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)

Cholinesterase inhibitors vary in their selectivity for acetylcholinesterase versus butyrylcholinesterase. We examined several cholinesterase inhibitors and assessed the relative role of acetylcholinesterase versus butyrylcholinesterase inhibition in central and peripheral responses to these medications. Donepezil and icopezil are highly selective for acetylcholinesterase, whereas tacrine and heptylphysostigmine demonstrated greater potency for butyrylcholinesterase over acetylcholinesterase. All four compounds increased acetylcholine levels in mouse brains. Dose-response curves for tremor (central effect) and salivation (peripheral effect) showed that donepezil and icopezil possess a more favourable therapeutic index than the nonselective inhibitors, tacrine and heptylphysostigmine. Co-administration of the selective butyrylcholinesterase inhibitor tetraisopropylpyrophosphoramide (iso-OMPA) potentiated peripheral, but not central, effects of the selective acetylcholinesterase inhibitor icopezil. The improved therapeutic index observed in mice with icopezil is due to a high degree of selectivity for acetylcholinesterase versus butyrylcholinesterase, suggesting that high selectivity for acetylcholinesterase may contribute to the clinically favourable tolerability profile of agents such as donepezil in Alzheimer's disease patients.
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PMID:Pharmacology of selective acetylcholinesterase inhibitors: implications for use in Alzheimer's disease. 1475 2

Parkinson's disease (PD) is a chronic neurodegenerative disease, in which mainly dopaminergic neurons in the substantia nigra in the brain degenerate, leading to a depletion of dopamine (DA) in the striatum. The most important motor disturbances of the disease are bradykinesia (slowing down of movement), hypokinesia (poverty of movement), rigidity (muscle stiffness), tremor and postural instability. Besides these well-known motor symptoms, non-motor symptoms may develop, such as depression, cognitive impairment and psychosis. Psychotic symptoms constitute a relatively common but nevertheless serious complication, with visual hallucinations and paranoid delusions often being most prominent. These symptoms are important contributors to patient and caregiver distress and are often important risk factors for nursing home placement. Exogenous (related to therapeutic interventions) factors are of major importance but endogenous (related to the disease process itself) factors might also contribute to the development of psychotic symptoms in PD. Therapeutic strategies comprise reduction of antiparkinsonian treatment, cholinesterase inhibitors and atypical antipsychotics. As psychotic symptoms in PD are often influenced by both endogenous and exogenous factors, a combination of strategies may be chosen.
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PMID:Psychotic symptoms in Parkinson's disease: pathophysiology and management. 1515 49

Acute administration of the acetylcholinesterase inhibitor tacrine to rats induces tremulous jaw movements which can be used as a valuable model of parkinsonian tremor. In the present study, the number of tremor episodes and jaw movements were evaluated to assess the effects of the selective A2A antagonists SCH 58261 and SCH BT2 on tremorgenesis. SCH 58261 dose-dependently, and maximally at 5 mg/kg, reduced the number of both tremor episodes (-35%) and jaw movements (-50%), induced in rats by tacrine (2.5 mg/kg ip). Since adenosine A2A receptors are largely expressed throughout the striatum, chronic cannulae were implanted in the rat dorsomedial (DMS) and ventrolateral striatum (VLS) to investigate whether A2A antagonists could act at this level. Infusion of SCH BT2 (5 microg/microl), a water-soluble analogue of SCH 58261, in VLS antagonized both tremor episodes (-68%) and jaw movements (-76%) elicited by tacrine (2.5 mg/kg ip), whereas SCH BT2 infusion in DMS was less effective in blocking jaw movements (-50%) and did not significantly affect the number of tremor episodes. Taken together, the results of this study indicate that A2A antagonists effectively reduce the magnitude of tremulous jaw movements induced in rats by acute tacrine, mainly by an action in VLS and suggest that A2A antagonists might be used as specific agents against parkinsonian tremor.
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PMID:Blockade of adenosine A2A receptors antagonizes parkinsonian tremor in the rat tacrine model by an action on specific striatal regions. 1529 48

We describe 4 cases of delayed extrapyramidal disorder following acute dichlorvos poisonings. All patients were seriously poisoned since all exhibited profound coma and respiratory failure, and they were all tracheally intubated and mechanically ventilated. On admission, plasma cholinesterase activity was greaty decreased, < 10 micromol/ml/h at 37 C in all patients (< 10% of normal for our laboratory). Extrapyramidal symptoms occurred between 5 and 15 d and were characterized by dystonia of arms and legs, resting tremor, cogwheel rigidity, and hypereflexia. With bromocriptine therapy the features of extrapyramidal syndrome disappeared progressively with complete recovery in all patients. Our observations suggest a delayed extrapyramidal syndrome should be taken into account during the course of acute dichlorvos organophosphate poisonings.
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PMID:Extrapyramidal syndrome as a delayed and reversible complication of acute dichlorvos organophosphate poisoning. 1530 89

Nerve agent poisoning is characterized by the rapid progression of toxic signs, including hypersecretions, tremor, convulsions and profound brain damage. In the political arena of today's world, the threat of nerve agent use against military troops has prompted armies to search for prophylactic protection. The two main strategies for prophylaxis include biological scavengers that can bind or cleave nerve agents before they react with acetylcholinesterase, and antidotes as prophylactic treatment. Pyridostigmine is the current pretreatment for nerve agent poisoning and is in use by most of the armed forces in Western countries. However, since pyridostigmine barely crosses the blood-brain barrier it provides no protection against nerve agent-induced central injury. Pyridostigmine is ineffective when administered without post-exposure treatment adjuncts. Therefore, other directions for prophylactic treatment should be explored. These include combinations of carbamates (reversible AChE inhibitors) and central anticholinergics or NMDA receptor antagonists, benzodiazepines or partial agonists for benzodiazepine receptor, and other central AChE inhibitors approved for Alzheimer's disease. The transdermal route is an alternative way for delivering the prophylactic agent. Administration of prophylaxis can be extended also for civilian use during wartime.
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PMID:Pharmacologic prophylaxis against nerve agent poisoning. 1579 66

Tacrine is a potent and reversible inhibitor of acetylcholinesterase (AChE) in the brain. It produces tremor in animals, which is believed to be due to an increase in the brain acetylcholine level following AChE inhibition. The present study was undertaken to investigate the involvement, if any, of biogenic amines in the genesis of this motor dysfunction. Administration of tacrine (10-20 mg/kg, i.p.) produced dose- and time-dependent tremor in Balb/c mice. While in vivo inhibition of striatal AChE activity was observed only for the highest dose of tacrine, a dose-dependent increase in striatal choline acetyltransferase activity was obtained. Serotonin (5-HT) levels, as assayed following a sensitive HPLC-electrochemical procedure, were significantly increased in nucleus caudatus putamen, nucleus accumbens, substantia nigra, nucleus raphe dorsalis, olivary nucleus and the cerebellum. However, dopamine or norepinephrine levels remained unaltered in these areas of the brain. In animals treated with p-chlorophenylalanine, a specific tryptophan hydroxylase inhibitor and 5-HT depletor, tacrine failed to elevate the levels of 5-HT in the brain regions, and significantly attenuated tremor response to the drug. Tacrine-induced tremor was also significantly (83%) attenuated by 5-HT(2A/2C) receptor antagonist mianserin (5 mg/kg, i.p.), but methysergide (5 mg/kg, i.v.) could block tacrine-induced tremor only by 20%. Atropine (5 mg/kg, i.p.) antagonized tacrine-induced tremor by about 53%, but a combination of atropine and mianserin completely blocked the tremor response. These results indicate that the cholinergic tremor produced by tacrine in Balb/c mice is mediated via central serotonergic mechanisms, and stimulation of 5-HT(2A/2C) receptors plays a pivotal role in this motor dysfunction.
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PMID:Evidence for the involvement of central serotonergic mechanisms in cholinergic tremor induced by tacrine in Balb/c mice. 1599 Jan 78

Preclinical evidence strongly indicate that adenosine A(2A) receptor antagonists represent a promising class of drugs for the treatment of motor deficits associated to Parkinson's disease. The effects of adenosine A(2A) receptor antagonists were here assessed in a rat model of parkinsonian tremor induced by cholinomimetic drugs by evaluating the counteraction of tremulous jaw movements. Systemic administration of the A(2A) antagonist SCH 58261 dose-dependently reduced the magnitude of perioral tremor induced by the acetylcholinesterase inhibitor tacrine (2.5 mg/kg). Furthermore, intrastriatal infusion of SCH BT2 (5 microg/microl), a water-soluble analogue of SCH 58261, antagonized tacrine-induced jaw movements with a maximal effect in the ventrolateral striatum. On the other hand, SCH 58261 (5 mg/kg) was ineffective in blocking tremulous jaw movements stimulated by the direct muscarinic agonist pilocarpine (1 mg/kg). Taken together, these results indicate that A(2A) antagonists reduce parkinsonian tremor stimulated in rats by tacrine and that the striatum is deeply involved in the observed effect. Moreover, the ineffectiveness of SCH 58261 in blocking pilocarpine-stimulated perioral tremor suggests that the antitremorigenic effects of A(2A) antagonists described here are not related to a direct action on muscarinic receptor. The prospective of providing additional antitremor benefits considerably enhances the therapeutic potential of A(2A) antagonists.
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PMID:Dopamine and adenosine receptor interaction as basis for the treatment of Parkinson's disease. 1678 Aug 90

A novel method was described for detection carbamate pesticides residue in cucumber by immobilizing acetylcholinesterase enzyme in a micro-screen plate with 96 wells based on GA-BSA-gelatin gels. The concentrations of BSA, GA and gelatin in enzyme immobilization solution were optimized and the best concentrations were 5%, 0.5% and 0.1%, respectively. To analyze the pesticides residue 5g cucumber sample was homogenized with 10 mL acetone then an aliquot of 5mL extract was collected in a 10 mL test tube with a cap, into which 2g sodium chloride and 2mL dichloromethane were added in sequence. After shaking, 1 mL of the supernatant aliquot was evaporated by a blower in a small beaker and dissolved by 20% methanol-water solution then 50 microL was piped to a sample well. After incubation 10 minutes the absorbance was detected. The proposed method offered a rapid, simple and inexpensive means to in screen of batch samples. The minimum detection limit of this method was in a range of 0.1-0.2 mg/kg for cucumber samples.
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PMID:[Detection carbamate pesticides residue in cucumber by immobilized acetyicholinesterase enzyme]. 1688 32

We evaluated the effects of low-level inhalation exposures (whole body, 60min duration) to the chemical warfare nerve agent VX (0.016, 0.15, 0.30 or 0.45mg/m(3)) in rats. The range of concentrations was approximately equivalent to 0.02-0.62 times 1.0 LC50. Biochemical effects were assessed by evaluating blood acetylcholinesterase (AChE) activity and by a regeneration assay that quantified the amount of VX (as the G analog) present in blood. Behavioral effects were assessed using a variable-interval 56-s schedule of reinforcement (VI56), in which rats were trained to press a lever to receive a food reward. VI56 training was established before exposure and evaluations continued after exposure. Additionally, after exposure, acquisition and maintenance of an eight-arm radial maze (RAM) task was evaluated in which rats learned to locate the four arms of the maze that presented a single food pellet reward. Behavioral assessments were conducted over approximately 3 months following exposure. Transient miosis was observed following exposure to all concentrations of VX and exposures to the 0.45mg/m(3) concentration also produced mild and temporary signs of toxicity (i.e., slight tremor and ataxia) in some subjects. All concentrations of VX also inhibited circulating AChE and the highest concentration inhibited AChE activity to less than 10% of pre-exposure values. Regenerated VX-G was found in red blood cell (RBC) and plasma blood fractions. In this respect, more VX-G was seen in plasma than RBC. Only small disruptions were observed on the VI56 or RAM following some VX exposures. In general, however, behavioral effects were minor and not clearly systematic. Taken together these results demonstrate that largely asymptomatic exposures to VX vapors in rats can produce substantial biochemical effects while having only minor performance effects on a previously learned behavioral task and on the acquisition of a new behavioral task.
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PMID:Behavioral and biochemical evaluation of sub-lethal inhalation exposure to VX in rats. 1723 19

Parkinson's disease (PD) is a chronic, neurodegenerative disease with degeneration of the central dopaminergic neurons in the substantia nigra, leading to a depletion of dopamine (DA) in the striatum. This depletion causes the clinical hallmarks of this disease: bradykinesia, hypokinesia, rigidity, tremor and postural instability. Besides these well known motor symptoms, non-motor symptoms may develop, such as hyposmia, sleep disorders, autonomic disturbances, depression, cognitive impairment and psychosis. Pathophysiological mechanisms underlying these symptoms not only comprise Lewy body pathology in the central dopaminergic system, but also in the noradrenergic, serotinergic and cholinergic transmittersystems. Indeed, in Parkinson's disease, about 30-40% of the patients suffers fluctuating psychotic symptoms, mainly paranoid delusions and/or visual or acoustic hallucinations, symptoms considered to represent major contributors to patient and caregiver distress and nursing home placement. Endogenous (related to the disease process itself) as well as exogenous (related to therapeutical interventions) psychotogenic factors may contribute to the development of psychotic symptoms in PD. Therapeutical strategies, therefore, are aimed to reduce both endogenous and exogenous factors. To reduce endogenous psychotogenic factors, cholinesterase inhibitors, suggested to reduce cognitive deterioration, now seem to be the drugs of choice. In exogenously induced psychotic symptoms, atypical antipsychotics are considered the most effective. However, as psychotic symptoms in PD are often influenced by both endogenous and exogenous factors, a combination of both strategies may be preferred.
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PMID:PD-related psychosis: pathophysiology with therapeutical strategies. 1744 13


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