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)

The role of glutamatergic (NMDA), cholinergic and purinergic neurotransmission in the pedunculopontine nucleus, red nucleus, ventrolateral thalamic nucleus, entopeduncular nucleus, and the substantia nigra in the development of the high pressure neurological syndrome (HPNS) was investigated in the rat. Focal injection of D-2-amino-7-phosphonoheptanoate (D-APH, 5 nmol per side) into the red nucleus or the pedunculopontine nucleus was protective against HPNS-induced convulsions. Carbachol (10 nmol), injected into the red nucleus, did not influence the severity of the symptoms of HPNS. Injection of carbachol into the pedunculopontine nucleus, significantly lowered the threshold pressure for convulsions and increased the threshold pressure for tremor. 2-Chloroadenosine (5 nmol), injected into the red nucleus, produced a potent antitremorgenic effect and a similar but less pronounced effect when injected into the pedunculopontine nucleus. 2-Chloroadenosine, injected into the substantia nigra (12.5 nmol) or the ventrolateral thalamic nucleus (25 nmol), facilitated the development of tremor and, in the entopeduncular nucleus (25 nmol), facilitated the occurrence of convulsions. These results show the complexity of neurotransmitter interactions in different regions of the brain, under high pressure. They also indicate that the biochemical and anatomical substrates, involved in the convulsions produced by HPNS, differ substantially from those in other experimental models of epilepsy.
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PMID:Brain nuclei and neurotransmitters involved in the regulation of the high pressure neurological syndrome in the rat. 168 3

The chronic administration of theophylline was studied in twenty patients with essential tremor in a double-blind cross-over trial. The tremor was improved significantly after four weeks of treatment. In mice the chronic administration of theophylline was compared with propranolol on the modulation by adenosine, 5-HT, (-)isoprenaline or GABA of NMDA-induced depolarisation of neocortical slices. Adenosine depolarisation was abolished by two-weeks treatment with theophylline but not propranolol. Potentiation by (-)isoprenaline of NMDA responses was reduced by theophylline (100 mg/kg/day) and propranolol treatment (25 mg/kg/day), but a lower dose of propranolol further increased it. The enhancement by 5-HT of NMDA-induced depolarisation was unaffected by the pretreatment with theophylline, while the higher dose of propranolol blocked it. GABA caused no significant change of NMDA depolarisation in control slices, but after theophylline treatment (100 mg/kg/day) and propranolol administration at both doses it significantly potentiated NMDA depolarisation. The enhancement of GABA sensitivity might be an important common factor in decreasing the essential tremor after propranolol and theophylline treatment.
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PMID:The effect of theophylline on essential tremor: the possible role of GABA. 194 76

Therapeutic efficacy of calcium channel blockers in stroke remains controversial, but previously used agents bind almost exclusively to L-type calcium channels. The newly-discovered N-type calcium channel is specific to neurons, and therapy involving blockade of this site has not been previously attempted. We assessed the neuroprotective effect of omega-conotoxin GVIA (CgTx), a blocker of N-type calcium channels, using both in vitro hypoxic injury to rat cortical neurons and an in vivo model of reversible spinal cord ischemia in the rabbit. In cell cultures, CgTx inhibited hypoxia-induced 45Ca accumulation and neuronal injury minimally, compared to the NMDA antagonist ketamine. In vivo, the duration of spinal cord ischemia which produced permanent paraplegia in 50% of control animals (ET50) was 24.0 +/- 2.6 min. Animals treated 2 h prior to ischemia with 0.5 nmol CgTx in the subarachnoid space had an ET50 of 26.9 +/- 1.8 min (P = 0.36). Animals treated 24 h prior to ischemia (all had persistent systemic tremor) had a ET50 of 28.9 +/- 1.8 min (P = 0.13). We conclude that pharmacologic modulation of the N-type calcium channel does not provide a significant protective effect against neuronal hypoxic-ischemic injury.
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PMID:Treatment with conotoxin, an 'N-type' calcium channel blocker, in neuronal hypoxic-ischemic injury. 208 77

We report the effect of focal injections of N-methyl-D-aspartate (NMDA, 5 nmol) and 2-amino-7-phosphonoheptanoate (APH, 5 and 10 nmol) into the ventrolateral thalamic nucleus on behavioural symptoms of the high pressure neurological syndrome in rats. The injection of NMDA significantly lowers the threshold pressure for tremor and increases its intensity. The injection of APH significantly increases the threshold pressure for tremor and decreases its intensity. APH, 10 nmol, significantly increases the threshold pressure for myoclonus and convulsions. These protective effects are, however, less pronounced than those produced by either systemic injection of APH or its focal infusion into the basal ganglia output system.
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PMID:Effect of NMDA and 2-amino-7-phosphonoheptanoate focal injection into the ventrolateral thalamic nucleus on the high pressure neurological syndrome in the rat. 215 22

According to the hypothesis that the development of physical dependence on and tolerance to opiates depends on the inhibition by opiates of L-asparaginase and L-glutaminase activities in the brain, and the blockade by opiates of the aspartatergic/glutamatergic receptors especially NMDA, four female and fourty-four male heroin addicts were included in a double-blind clinical trial. Four mg chlorpromazine (CPZ) was administered every hour and 10 mg diazepam (DIA) every 6 hours to a group consisting of two female and nineteen male inpatients. The remaining subjects received 15 mg non-opioid antitussive dextromethorphan (DM) instead of CPZ. The withdrawn addicts were controlled twice a day and yawning, lacrimation, rhinorrhoea, perspiration, goose flesh, muscle tremor, dilated pupils, anorexia, joint and muscle aches, restlessness, insomnia, emesis, diarrhea, craving and rejection of smoking as abstinence syndrome signs were observed and rated on a scale of 1, 2 and 3 points according to their intensity. All signs, except perspiration and emesis, were significantly less intense in the group given DM + DIA than CPZ + DIA. The other plus points included the immediate stop of craving and the early onset of smoking in DM + DIA group. The results are considered to be supporting evidence for the hypothesis emphasizing the blockade of NMDA receptors by opiates in opiate addiction. Furthermore, the decrease caused by non-opioid NMDA antagonists in the responsiveness of NMDA receptors appears very promising for the treatment of opiate addicts.
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PMID:The treatment of heroin addicts with dextromethorphan: a double-blind comparison of dextromethorphan with chlorpromazine. 218 2

Intracerebral injections of the broad spectrum excitatory amino acid antagonist kynurenic acid (50 ug) alleviated the symptoms of akinesia, tremor and rigidity in a severely parkinsonian monkey. Unilateral injection of kynurenic acid within the medial pallidal segment produced rotational behaviour away from the side of the injection, and the limbs on the contralateral side showed relief of the MPTP-induced parkinsonian symptoms. The subsequent bilateral injection of the excitatory amino acid antagonist allowed the monkey to move freely, unhindered by tremor or rigidity. In addition unilateral injections of the NMDA antagonist MK-801 (5, 25 and 50 ug) within the medial pallidum also produced dose-related rotational behaviour, with alleviation of parkinsonian symptoms in the contralateral limbs. Systemic administration of MK-801 (1 ng/kg - 1 ug/kg i.m.) was without effect.
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PMID:Injection of excitatory amino acid antagonists into the medial pallidal segment of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated primate reverses motor symptoms of parkinsonism. 225 May 73

Studies of pathogenetic mechanisms of myoclonus and spinal spasticity have established a strong association between deficient inhibitory glycinergic transmission and pathologic rigidity and tremor. Consistent with known cases in the clinical literature, electrophysiologic data from animal models of myoclonus implicate dysfunction of segmental spinal cord circuitry. The present study sought to further explore pathogenetic mechanisms at the circuit level. In vitro preparations of isolated spinal cord from neonatal rodents allowed for stable recordings of individual cells as well as populations of motoneurons. Blockade of glycine receptors enhanced 5- to 15-Hz sinusoidal oscillations that were synchronous in entire populations of motoneurons as well as along multiple segments of the spinal cord. Oscillations at motoneurons were mediated largely by non-NMDA excitatory synaptic inputs. Blockade of GABAA receptors, and not GABAB receptors, abolished sinusoidal oscillations, suggesting a critical role for GABAA receptors in the premotoneuronal circuitry responsible for generation or transmission of the sinusoidal oscillations. These data offer new insights into possible pathogenetic mechanisms of spinal myoclonus and may help guide future research leading to specific therapies for hyperkinetic movement disorders of spinal origin.
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PMID:Involvement of glycine and GABAA receptors in the pathogenesis of spinal myoclonus: in vitro studies in the isolated neonatal rodent spinal cord. 747 87

An in vitro system for the incubation of mediobasal hypothalami (MBH) of cockerels and a radioimmunoassay for chicken luteinising hormone-releasing hormone-I (cLHRH-I) were developed. The size of the hypothalamic fragment (MBH including the median eminence) and the incubation conditions used (40 degrees C, under constant shaking and gassing) preserved the physiological properties of the tissue. It was possible to maintain the MBH in vitro and to study the LHRH release for several hours. The assay proved sensitive enough (ED80 = 0.794 pmol/tube, ie 4.59 pg/ml) and sufficiently precise (within-assay coefficient of variation = 4.4% and between-assay coefficient of variation = 10.2%) to measure the amounts of peptide released in the incubation medium. The use of this incubation system provided the first evidence of the stimulating effect of the excitatory amino acids glutamate, NMDA and kainate on the secretion of cLHRH-I in birds. Our results suggest that the effect on the NMDA receptor is predominant.
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PMID:Release of chicken luteinising hormone-releasing hormone-I (cLHRH-I) by mediobasal hypothalamus in the cockerel: validation of an incubation system and effect of excitatory amino acids. 791 82

L-beta-N-methylamino-L-alanine (L-BMAA, 500 micrograms) infusions into the lateral ventricle induced splay, clonic convulsions, and rigidity in about 60% of rats. Electroencephalograph (EEG) recording during clonic convulsions and rigidity demonstrated epileptiform discharges. Duration and severity of L-BMAA-induced clonic convulsions were reduced significantly by DNQX, a non-NMDA glutamate receptor antagonist, but not by AP-5, a NMDA receptor antagonist or MK-801, a noncompetitive NMDA antagonist. Latency of L-BMAA-induced clonic convulsions was significantly prolonged by DNQX, AP-5 and MK-801. L-BMAA-induced splay was not modified by DNQX or AP-5 but was slightly enhanced by MK-801. L-BMAA-induced rigidity was abolished by MK-801 and partially inhibited by DNQX and AP-5. The L-BMAA-induced behaviors of grooming, facial tremor, etc. were affected by DNQX, AP-5, and MK-801. Our results suggest that L-BMAA may induce behavioral changes by acting upon several subtypes of excitatory amino acid receptors.
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PMID:L-beta-methylamino-alanine-induced behavioral changes in rats. 809 28

N-Methyl-D-aspartate (NMDA, 20 mg/kg) produced a clear decrease in mouse exploration in open parts of an elevated plus-maze. Paradoxically, 40 mg/kg NMDA did not modify the behavior of the mice in the plus-maze. NMDA at a dose of 80 mg/kg again depressed the exploratory activity of mice, but this effect was accompanied with tremor and compulsive tail biting. The 'anti-exploratory' dose of NMDA (20 mg/kg) increased, whereas the 'tremorigenic' dose (80 mg/kg) significantly decreased the number of cholecystokinin (CCK) binding sites in the mouse cerebral cortex. The competitive NMDA antagonist (+/-)-CPP (2.5-5 mg/kg) and the non-competitive antagonist MK-801 (0.25 mg/kg) antagonized the anti-exploratory effect of NMDA (20 mg/kg). The tricyclic antidepressant imipramine (5 mg/kg, but not 1 or 10 mg/kg) also attenuated the inhibition of exploratory activity induced by NMDA. Of three CCK receptor antagonists tested, the unselective CCK antagonist proglumide (1 mg/kg, but not 0.1 and 10 mg/kg) significantly opposed the anti-exploratory action of NMDA. The selective CCK antagonists L-365,260 (1 microgram/kg) and devazepide (1 microgram/kg) were evidently weaker antagonists of NMDA. Furthermore, 10 micrograms/kg of L-365,260, a CCK-B receptor antagonist, and 1 mg/kg of devazepide, a CCK-A receptor antagonist, even tended to augment the effect of NMDA in the plus-maze. The results of the present study seem to give some support to the notion that not only NMDA receptors, but also CCK-ergic mechanisms are involved in the modulation of anti-exploratory action of NMDA in the elevated plus-maze.
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PMID:Anti-exploratory effect of N-methyl-D-aspartate in elevated plus-maze. Involvement of NMDA and CCK receptors. 847 31


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