed compared with the respective controls. Motor incoordination was evaluated by a rotarod performance test. The ranking of the motor incoordination during the final concentration of diazepam was as follows: F344 greater than LEW. After substitution of normal food for the diazepam-admixed food, various signs of diazepam withdrawal occurred 16-120 h later. These signs included vocalization, irritability, muscle rigidity, ear-twitching, Straub's tail, piloerection, fascicular twitch, tremor, convulsion, and death. The incidences of vocalization, ear-twitching, piloerection, and tremor in F344 were significantly higher than those in LEW rats. Furthermore, two of six F344 rats showed spontaneous convulsions and one rat died of convulsions. Overall withdrawal scores were significantly greater in F344 (16.0) than in LEW (6.3) rats. These results suggest that diazepam withdrawal severity is strongly influenced by genetic factors, and F344 rats are highly susceptible to dependence upon benzodiazepines.
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PMID:Genetic differences in the development of physical dependence upon diazepam in Lewis and Fischer 344 inbred rat strains. 143 78

Abecarnil (ZK 112119; isopropyl-6-benzyloxy-4-methoxymethyl-beta-carboxylate) is a metabolically stable beta-carboline derivative with potent anxiolytic and few sedative and ataxic effects in rodents. The anticonvulsant and muscle relaxant actions of abecarnil have been evaluated in mice, rats, gerbils and baboons. Abecarnil raised the threshold for tonic electroconvulsions in mice after corneal but not after auricular application, had no effect on maximal electroshock-induced tonic convulsions triggered by either method, protected mice against the tonic hindlimb extension in PTZ-, picrotoxin- and 3-mercaptopropionate-induced seizures and blocked clonus after PTZ, DMCM (methyl-4-ethyl-6,7-dimethoxy-9H-pyrido-(3,4-b)-indol-3-carboxylate) and 3-mercaptopropionate. Abecarnil had no effect on convulsions induced by bicuculline and strychnine. Furthermore, abecarnil blocked kindled seizures after chronic administration of PTZ and FG 7142 (beta-carboline-3-carboxylic acid methylamide) and protected mice and rats against limbic convulsions induced by pilocarpine. Severity and afterdischarge duration of amygdala-kindled seizures were reduced in rats treated with abecarnil. Abecarnil also antagonized selectively convulsions induced by i.c.v. administration of kainate, but not those triggered by N-methyl-D-aspartate or quisqualate. In genetic models of reflex epilepsy, abecarnil was effective against sound-induced convulsions in DBA/2 mice, against air blast-induced generalized seizures in gerbils and against myoclonus in baboons Papio papio. The anticonvulsant effect of abecornil in a PTZ seizure model in mice was potentiated by ethosuximide, whereas no significant potentiation was found with diazepam, clonazepam, diphenylhydantoin, carbamazepine and phenobarbital. Electromyographic monitoring in a etorphine model of muscle rigidity in rats showed no or little muscle relaxant effect of abecarnil.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anticonvulsant action of the beta-carboline abecarnil: studies in rodents and baboon, Papio papio. 197 Mar 62

Two sibling cases of cerebrotendinous xanthomatosis with parkinsonism were reported. One was a woman of 39 years old, and another was her sister of 36 years old. In both cases, febrile convulsion appeared on 1.5 year old, and mental deterioration, ataxic -spastic gait, cataract and swelling of Achilles tendons developed in order since entrance into elementary school. Five years ago, while they were in hospital at the first time, they were diagnosed as cerebrotendinous xanthomatosis by mental disturbance, cerebellar ataxia, pyramidal tract sign, histologically xanthomatous granuloma of Achilles tendons and hypercholestanolemia and family history of autosomal recessive trait. After the second admission, parkinsonism was noticed in addition to those findings above. Parkinsonism consisted of the following: Resting tremor of parkinsonian type, mild muscle rigidity of forearm and intrinsic-plus hand were observed in the elder sister, and generalized severe rigidity and bradykinesia in the younger sister. In both cases, brain CT showed the pontocerebellar atrophy, and the bilateral low density area in corona radiata, posterior portion of internal capsule, cerebral peduncle, tegmentum of midbrain and deep matter of cerebellum. Brain MRI also showed abnormal intensity in the same regions as on the brain CT. Administration of anti-parkinsonian drugs was challenged for the parkinsonism. Oral L-dopa test (500 mg) moderately improved parkinsonism in both cases. Therapy of diphenylpyraline hydrochloride (10 mg/day) entirely inhibited parkinsonian tremor and mild rigidity in the elder sister but was less effective for severe rigidity in the younger sister than administration of L-dopa.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Parkinsonism associated with cerebrotendinous xanthomatosis]. 226 9

Two cases of severe tetanus admitted to ITU with muscle rigidity and convulsions and needed mechanical ventilation had a continuous infusion of vecuronium as muscle relaxant. The cardiovascular changes of the two patients are described. It is concluded that vecuronium because of its minimal cardiovascular effects is the relaxant of choice in the management of severe tetanus.
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PMID:Vecuronium in the management of tetanus. Is it the muscle relaxant of choice? 289 43

Sex differences in physical dependence on barbital (BAR), which is not readily metabolized in rats, were studied by the drug-admixed food method. The concentration of BAR in the food was gradually increased from 1 and 2 up to 6 and 8 mg/g food concurrently available to each rat over a period of 36 days in both male and female Sprague-Dawley rats. Sedation and muscle relaxation were observed in males at the 4 and 6 mg/g condition and to a greater degree at 6 and 8 mg/g of food. This effect was seen only at the highest drug concentration, 6 and 8 mg/g food, in females. Physical dependence was assessed in both sexes after substitution of normal food for the BAR-admixed food. Various signs of BAR withdrawal were observed including vocalization, irritability, muscle rigidity, tremors and convulsions. The incidence of convulsions was 76.9% in females and 45.5% in males, respectively. Maximum weight loss was 15.4% in females and 12.1% in males. However, brain BAR concentrations in the male rats were higher than that in the female rats 9 hours before onset of withdrawal and at all later time points tested. Thus, we have demonstrated that weak sex differences in physical dependence on BAR exist and suggest that this difference resulted from a difference in CNS sensitivity to BAR.
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PMID:[Sex differences in the physical dependence on barbital in rats]. 382 11

A mixture of 120 mg ketamine hydrochloride (KHCL)/20 mg xylazine hydrochloride (XHCL)/ml was used to immobilize 37 wild mountain lions (Felis concolor) 46 times. Observations were recorded during 37 trials that included kittens, adult females, and adult males. Dosages were based on 11 mg KHCL and 1.8 mg XHCL/kg estimated body weight. Actual doses for 24 lions requiring a single injection for immobilization ranged from 4.7-15.8 mg KHCL/kg and 0.8-2.6 mg XHCL/kg. Induction, duration, and recovery times did not differ (P greater than 0.05) between the sex and age classes. Two kittens were overdosed with the drug combination, but the effects were not life threatening. Eleven other lions, nine of which were initially underdosed, required additional injections of the drug combination for safe handling. Immobilization was characterized initially by semi-consciousness, open eyelids, pupillary dilation, and muscle rigidity. Later, most lions appeared unconscious, muscles relaxed, and breathing slowed considerably. No convulsions or hypersalivation occurred. The KHCL/XHCL mixture given at approximately 11 mg KHCL and 1.8 mg XHCL/kg body weight proved useful for immobilizing wild mountain lions for research purposes. Suggestions for case of immobilized cats are included.
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PMID:Immobilizing wild mountain lions (Felis concolor) with ketamine hydrochloride and xylazine hydrochloride. 395 Oct 66

Sex differences in physical dependence on sodium pentobarbital in the rat were studied by the drug-admixed food (DAF) method. With male rats, the concentration of pentobarbital in the food was gradually increased from 2 to 30 mg/g over a period of 50 days. The final level of drug intake was approximately 1.7 g/kg/day. At pentobarbital concentrations of 20 and 22 mg/g of food, sedation and mild muscle relaxation were observed. At the highest drug concentration, 30 mg/g of food, marked muscle relaxation was noted. With female rats, the concentration of pentobarbital in the food was gradually increased from 1 to 16 mg/g over a period of 47 days. The final level of intake was approximately 1.0 mg/kg/day. At drug concentrations of 12 and 14 mg/g, sedation and mild muscle relaxation appeared. At 16 mg/g, female rats showed marked muscle relaxation similar to that of the male rats. To produce severe loss of muscle tone, the male rats required twice as much pentobarbital as the female rats. After substitution of normal food for the pentobarbital-admixed food, various signs of pentobarbital withdrawal occurred in both sexes. These signs included vocalization, irritability, muscle rigidity, tremors and convulsions. Onset of withdrawal was more rapid in the females, and the maximum weight loss was greater, 8.0% compared to 3.8% in the males. Physical dependence on pentobarbital was easily developed in both sexes by the DAF method. There was a marked sex difference in withdrawal which we attribute to sex differences in drug metabolizing enzyme activity.
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PMID:Sex differences in the induction of physical dependence on pentobarbital in the rat. 409 88

The results of a broad pharmacological screening on 1-[(2,4-dichlorophenyl)-methyl] -1H-indazole-3-carboxylic acid ( lonidamine ) a new antitumour agent which also possesses antispermatogenic and embryotoxic effects, are reported. Lonidamine does not affect general behaviour and autonomic functions and is devoid of anticonvulsant, anti-reserpine, anti-apomorphine, anti-amphetamine, antitremor , antipyretic, antiinflammatory and analgesic effects. It also lacks those side effects which are considered characteristic of different antitumour agents, such as thymus and spleen atrophy, delay in skin wound healing and damage to the gastrointestinal mucosa. At doses 40 times higher than that of hydrochlorothiazide, lonidamine produces diuretic effects. The practical importance of these findings in the current therapeutic use of lonidamine appears to be limited. The most typical signs of acute intoxication produced by high doses of lonidamine are salivation, lacrimation, diarrhea, ataxia, muscle rigidity and prostration with superimposed convulsions.
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PMID:Pharmacological investigations on lonidamine. 654 Jan 4

We studied the involvement of beta-adrenoceptors in the physical dependence formation of barbital. 1. Propranolol (at a dose of 0.5 or 1.0 mg/g food) and barbital were applied simultaneously as a mixture with animal food (barbital-propranolol combination). Barbital was applied on a schedule of gradually increasing dosages from 0.5-and-1.0 to 6-and-8 mg/g food over 36 days. Only the animals dosed with barbital exhibited severe withdrawal signs such as spontaneous withdrawal convulsions. The animals dosed with propranolol alone showed no changes even on withdrawal of the drug. The formation of physical dependence on barbital was obviously inhibited by the combination of barbital and propranolol. 2. Cross-application of propranolol (30 and 60 mg/kg, p.o., and 10 and 30 mg/kg, i.p.) following withdrawal of barbital resulted in the inhibition of the spontaneous withdrawal convulsions, muscle rigidity and hyperirritability. It also inhibited significantly tranylcypromine-induced convulsions, while it failed to inhibit similarly induced hyperthermia. These results including previous findings of effects of monoamine-related compounds on barbital withdrawal convulsions suggest that the balance of activities of noradrenergic neurons, especially that of alpha- and beta- receptors, has great influence on both the formation of physical dependence on barbital and the manifestation of withdrawal convulsions.
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PMID:Effects of propranolol on barbital dependence formation and withdrawal signs. 668 67

Antidepressant drugs are among the most commonly encountered causes of self-poisoning. These drugs include tricyclics, tetracyclics, bicyclics and monocyclics, as well as monoamine oxidase (MAO) inhibitors and selective serotonin reuptake inhibitors (SSRIs). Of these, the tricyclic antidepressants (TCAs) are generally more toxic in overdose, with major toxicity usually manifesting within the first 6 hours after overdose. Various studies indicate that patients at risk of toxicity from TCA overdose may be identified by neurological, cardiovascular and electrocardiography status, together with a quantitative estimate of the plasma drug concentration. While there are various methods available for such chemical estimations, the most satisfactory appears to be fluorescence polarisation immunoassay which gives rapid quantitative results for a variety of TCAs. The selective MAO-A inhibitor antidepressants and the SSRIs are relatively nontoxic when taken alone. However, overdoses of combinations of MAO inhibitors and either SSRIs or TCAs with serotonin reuptake blocking activity may result in a serotonin syndrome with a severe or fatal outcome. Features of this syndrome include hyperpyrexia, disseminated intravascular coagulation, convulsions, coma and muscle rigidity, which may not develop until 6 to 12 hours after overdose. While quantitative chemical identification of these drugs following overdose is helpful in confirming the diagnosis, it is not mandatory. The increasing use of MAO-A inhibitors and SSRIs in the treatment of depression suggests that careful clinical observation is required when combination overdoses are suspected.
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PMID:Antidepressant toxicity and the need for identification and concentration monitoring in overdose. 852 78


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