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)

1. The drug HA-966 (1-hydroxy-3-amino-pyrrolidone-2), which chemically resembles the cyclic form of GABA, has been studied for neuro-pharmacological properties and for effects on the catecholamine content of the corpus striatum.2. The acute effects on spontaneous behaviour of rodents included flaccid catalepsy and reversible tranquillization in doses which were 5% or less of the lethal dose. Long lasting depression of the CNS, followed by complete recovery, was produced in the cat and the dog. In the monkey HA-966 caused periodical sleeping episodes.3. The exploratory behaviour and the amphetamine-induced motor activity in mice were blocked by HA-966. The toxicity of amphetamine in aggregated mice was only moderately reduced, suggesting that HA-966 differs from neuroleptics.4. Tremors induced by chemical agents (nicotine, zinc and tremorine) were markedly inhibited by HA-966. The muscarinic effects of tremorine were not reduced by HA-966, indicating a selective central antitremor effect.5. HA-966 elevated the threshold to strychnine convulsions and abolished the ipsilateral flexor reflex, while not having motor endplate blocking properties. It is suggested that HA-966 depresses central internuncial neurones.6. In rats and rabbits HA-966 produced synchronous EEG and inhibited the sensory arousal in doses not causing sedation. In the monkey the drug caused a periodical dissociation between ;sleep-EEG' and behaviour.7. In rat brain, HA-966 selectively elevated the dopamine content in the corpus striatum, while no changes in noradrenaline and 5-hydroxytryptamine contents could be demonstrated. The effect was still present when dopa synthesis was inhibited with alpha-methyl-p-tyrosine.8. Several effects of intravenously administered HA-966 became manifest after an appreciable delay and in hepatectomized mice the effects were much reduced. It is postulated that HA-966 is converted to a pharmacologically active metabolite.9. The results are discussed in the light of current views on drug therapy in extrapyramidal conditions and a GABA-related hypothesis as to the mode of action of HA-966 is presented.
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PMID:1-Hydroxy-3-amino-pyrrolidone-2(HA-966): a new GABA-like compound, with potential use in extrapyramidal diseases. 515 20

1. In rats the effect of drugs on oxotremorine tremor and oxotremorine-induced increase in brain acetylcholine has been investigated.2. Reserpine, (+/-)-alpha-methylmetatyrosine and diethyldithio-carbamic acid, drugs which have in common the ability to decrease tissue noradrenaline concentration, inhibited oxotremorine tremor without preventing the oxotremorine-induced increase in brain acetylcholine.3. (+/-)-p-chlorophenylalanine, a depletor of tissue 5-hydroxytryptamine, did not inhibit oxotremorine tremor.4. Phenoxybenzamine and propranolol inhibited oxotremorine tremor, and propranolol was without effect on oxotremorine-induced increase in brain acetylcholine.5. The toxicity of oxotremorine was increased by reserpine and phenoxybenzamine.6. The significance of these findings is discussed with regard to the mode of action of oxotremorine.
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PMID:Effects of drugs on tremor and increase in brain acetylcholine produced by oxotremorine in the rat. 541 85

The effects of clomipramine HCl (15 mg kg-1 i.p.) on behaviour, body temperature and brain amines were investigated in rats that had been chronically treated twice daily with increasing doses of delta 9-tetrahydrocannabinol (delta 9-THC, 2-6 mg kg-1 i.v.). delta 9-THC produced a biphasic change in behaviour, stimulation followed by depression, and a pronounced hypothermia. Tolerance developed rapidly to these effects of delta 9-THC. Chronic treatment with delta 9-THC reduced the levels of homovanillic acid, 5-hydroxytryptamine and noradrenaline. The level of dopamine was not altered with chronic treatment and tolerance appeared to develop to the increased levels of 5-hydroxyindoleacetic acid induced by delta 9-THC. Injection of clomipramine, 12-14 h after 2, 5 or 10 days of delta 9-THC treatment induced characteristic changes in the rats behaviour which consisted of writhes, backward kicking, wet shakes, jumps ataxia and front paw and whole body tremor. The severity of the behavioural changes appeared to be dependent on the period of delta 9-THC administration and they were not accompanied by a change in body temperature or consistent changes in brain amines or metabolites. The results indicate that physical dependence on delta 9-THC may occur since clomipramine is able to precipitate changes in behaviour, indicative on an abstinence syndrome, in rats chronically treated with delta 9-THC. It is suggested that tryptaminergic mechanisms are altered during chronic delta 9-THC treatment and that clomipramine induces the behavioural changes by interacting with an altered tryptaminergic system.
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PMID:Time-course of the effects of chronic delta 9-tetrahydrocannabinol on behaviour, body temperature, brain amines and withdrawal-like behaviour in the rat. 612 98

Five vervet monkeys were administered increasing doses (4--12 mg/kg/day) of d-amphetamine over a period of 35 days. Three phases od behavioural change were discerned: phase 1 during which animals exhibited repetitive stereotyped action sequences with rapid head movements, occasional abnormal grooming, picking at the cage, hand-staring and snatching; phase 2 in which behaviour became progressively more restricted and animals became markedly unresponsive to auditory, visual and tactile stimuli; phase 3 was characterised by the abrupt development of gross over-responsiveness to environmental stimuli, ataxia and tremor. At post-mortem, by comparison with controls, amphetamine-treated monkeys showed marked depletions of the monoamines dopamine (DA), noradrenaline (NA) and serotonin (5-HT) in corpus striatum and cerebral cortex and reductions in the activities of tyrosine hydroxylase and dopa decarboxylase in striatum. Turnover of these monoamines, assessed by high-performance liquid chromatography determinations of their respective metabolites, was also reduced. These findings are interpreted as evidence of monoamine neurone destruction, most severely in the case of DA neurones. Though there was a non-significant reduction in 3H-spiperone binding (reaching almost 50% in nucleus accumbens), numbers of receptors for the monoamines nA and 5-HT were not significantly changed, and the activities of the enzymes choline acetyltransferase and glutamine decarboxylase were similar in experimental and control animals. The contrast of these findings with those seen in post-mortem brains in schizophrenia is discussed.
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PMID:Behavioural and biochemical effects of chronic amphetamine treatment in the vervet monkey. 613 May 56

Pharmacological and biochemical data on trazodone are reviewed in order to compare this drug to imipramine and other tricyclics both from the point of view of the mechanism of action and preferential clinical indications. Trazodone tends to inhibit biochemical and pharmacological functions depending on the catecholaminergic system, whereas imipramine has a potentiating activity. However, both these drugs decrease the density of beta-receptors following repeated administrations. Trazodone and imipramine have similar effects on the serotoninergic system. The two drugs also share an antinociceptive activity. It is stressed that this activity has been of critical importance in the discovery of trazodone. In fact, the development of this drug was based on the working hypothesis that a disturbance in the perception of unpleasant experience has a role in the pathogenesis of depression. Some medical implications of the alpha-blocking activity of trazodone are discussed. Trazodone is preferable to other antidepressant treatment when depression is associated with angle-closure glucoma, cardiovascular disturbances depending on noradrenaline release, tremor, some psychotic conditions and alcoholism.
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PMID:Trazodone, a new avenue in the treatment of depression. 614 38

3-methoxy-4-hydroxyphenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA) as well as homovanillic acid (HVA) and cyclic AMP were estimated in the morning urine of 41 drug-free parkinsonian patients and 25 hospitalized controls. In 29 patients, the estimations were repeated after 2 weeks treatment with L-dopa plus decarboxylase inhibitor. Drug-free patients excreted more MHPG and less 5-HIAA than controls. The difference from controls was significant for MHPG, only for the subgroup of patients with akinesia as the main symptom (P = 0.001) and for 5-HIAA only for the tremor subgroup (P = 0.03). 2 weeks treatment with L-dopa plus decarboxylase inhibitor, increased the MHPG excretion significantly only for the akinesia subgroup, where the pretreatment MHPG values were high, while there was no change in MHPG excretion in the tremor and the rigidity subgroups. The treatment caused no change in the 5-HIAA excretion in the tremor subgroup, where the pretreatment values were low, while in the rigidity and akinesia subgroups 5-HIAA excretion was significantly decreased. These results, as well as our previous results on HVA and cyclic AMP, show that there are considerable differences among the subgroups of parkinsonian patients regarding the metabolism of dopamine, noradrenaline and serotonin.
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PMID:Urinary noradrenaline and serotonin metabolites in drug-free Parkinson patients and the effect of L-dopa treatment. 618 30

In an attempt to elucidate the mechanism of wet dog shakes (WDS) produced by carbachol administered into the rat lateral brain ventricle, the effects of blockade of muscarinic and nicotinic receptors on shaking response and the effects of carbachol on central catecholaminergic, serotonergic (5-HT) and GABAergic functions were studied in rats. The muscarinic receptor antagonists, atropine and scopolamine attenuated WDS produced by carbachol, whilst a peripherally active muscarinic receptor antagonist, scopolamine methyl nitrate, failed to influence WDS. The nicotine antagonist, mecamylamine, did not affect WDS caused by carbachol either. Carbachol dose dependently decreased brain concentration of noradrenaline (NA) but failed to affect the concentration of dopamine (DA). While the brain concentration of 5-HT was unchanged, the concentration of 5-hydroxyindoleacetic acid (5-HIAA) was increased in a dose-related manner. The catecholamine turnover times were unaffected whereas 5-HT turnover time was significantly prolonged. Atropine, but not mecamylamine, prevented the decrease in brain NA induced by carbachol. Consequently, the carbachol-induced enhancement in the level of 5-HIAA was completely blocked by atropine and only slightly influenced by mecamylamine. Neither brain GABA concentration nor glutamic acid decarboxylase activity were affected by carbachol. Behavioral and biochemical data suggest that WDS produced by carbachol may be mediated through the stimulation of central muscarinic receptors. The anatomical localization and exact mechanism of carbachol-induced WDS remain to be elucidated.
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PMID:Studies on the mechanism of wet dog shakes produced by carbachol in rats. 620 Aug 91

Noradrenaline (NA), methoxamine, dopamine (DA), given intracerebroventricularly (ICV), and L-DOPA, administered systemically, significantly blocked wet dog shakes (WDS) produced by carbachol chloride (10 microgram/10 microliter, ICV) in rats. Reserpine, alpha-methyl-p-tyrosine and FLA 63 did not affect WDS, while diethyldithiocarbamic acid depressed it. Aceperone and yohimbine weakened shaking response to carbachol but phentolamine given ICV showed no effect on WDS. Propranolol and isoproterenol administered ICV did not significantly influence WDS. Apomorphine failed to affect WDS induced by carbachol. Pimozide and spiperone were also ineffective against WDS, but amphetamine and metoclopramide efficiently blocked it. Selective depletion of brain NA concentration considerably enhanced WDS, while selective depletion of brain DA concentration failed to affect it. These results suggest that carbachol-induced WDS behavior is under the inhibitory control of noradrenergic neurons.
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PMID:The involvement of catecholaminergic mechanisms in the appearance of wet dog shakes produced by carbachol chloride in rats. 628 Jun 27

4-aminopyridine is the first of the aminopyridines to be used in clinical practice. It blocks potassium channels and thereby increases acetylcholine, and possibly noradrenaline, release at nerve terminals. In man the drug has a significant action at the neuromuscular junction, but has little effect on the autonomic nervous system or muscle (smooth, skeletal, or cardiac) although such actions have been demonstrated in animals. It may be clinically useful in the reversal of nondepolariser blockade and a role in antibiotic associated block has been proposed. It may be used effectively as an analeptic agent. It appears to be a useful therapeutic agent in myasthenia gravis and Eaton Lambert syndrome, although of limited use in botulism. It effects on the central nervous system are considerable. These account for the major side effects of the drug which include tremor, excitability and convulsions.
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PMID:4-aminopyridine-a review. 628 56

We studied the effect of posture on the sympathoadrenal response to intravenous theophylline in six normal subjects. On three separate occasions they received an intravenous infusion of either theophylline (6 mg/kg) while supine, theophylline (6 mg/kg) while standing or saline as placebo while standing. With the subjects standing theophylline caused tremor, a peak heart rate of 99 +/- 6 beats/min, and an elevation of plasma cyclic AMP from 9.3 +/- 0.7 to 15.1 +/- 1.7 nmol/1 (mean +/- s.e. mean). There was a small, but significant, elevation of plasma adrenaline, noradrenaline and glucose. The elevation in plasma catecholamines was insufficient to explain either the sympathomimetic effects of theophylline or the rise in plasma cyclic AMP. Theophylline had little or no effect with the subjects supine. The mean peak theophylline concentration following infusion was significantly higher with the subjects upright than when supine (18.3 c.f. 12.4 mg/l, P less than 0.025). However, adequate plasma levels of theophylline were obtained in all subjects when lying or supine. Analysis of individual data suggests that differences in plasma levels of theophylline are unlikely to account for the increased effects seen on standing. The mechanism of action of theophylline cannot be explained by increased secretion of catecholamines alone. Theophylline appears to amplify the increased sympathetic activity associated with standing and this is probably by phosphodiesterase inhibition.
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PMID:The effect of posture on the sympathoadrenal response to theophylline infusion. 631 28


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