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)

The influence of clonidine on the toxicity produced by two irreversible, organophosphate cholinesterase inhibitors, soman and echothiophate, was studied in mice. At lethal doses, soman produced whole body tremor but no muscle fasciculation; at lethal doses, echothiophate produced muscle fasciculations but no whole body tremor. Pretreatment with clonidine protected against several toxic manifestations of soman, but had little effect on echothiophate toxicity. In addition to its documented effects on acetylcholine metabolism, clonidine was found to be a weak inhibitor of acetylcholinesterase. At certain concentrations, clonidine protected the enzyme from permanent inactivation by soman. These findings indicate that the toxicity of soman and echothiophate reflect primarily central and peripheral actions, respectively, and that clonidine has a much greater protective effect versus the centrally-acting agent. Moreover, direct interactions with acetylcholinesterase may contribute to clonidine protection from cholinesterase inhibitor toxicity.
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PMID:Clonidine protection from soman and echothiophate toxicity in mice. 378 71

The acute effects of diisopropylfluorophosphate (DFP) were assessed in DBA/2Ibg, C57BL/6Ibg and C3H/2Ibg mice. The DFP was administered by intraperitoneal injection in saline. Brain acetylcholinesterase (AChE) activity was maximally inhibited within 5 min after injection. All mice showed signs of organophosphate intoxication including salivation, lacrimation, diarrhea, respiratory distress, tremor and, at high doses, seizures. The C57BL mice were most susceptible to these effects of DFP. The LD50 values for DFP were 8.0, 7.6, and 6.8 mg/kg for male DBA, C3H, and C57BL mice, respectively. The LD50 values for females were nearly the same. Body temperature and brain AChE activity decreased in a dose-dependent manner following injections of DFP of 3.17, 4.22, 5.28, and 6.33 mg/kg. Maximum temperature depression occurred 2 hours after DFP administration; by 24 hours temperatures had returned to normal except for C57BL mice treated with the highest dose of DFP. The C57BL strain was most susceptible to the DFP-induced hypothermia, the C3H strain was the most resistant, and the DBA strain was intermediate. Maximum temperature depression and residual AChE activity, as measured 24 hours after injection, were linearly related. These strain differences do not seem to be explained easily by a differential inhibition of AChE activity.
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PMID:Genetically determined differences in acute responses to diisopropylfluorophosphate. 399 71

Using experimental models of parkinsonism, imitating the hypertonus of the parasympathetic system (hypokinesia, rigidity and tremor) following the intraperitoneal injection of the acetylcholinesterase inhibitor galanthamin (15 mg/kg) to mice, the authors showed that the m-cholinoblocker metamisyl (2 mg/kg) blocks all manifestations of the CNS parasympathetic hypertonus whereas the n-cholinoblocker eterofen (30 mg/kg) increases them. Based on the theory developed by the authors as to the reciprocity of interaction between the m- and n-cholinergic mechanisms within the framework of the single cholinergic system of the body, they offered the treatment of parkinsonism by the combined use of metamisyl (1-2 mg) and galanthamin (5-10 mg). Forty-five patients were treated with metamisyl alone and 40 patients with metamisyl coupled with galanthamin. The latter method of treatment proved to be more effective. The patients responded to the treatment immediately. It lasted 2-4 weeks. The follow-up showed that in some patients, the effect of the treatment stabilized and persisted for 4 weeks to 12 months without the use of the antiparkinsonian drugs. The authors emphasize that in cases of parkinsonism it is necessary to study and take into account the nature of changes in both intersystemic mediator interaction (between ACh and NA, ACh and D, ACh and 5-HT, etc.) and the intrasystemic one (between m- and n-cholino, alpha- and beta-adreno, D1 and D2, 5-HT1 and 5-HT2-ergic mechanisms).
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PMID:[Method of treating parkinsonism with metamizil in combination with galanthamine (clinico-experimental basis)]. 399 98

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

Scopolamine was either continuously infused or injected once daily into C3H mice. Chronic infusion resulted in mice that were supersensitive to the hypothermia and tremor produced by the muscarinic agonist, oxotremorine. Chronic scopolamine infusion did not alter brain acetylcholinesterase (AChE) or choline acetyltransferase (ChAT) activities but it did produce an increase in brain muscarinic receptors, as measured by quinuclidinyl benzilate (QNB) binding. The maximal increase in QNB binding was seen at the 0.2 mg/kg/hr dose. Further increase in dose resulted in a return to control QNB binding in all brain regions studied except cortex. These animals were still supersensitive to oxotremorine, suggesting a dissociation between receptor number and response to agonist. Animals injected once daily for 10 days with 5 mg/kg exhibited an increase in QNB binding while no increase was seen at 20 mg/kg/day. Chronic oxotremorine infusion resulted in tolerance to the hypothermia-producing effects of oxotremorine. This was accompanied by a decrease in brain QNB binding. Coinfusion of scopolamine with oxotremorine blocked both the tolerance development and receptor changes. These experiments demonstrate that chronic scopolamine treatment can elicit an increase in brain muscarinic receptors which is accompanied by supersensitivity to agonists. However, this effect is not clearly dose related, and a strict relationship between receptor number and agonist response does not exist.
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PMID:Chronic scopolamine treatment and brain cholinergic function. 673 17

The development of tolerance to cholinergic agonists such as oxotremorine is a well established phenomenon. The hypothesis that such tolerance may be explained by a decrease in the number of affinity of muscarinic receptors was tested by chronically treating C3H mice with oxotremorine. Chronic treatment was achieved by continuously infusing oxotremorine via an indwelling i.v. catheter. Doses ranged from 0.03 to 1.0 mg/kg/hr. Clear tolerance was observed in that symptoms such as salivation, lacrimation and muscle tremor decreased or disappeared during the infusion period. Similarly, chronically treated animals exhibited minimal hypothermia or impairment of rotarod performance when challenged with an oxotremorine dose which significantly depressed both of these measures in naive animals. The activities of the enzymes, acetylcholinesterase and choline acetyltransferase, as well as the binding of [3H]-3-quinuclidinyl benzilate in seven brain regions, were assessed. Chronic oxotremorine treatment failed to alter acetyltransferase activity in any of the brain regions. Choline acetyltransferase activity was only marginally decreased in several brain regions. A significant decrease in maximal [3H]-3-quinudidinyl binding was observed in six of the regions examined. No alteration in [3H]-3-quinuclidinyl affinity was detected. Tolerance to oxotremorine was detected at doses which failed to alter choline acetyltransferase activity or receptor number. These data support the observations of others who noted that chronic muscarinic stimulation results in a decrease in muscarinic receptors, but suggest the importance of mechanisms other than decreased receptor number in early stages of tolerance development.
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PMID:Cholinergic adaptations to chronic oxotremorine infusion. 725 34

The interrelationships were studied between catecholaminergic and cholinergic systems in 169 patients with extrapyramidal system diseases: 68 patients with torsion dystonia (58 with the rigid form and 10 with the hyperkinetic form), 10 with Hallervorden-Spatz disease, 61 with hepatolenticular degeneration, and in 40 with idiopathic tremor. The secretion of dopamine (DA), noradrenaline (NA), adrenaline (A) and their precursor--DOPA) as well as the activity of acetylcholinesterase (AChe)--the enzyme disintegrating acetylcholine--were determined. In the rigid form of torsion dystonia and in Hallervorden-Spatz disease reduced secretion of all catecholamines (mainly DA) and DOPA was observed, with decreased AChE activity. In the hyperkinetic form of torsion dystonia the secretion of DA was increased and AChE activity was higher. In the patients with idiopathic tremor the secretion of A and NA was decreased and AChE activity was reduced. In patients with hepatolenticular degeneration the secretion of NA and DA was decreased and that of their immediate precursor DOPA was increased. Changes of AChE activity showed a wide range. The observed disturbances reflect various forms of disturbances in the equilibrium between the catecholaminergic and cholinergic systems which are one of the leading pathogenetic mechanisms in the development of various extrapyramidal syndromes.
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PMID:[Characteristics of central neurotransmitter metabolism in hereditary extrapyramidal disorders]. 732 5

Six patients who developed extrapyramidal manifestations following poisoning with the organophosphorus (OP) insecticide fenthion are reported. The extrapyramidal features, in order of frequency, were dystonia, rest tremor, cog-wheel rigidity, and choreo-athetosis. The delay in onset of these signs, following poisoning, varied from 4 to 40 days, and they disappeared spontaneously in about 1 to 4 weeks in those who survived. The human extrapyramidal system is rich in cholinergic neurons and acetylcholinesterase (AChE). Inhibition of AChE by fenthion, which has ready access to central neurons on account of its lipid solubility, is postulated as the mechanism underlying the extrapyramidal manifestations.
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PMID:Extrapyramidal manifestations complicating organophosphorus insecticide poisoning. 757 21

A case in which SPECT brain imaging was used in the diagnosis and treatment of chronic effects from acute acetylcholinesterase inhibitor poisoning is presented. The patient was exposed to an insecticide mixture containing phosphorothiate, pyrethrin, piperonyl butoxide, and petroleum distillates, which produced symptoms consistent with acute acetylcholinesterase inhibitor poisoning as well as an upper respiratory tract irritant. Delayed sequelae of gross neurologic symptoms followed, that is, coarse tremor, intermittent hemiballistic movements of the right arm and leg, flaccid muscular tone, fasciculations of muscle groups, muscle cramps, and sensory disturbances. A brain single-photon emission computerized tomography (SPECT) scan was performed 34 mo postexposure, revealing significantly decreased blood flow to the left temporal lobe and to the right and left basal ganglia. The patient's paresthesias were treated with phenytoin, which resulted in worsening of her movement disorder. A trial of amantadine and selegiline (Deprenyl) resulted in a dramatic reduction in dysfunctional movements and ataxia. Post amantadine and selegiline therapy, brain SPECT images revealed significantly improved blood flow with minimally decreased blood flow to the right and left basal ganglia. The use of SPECT scan techniques helped to elucidate objective chronic central nervous system effects subsequent to an acute insecticide exposure and also assisted in the evaluation of the effectiveness of therapeutic intervention.
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PMID:Evaluation of chronic neurological sequelae after acute pesticide exposure using SPECT brain scans. 812 50

Hypothermia and tremor responses of oxotremorine and eserine were studied in rats after several T3 treatment regimens. The T3 antagonized oxotremorine-induced hypothermia and failed to antagonize eserine hypothermic effect, but potentiated oxotremorine- and eserine-induced tremors. Acetylcholinesterase activity was not altered in T3 rats. The hypothetical mechanisms to explain changes of central cholinergic responses caused by T3 are discussed.
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PMID:Triiodothyronine (T3) modifies cholinergic-induced hypothermia and tremor in rats. 827 52


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