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

Dogs, surgically implanted with a chronic gastric fistula, were chronically dosed with N-desmethyldiazepam (32 mg/kg/day) in four divided doses to attain N-desmethyldiazepam plasma levels comparable to those observed in dogs dependent on diazepam (60 mg/kg/day). The time course of N-desmethyldiazepam abstinence was studied, beginning not less than 2 weeks after stabilization levels had been achieved. The abstinence syndrome observed after abrupt discontinuation of N-desmethyldiazepam was similar to the diazepam abstinence syndrome but differed in several important aspects. In diazepam-dependent dogs, there was a short burst of tremor very early in withdrawal (approximately 1-2 hr after the last dose of diazepam) that was not seen in N-desmethyldiazepam-dependent dogs. Signs of abstinence such as tremor, hot foot walking and twitches and jerks were more frequently observed in N-desmethyldiazepam-dependent dogs than in diazepam-dependent dogs as were decreases in food and water intake and in body weight. The overall intensity of abstinence, as measured by the Diazepam Withdrawal Abstinence Scale, was greater in N-desmethyldiazepam-dependent dogs than in dogs dependent on either lorazepam or diazepam. Plasma levels of N-desmethyldiazepam and oxazepam were nearly equal in dogs dependent on diazepam or on N-desmethyldiazepam and were 4 to 10 times greater than the plasma levels of diazepam or lorazepam in diazepam- or lorazepam-dependent dogs, respectively. Furthermore, the plasma levels of N-desmethyldiazepam and oxazepam declined much more slowly than the levels of diazepam and lorazepam. These results suggest that physical dependence on diazepam is caused by the accumulation and actions of N-desmethyldiazepam.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:N-desmethyldiazepam physical dependence in dogs. 393 42

The effects of diazepam, dantrolene and atropine on drug-induced tremors were investigated in mice from the point of view of the tremor frequency. The study involved a power spectral analysis of the random current induced by movement of a magnet (attached to the mouse) on a wire coil. To induce tremor, tremorine and harmaline were subcutaneously injected. The power spectral density function defined the frequency composition of the tremor and its severity was determined quantitatively in terms of the mean square value of the data in any frequency range of concern. Diazepam markedly depressed the power spectral density of the tremorine- and harmaline-induced tremor and reduced the tremor frequency. With higher doses of diazepam, the peak frequency of the tremorine-induced tremor shifted to the lower frequency side as if the tremor components were taken into the component of the spontaneous motor activity. Dantrolene and atropine suppressed the power spectral density without affecting tremor frequency. The relationship between the change of tremor frequency and the site of action of antitremorgenic agents are discussed.
 ...
PMID:Further studies on quantification of drug-induced tremor in mice: effects of antitremorgenic agents on tremor frequency. 398 59

Dogs, surgically implanted with a gastric fistula, were chronically dosed with diazepam or lorazepam. Diazepam (60 mg/kg/day) or lorazepam (100 mg/kg/day) was administered intragastrically in four divided daily doses. Beginning no less than 2 weeks after the attainment of stabilization doses, dogs underwent withdrawal experiments, repeated at 2-week intervals. At a time of withdrawal determined by a Latin square crossover design, dogs were observed for 8 hr for signs of abstinence. Both diazepam and lorazepam caused a withdrawal abstinence syndrome to appear upon abrupt discontinuation of the drug. The two abstinence syndromes had many signs in common, including tremor, hot foot walking, rigidity and decreased food intake, but the lorazepam withdrawal abstinence syndrome was much less intense and had a shorter latency to onset than the diazepam abstinence syndrome, which also included clonic and tonic-clonic convulsions and was lethal in two dogs. Furthermore, the diazepam withdrawal abstinence syndrome was biphasic, the first phase apparent by 24 hr and a second phase beginning at 48 hr, whereas the lorazepam syndrome was not. Diazepam suppressed the major signs of diazepam abstinence in a dose-related manner, but failed to completely suppress all signs of abstinence. CGS-8216, a pyrazoloquinoline benzodiazepine antagonist, precipitated abstinence in the diazepam-dependent dog, but did not precipitate tonic-clonic seizures. No abstinence syndrome was precipitated in the lorazepam-dependent dog. These results would suggest that whereas diazepam and lorazepam both cause physical dependence the two syndromes are not the same and, furthermore, that physical dependence on, and withdrawal from, diazepam involves at least two separate mechanisms with different selectivity for benzodiazepine agonists and antagonists.
 ...
PMID:Physical dependence on diazepam and lorazepam in the dog. 613 1

The effects of 40 mg nadolol versus 2 mg diazepam on performance anxiety of 33 young music students were determined. The study had a double-blind, crossover design and was placebo controlled. Nadolol attenuated the rise in pulse rate caused by anxiety and improved those aspects of string playing that can be adversely affected by tremor. There was also a tendency for other functions requiring coordination and judgment to improve. No effect on anxiety was noted for nadolol or for 2 mg diazepam. Diazepam, however, did cause some minor deterioration of performance that was not related to anxiety change. These findings, taken with others, suggest that beta-adrenoceptor-blocking drugs such as nadolol have an important role in the correction of anxiety-induced disturbances of performance. Indeed, their use under such circumstances probably is preferable to that of the benzodiazepines.
 ...
PMID:Beneficial effect of nadolol on anxiety-induced disturbances of performance in musicians: a comparison with diazepam and placebo. 614 77

The seizure threshold for different seizure components was measured after slow intravenous infusion of bicuculline in the rat. Clear differences were seen in the seizure threshold for tremor (TRE) and clonic-forepaw (CLOF) as compared to clonic-hindpaw (CLOH) and tonic-forepaw (TONF). Seizure threshold was measured after treatment with different doses of diazepam, pentobarbital, D-etomidate, picrotoxin, RO15-1788 and (+/-)-5-(1,3,-dimethylbutyl)-5-barbituric acid (DMBB). Direct and indirect antagonism between the agonists and antagonists was examined. The interactions between the drugs for TRE and CLOF resemble those described in in vitro receptor-binding assays using the GABA-benzodiazepine-chloride ionophore complex (GBCI). The interactions for CLOH and TONF do not show this resemblance, suggesting less involvement of GABA in these phenomena. Diazepam was selectively antagonized by RO15-1788. D-Etomidate and pentobarbital were directly antagonized by DMBB, suggesting shared activity at the barbiturate site. No evidence was found for an interaction between compounds acting at different sites within the GBCI.
 ...
PMID:Diazepam, pentobarbital and D-etomidate produced increases in bicuculline seizure threshold; selective antagonism by RO15-1788, picrotoxin and (+/-)-DMBB. 631 5

The spectra of pharmacological effects of ethanol and the benzodiazepine show a degree of overlap. Neurophysiological and neurochemical evidence indicates that both ethanol and benzodiazepines facilitate inhibitory neurotransmission mediated by GABA. Diazepam has been reported to inhibit both the tremor and mechanism of cerebellar cyclic GMP caused by harmaline by a neurotransmission in the cerebellum. Because of the similarities between ethanol and benzodiazepines, the effects of ethanol on harmaline-induced tremor and increase of cerebellar cyclic GMP were studied. Ethanol inhibited harmaline-induced tremor at doses as low as 0.1 g/kg. At this low dose, however, a dissociation between inhibition of harmaline tremor and inhibition of the harmaline-induced increase of cerebellar cyclic GMP was observed.
 ...
PMID:Ethanol effects on harmaline-induced tremor and increase of cerebellar cyclic GMP. 631 33

Tofizopam, an anxiolytic 3,4-benzodiazepine, increases the affinity of benzodiazepine receptors for 1,4-benzodiazepines. In this study we investigated whether this increased affinity of the receptors alters the sensitivity of mice to tremor and to convulsions. Convulsions induced by harmane were not affected by tofizopam (50-300 mg/kg), but diazepam (15 mg/kg) increased the ED50 of harmane from 9.9 to 25.1 mg/kg. Tofizopam did not alter the threshold for electroshock-induced convulsions, while a dose of 10 mg/kg diazepam protected mice from convulsions. Low doses of tofizopam (12.5-25 mg/kg) sensitized mice to the tremorogenic effect of harmaline. Diazepam inhibited tremor: the ED50 of harmaline increased by 153% after 50 mg/kg of diazepam. In contrast to 1,4-benzodiazepines, tofizopam has no anticonvulsive effect. It sensitises mice to the tremor induced by harmaline. In combination with diazepam, however, tofizopam enhanced the anticonvulsive and antitremorogenic actions of this 1,4-benzodiazepine by 12-65%. This effect probably results from a tofizopam-induced increase in the occupation of benzodiazepine receptors.
 ...
PMID:Tofizopam enhances the action of diazepam against tremor and convulsions. 684 90

The sorption of diazepam in large-volume i.v. admixtures to administration-set components and in i.v. containers was analyzed quantitatively. Solubility of diazepam in phosphate buffer at various pH levels and in i.v. fluids was measured. Partition coefficients of diazepam into components of i.v. administration sets and i.v. containers were studied by shaking a solution of diazepam in 0.9% sodium chloride, with finely cut components and measuring the change in diazepam in the aqueous phase. Flow studies through an administration set of a 0.04-mg/ml diazepam solution in 5% dextrose injection were done, varying both the flow rate and the length of tubing. The maximum free-base solubility of diazepam in phosphate buffer was 0.048 mg/ml; its solubility was 0.058, 0.050, and 0.064 mg/ml in lactated Ringer's, 0.9% sodium chloride, and 5% dextrose injections, respectively. Equilibrium partition coefficients were highest for polyvinyl chloride tubing and flexible bags. Volume-control sets made of cellulose propionate had lower but sufficiently large partition coefficients to cause diazepam loss. Polyolefin semi-rigid and glass containers had low partition coefficients. In the flow studies, the amount of solution-contact time correlated with the extent of absorption. As flow rate decreased or tubing length increased, the amount of diazepam absorbed increased proportionately. A nomogram and a predictive dosing chart are presented for calculation of actual diazepam doses delivered at various flow rates and tubing lengths. Diazepam can be administered safely and effectively by i.v. infusion. The use of volume-control sets and flexible polyvinyl chloride bags should be avoided with diazepam solutions. Polyolefin semi-rigid containers are acceptable alternatives to glass. The concentration of diazepam infusions should not exceed 0.04 mg/ml.
 ...
PMID:Factors affecting diazepam infusion: solubility, administration-set composition, and flow rate. 729 34

Recent research suggests that the GABAB receptor may mediate some of the acute effects of alcohol, but little is known of its involvement in alcohol withdrawal. Mice made dependent on alcohol exhibited tremor and tail arch when consumption ceased. Diazepam dose-dependently attenuated both tremor and tail arch, whereas baclofen had no effect on either of these two withdrawal symptoms. However, baclofen dose-dependently induced convulsant behaviour in the withdrawing mice, and this was significantly attenuated by the GABAB antagonists phaclofen (50 mg/kg) and CGP 35348 (300 mg/kg), but not BPBA (50 mg/kg). Phaclofen, BPBA, and CGP 35348, when administered alone and in combination with a single dose of baclofen, did have an effect on tremor, although the magnitude was small in comparison to that seen with diazepam. It appears that the GABAB receptor may play a role in mediating convulsions during alcohol withdrawal, and that in this system baclofen is proconvulsant.
 ...
PMID:The effects of GABAB ligands on alcohol withdrawal in mice. 786 8

In this study, the effects of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, on ethanol withdrawal symptoms, were compared with those of diazepam and propranolol. The rats were given highly intoxicating doses of ethanol for 4 days. After the intoxication period, rats were divided into four equal groups: a dexmedetomidine-treated group (30 micrograms/kg, sc), a diazepam-treated group (2 mg/kg, sc), a propranolol-treated group (5 mg/kg, sc), and a control group with no medication. Medication was given in the withdrawal phase-2, 8, 14, and 20 hr after the onset of the withdrawal symptoms. The severity of the ethanol withdrawal symptoms (rigidity, tremor, irritability, and hypoactivity) was observed up to 33 hr after the onset of the ethanol withdrawal symptoms. Both dexmedetomidine and diazepam significantly relieved tremor compared with the control group. Diazepam reduced irritability significantly, compared with the control group. When measured as the sum score of the three most specific withdrawal signs (rigidity, tremor, and irritability), dexmedetomidine and diazepam significantly relieved the ethanol withdrawal reaction. Propranolol attenuated tremor, but was inefficient against other withdrawal symptoms. Dexmedetomidine may thus represent a new effective drug in the treatment of the ethanol withdrawal syndrome.
 ...
PMID:Dexmedetomidine, diazepam, and propranolol in the treatment of ethanol withdrawal symptoms in the rat. 926 29


<< Previous 1 2 3 Next >>