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)

N-carbamoyl-2-(2,6-dichlorophenyl) acetamidine hydrochloride (LON 954) causes a reproducible rest tremor in mice, of rapid onset and short duration with no associated rigidity or akinesia and in the absence of any marked changes in body temperature or accompanying peripheral parasympathomimetic effects. This tremor can be antagonised by the dopamine receptor agonists L-Dopa, bromocriptine, nomifensine and piribedil, as well as by anticholinergic anti-Parkinson drugs having an inhibitory effect on dopamine uptake such as benapryzine and benztropine. In contrast, benzhexol, orphenadrine and amantadine had no effect. LON 954 appears to be more specific than oxotremorine for the detection of drugs having therapeutic potential in the treatment of Parkinson's disease, particularly those exerting their effect through dopaminergic systems. An antagonist (BS 100-141), which is a structural isomer of LON 954, is also described.
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PMID:The production of an alternative laboratory model of the Parkinson syndrome using a new benzylimidoylurea derivative LON 954. 40

The tremorogenic properties of a series of benzylimidoylurea derivatives are described. The most potent member, N-carbamoyl-2-(2,6-dichlorophenyl) acetamidine hydrochloride (LON-954), produces a reproducible, dose-dependent rest tremor in the mouse with oral doses of 5-100 mg/kg which is also seen in other species (rat, cat, dog, rabbit). The tremor is of constant frequency, rapid onset and short duration. It is not accompanied by akinesia, muscle ridigity, antinociceptive activity, parasympathomimetic effects or marked hypothermia and in these respects differs from tremor produced by oxotremorine. Pretreatment with a microsomal enzyme inhibitor had no effect on the tremor. An LD50 of 165 mg/kg p.o. was calculated in the mouse. After repeated administration both acute and chronic tolerance developed to the tremorogenic effects of LON-954. Evidence for a central site of action is presented, since the tremor could be reproduced following injection of small quantities (50-100 microgram) into the cerebral ventricles of the mouse. Furthermore, the use of spinal, decorticate and and decerebrate rats indicated that although tremor is not of cortical origin, it arises in an area rostral to the inferior colliculi. The mechanism underlying the tremor appears to involve dopaminergic pathways, since the action of LON-954 was antagonised by L-dopa and apomorphine and potentiated by pimozide. Atropine and carbachol were without effect. It is suggested that LON-954 could be used as an alternative to oxotremorine for the detection of anti-Parkinson drugs, particularly those exerting their effects through dopaminergic mechanisms.
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PMID:The pharmacology of N-carbamoyl-2-(2,6-dichlorophenyl)acetamidine hydrochloride (LON-954) a new tremorogenic agent. 58 44

LON-954 [N-carbamoyl-2-(2,6-dichlorophenyl) acetamidine hydrochloride], a novel tremorogen known to affect the central dopaminergic system, has been investigated in rats for tremor and 5-hydroxytryptamine (5-HT) metabolism. Five, 10 and 20 mg/kg of LON-954 IP caused a reproducible and consistent tremor with a high frequency (16 Hz) within 2 minutes and lasting 30-45 minutes. 5-HT content of the tuberculum olfactorium and basal ganglia was found to be increased significantly at a time when 5-hydroxyindoleacetic acid (5-HIAA) content showed a decrease. 5-HT and 5-HIAA of medulla oblongata showed significant changes only after 15 minutes. The alterations in the levels of the indoleamine in tuberculum olfactorium and its relationship with dosage as well as duration and intensity of LON-954 tremor indicate the involvement of the mesolimbic system in its action. A direct role of 5-HT in LON-tremor was evidenced since the drug failed to produce tremor in rats pretreated with p-chlorophenylalanine (300 mg/kg IP) for 3 days.
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PMID:Tremorogenesis by LON-954 [N-carbamoyl-2-(2,6-dichlorophenyl) acetamidine hydrochloride]: evidence for the involvement of 5-hydroxytryptamine. 270 33

The tremors induced by harmine, LON-954 (N-carbamoyl-2-(2,6-dichlorophenyl)acetamidine hydrochloride) and 5-hydroxytryptophan (5-HTP) were studied in control rats and in rats withdrawn for 16-48 hrs from 6 to 9 days' ethanol administration. The frequencies and the intensities of the tremors were determined electronically. In control rats the frequency spectra of the tremors induced by harmine (20 mg/kg) and LON-954 (10 mg/kg) showed a narrow peak frequency at about 10 Hz. Atropine (1.2 mg/kg) altered neither the frequency nor the intensity of these tremors. 5-HTP (50 mg/kg) when given 3.5 hrs after iproniazid (100 mg/kg) induced tremor with peak frequencies at 6-7 Hz and 12 Hz. In ethanol-withdrawn rats treated with harmine or LON-954 the frequency analysis of tremor revealed a narrow peak frequency at about 12 Hz, which was neither the characteristic frequency of ethanol withdrawal tremor (6 Hz) nor that of harmine or LON-954 (10 Hz). The intensity of both harmine- and LON-954-induced tremor was significantly increased in ethanol-withdrawn rats. The ethanol-withdrawn rats were markedly sensitized to the effect of iproniazid+ 5-HTP, shown by deaths. The peak frequencies of this tremor were the same as those in control rats. The results suggest that harmine-induced tremor involves a dopaminergic-5-HT'ergic imbalance and the tremor induced by LON-954 a dopaminergic-cholinergic imbalance in the brain. The tremor in ethanol-withdrawn rats seems to be mediated by alterations in the activity of the cerebral 5-HT'ergic system.
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PMID:Harmine-, LON-954- and 5-hydroxytryptophan-induced tremors in rats withdrawn from ethanol. 387 87

Tremor produced in laboratory mice by the benzylimidoylurea derivative LON 954 was potentiated in a dose-dependent manner by a variety of typical and atypical neuroleptics. The most effective agents in this respect were those shown by other workers to have a selective action at dopamine receptors, notably the butyrophenones, thioxanthines and fluphenazine. Chlorpromazine and prochlorperazine produced inconsistent effects while clozapine and loxapine respectively delayed and prolonged the peak tremor response. While these findings support primary involvement of striatal dopaminergic mechanisms in LON 954 tremorogenesis, a reduction in cyclic AMP levels may be an important factor in the observed effects.
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PMID:Potentiation of LON 954 tremor by typical and atypical neuroleptics--an indication of striatal dopamine antagonism. 610 79

Budipine is a new 1-tertiary-butyl-diphenylpiperidine derivative with primarily central action. In animal experiments involving different pathological models, a pharmacological profile is found suggesting that budipine has therapeutic potential as antiparkinson drug. Besides a mild centrally stimulatory effect in the unprovoked animal, strong antagonistic effects are observed on tremorine- or N-carbamoyl-2-(2,6-dichlorophenyl)-acetamidine-hydrochloride (LON-954) induced tremor, and on cataleptic states elicited by haloperidol, reserpine, tetrabenazine and perphenazine. Attempts are made to elucidate tha mechanism of action in comparison with conventional clinical anti-parkinson drugs. The anticholinergic activity of budipine is too weak to explain its effectiveness. Direct dopamine receptor stimulation was excluded, but not the release of dopamine or reuptake inhibition. No clear influence was detectable on noradrenergic neurons either peripherally or centrally. An influence of serotoninergic mechanisms by way of reuptake inhibition and release, however, appears feasible. Peripheral effects are minimal. The possible advantages of budipine in the treatment of Parkinson's disease are discussed in comparison to the drugs used in therapy today.
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PMID:[Summarizing description of the pharmacology of budipine, a new 4,4-diphenylpiperidine derivative used in Parkinson therapy (author's transl)]. 719 25