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 inferior olive of the cat has, with fluorescence histochemistry, been shown to receive a rich serotoninergic innervation. The distribution of this innervation agrees with the topography of spinal afferent termination as well as the olivo-cerebellar climbing fiber projection. This indicates that different olivary compartments are under different serotoninergic influence. The serotoninergic innervation of the dorsal accessory nucleus (DAO) of the inferior olive of the rat has been identified with electron microscopic radioautography after labelling with 3H-serotonin. The serotoninergic varicosities contain microcanaliculi, tubular-vesicular organelles and large granular vesicles. Few of the serotoninergic varicosities engage in typical synaptic junctions. However, non-junctional varicosities often display other ultrastructural indications of polarity and directed transmitted release. Electrophysiological results indicate that the harmaline-induced tremor, as well as the tremor component of the "serotonin-syndrome", depends on the serotoninergic innervation of the inferior olive. Thus, the sensitivity of different olivary compartments to the induction of rhythmic, synchronous activity by harmaline parallels the distribution of serotoninergic innervation. Neurotoxic destruction of the serotoninergic innervation leads to decreased sensitivity to harmaline. Further, the serotonin receptor agonist 5-methoxy-N,N-dimethyltryptamine, as well as monoamine oxidase inhibition + L-tryptophan loading, leads to rhythmic mass climbing fiber activity in the cerebellum and whole body tremor. A neuromodulatory effect of serotonin on the olivary action potential mechanisms is proposed.
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PMID:Morphological and functional studies on the serotoninergic innervation of the inferior olive. 616 26

Moclobemide (Ro 11-1163), a benzamide derivative, is a MAO-inhibitor which selectively and reversibly inhibits monoamine oxidase type A. Thirty-eight patients with episodic, chronic and atypical depressive disorder (DSM-III) were equally randomized to 6 weeks' treatment with either three daily doses of 100 mg moclobemide or 50 mg clomipramine. Both treatment groups improved with time as assessed weekly by the Hamilton Depression Scale and the Clinician's Overall Assessment of Depression State, and there was no interaction between treatment and time. Anticholinergic complaints, tremor and dizziness occurred more frequently on clomipramine, and they were longer lasting and more severe. Because of its low toxicity, good tolerance, its selectivity and reversibility moclobemide may be a better alternative than the older monoamine oxidase inhibitors.
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PMID:Moclobemide and clomipramine in the treatment of depression. A randomized clinical trial. 638 47

Chronic administration of amphetamine to cats (twice daily, in doses increasing from 5 to 15 mg/kg over a 10-day period) elicited a number of behaviors e.g., limb flicking, abortive grooming, and excessive head shaking, which were originally proposed as an animal behavioral model for studying the actions of hallucinogens that depress central serotonergic neurotransmission. This drug treatment produced large decreases (approximately 50%) in central nervous system serotonin (5HT) and its major metabolite, 5-hydroxyindoleacetic acid, and even larger decreases (approximately 90%) in the levels of dopamine (DA) and norepinephrine. Administration of the 5HT precursors L-tryptophan (25 mg/kg i.p.) or L-5-hydroxytryptophan (12.5 mg/kg i.p.), a direct-acting 5HT agonist (quipazine, 1 mg/kg i.p.) or a monoamine oxidase inhibitor (tranylcypromine, 4 mg/kg i.p.) produced no significant changes in these behaviors in cats treated chronically with amphetamine. Administration of a 5HT reuptake blocker (fluoxetine, 5 mg/kg i.p.) produced a small, but significant, decrease in the frequency of occurrence of these behaviors in amphetamine-treated cats. L-Dihydroxyphenylalanine (L-DOPA, 20 mg/kg i.p.) greatly potentiated these behaviors in cats chronically treated with amphetamine, but L-DOPA was totally ineffective in eliciting these behaviors in naive animals. The behavioral effects of apomorphine (2 mg/kg i.p.) were also significantly potentiated by chronic amphetamine pretreatment. The amino acid precursor of DA, L-tyrosine (25 mg/kg i.p.), and a DA reuptake blocker, bupropion (5 mg/kg i.p.) were without significant effect on these behaviors in amphetamine-treated cats. The data suggest that these cat behaviors are elicited by an action at central DA receptors and that these receptors become supersensitive following chronic amphetamine administration. Furthermore, there may be a qualitative change in DA receptors, since L-DOPA is very effective in potentiating these behaviors in cats treated chronically with amphetamine, but is totally ineffective in naive cats.
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PMID:Behavioral effects of serotonergic and dopaminergic drugs in cats following chronic amphetamine administration. 673 30

Serotonin mediated bulbospinal motor activities were examined in rats with experimental allergic encephalomyelitis (EAE)-induced-paraplegia. Treatment with monoamine oxidase inhibitors and L-tryptophan failed to elicit the components of the serotonin syndrome which involved levels of the neuraxis manifesting flaccid paralysis. Straub tail, hindlimb abduction and hindlimb rigidity did not occur. The motor responses represented at spinal segments just above the level of paraplegia, lateral head weaving and forepaw treading, were present but altered in the diseased rats. No impairment was evident in the production of head tremor or hyper-reactivity to accoustic and tactile stimuli. Similarly, in urethane-anesthetized EAE rats, serotonergically-evoked automatic swallowing activity was unchanged as judged by the effects of serotonin receptor agonists, and a serotonin precursor, a reuptake blocker and an antagonist. Our data support the conclusion that EAE-induced impairment of serotonergic neurotransmission is correlated with motor deficits manfested during the acute paralytic stage of the disease.
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PMID:Central serotonin receptor sensitivity in rats with experimental allergic encephalomyelitis. 696 16

Harmine, a hallucinogen with potent monoamine oxidase inhibitory properties, induced abnormal behavior, including tremor, scratching, head twitch and cage biting, in the mouse. A dose-dependent tremor was produced by all routes of administration of harmine. Although oxotremorine tremor was markedly suppressed by atropine, harmine tremor was unaffected by cholinergic drugs, remarkably inhibited by dopaminergic drugs, antidepressants and diazepam, mildly diminished by p-chlorophenylalanine, markedly augmented by 5-hydroxytryptophan and mildly increased by alpha-methyl-p-tyrosine. These findings suggest that a catecholaminergic (particularly dopaminergic) and serotonergic system imbalance plays an important role in the manifestation of harmine tremor. In view of these characteristics, harmine tremor may be useful as an effective experimental model for the evaluation of antiparkinsonism drugs, along with oxotremorine tremor because of the different mechanism of occurrence. In addition, harmine tremor appears to be useful in characterizing the properties of antidepressant drugs.
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PMID:Pharmacological characteristics of abnormal behavior induced by harmine with special reference to tremor in mice. 697 66

The hydrochloride salt of 2,3,3a,4,5,6-hexahydro-8-methyl-1H-pyrazino[3,2,1-j,k]carbazol hydrochloride (pirlindole) exerts pharmacological effects typical of antidepressants. This compound antagonizes the depressant effects of reserpine and tetrabenazine and potentiates the central effects of amphetamine and l-dopa. It also enhances the head-twitch effect of 5-hydroxy-tryptophan, the effects of noradrenaline, adrenaline, serotonin, tyramine on blood pressure as well as the hypertensive and tremor activities of tryptamine. Pirlindole inhibits the neuronal uptake of noradrenaline and exerts reversible, short-lasting anti-MAO activity. It does not possess anti-cholinergic activity. Clinical trials have shown pirlindole to be effective as an antidepressive drug.
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PMID:Pharmacological properties of 2,3,3a,4,5,6-hexahydro-8-methyl-1H-pyrazino [3,2,1-j,k]carbazol hydrochloride (pirlindole), a new antidepressant. 719 96

Panic disorder is a chronic illness that affects at least 3 percent of the population. Panic disorder is associated with significant morbidity and an increased risk of suicide. Patients generally present with multiple somatic and psychologic complaints, including heart palpitations, chest pain, tremor, shortness of breath, choking, nausea or abdominal distress, dizziness, derealization, fear of losing control or going crazy, fear of dying, paresthesias, chills or hot flushes, headache, diarrhea, insomnia, chronic fatigue, anxiety and depression. To make the correct diagnosis, these symptoms must be evaluated carefully since they also occur with serious cardiovascular, pulmonary, endocrinologic and neurologic disorders. Many effective treatments are available, including tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, benzodiazepines such as alprazolam and clonazepam, and psychotherapy.
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PMID:Panic disorder. 748 99

Application of the common marmoset to pharmacological studies was reviewed, especially employment of the animal as a model of Parkinson's disease were presented. The common marmoset is one of the New World monkeys with a body weight of 300-350 g. It is small enough to be easily handled and to be kept as a group in a room. In the fields of pharmacology, it has been used in studies of plasma renin activity inhibitors, lipoprotein, memory/learning, obstetrics, transplantation, toxicology, anxiolytic agents and virology/immunology. We showed that the common marmoset was a useful animal for studies on Parkinson's disease, dopamine metabolism by microdialysis and nausea/vomiting. The common marmoset was sensitive to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and developed permanent parkinsonism after MPTP injection. MPTP-treated common marmosets showed tremor and akinesia, and it remarkably responded to antiparkinsonian agents. A dopamine D1 agonist, which caused stereotyped behavior in rats, did not reverse parkinsonism in humans. We showed this agent did not have any antiparkinsonian effects on MPTP-treated common marmosets. MAO has subtypes, A and B, that have differences of distribution in different species. MAO type B inhibitors were applied for the treatment of Parkinson's disease. MAO subtype B inhibitors do not cause any change in behavior or extracellular concentration of dopamine or its metabolites in rodents. In MPTP-treated common marmosets, however, administration of a MAO type B inhibitor increased the antiparkinsonian effects of levodopa and decreased dopamine metabolites. The common marmoset is a suitable animal for the study of MAO type B inhibitors.
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PMID:[Application of the common marmoset to pharmacological studies]. 759 May 19

Parkinson's disease is a progressive neurodegenerative condition of unknown cause and with no known cure. The diagnosis is based on clinical findings of rest tremor, muscle rigidity, bradykinesia, and gait instability. Over 40% of patients develop a dementia syndrome that is largely distinct from Alzheimer's disease. Depression is common, also occurring in more than 40% of patients with PD. Careful evaluation in necessary to help distinguish Parkinson's disease from secondary causes of parkinsonism. Carbidopa/levodopa, dopamine agonists, and monoamine oxidase type B inhibitors are the mainstays of treatment. Anticholinergics and other agents may also be useful. Pharmacologic treatment must be carefully titrated to control symptoms and to avoid side effects. In advanced disease, dose-related dyskinesias, end-of-dose wearing-off effect, and unpredictable sudden motor fluctuations become very disabling and difficult to manage.
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PMID:Parkinson's disease: making the diagnosis, selecting drug therapies. 792 45

Straight and branched chain aliphatic monoamines, which are not normal tissue constituents, are deaminated selectively by type B monoamine oxidase (MAO-B). They exhibit a high affinity towards the active site of MAO-B and this made them very useful pharmacologically. An anticonvulsant prodrug, Milacemide [2-(N-pentyl)glycinamide] is deaminated by MAO-B and this facilitates a mechanism of delivering glycine into the CNS. We have found that 2-propyl-pentylamine (2-propyl-1-aminopentane) and N-(2-propylpentyl)glycinamide are also converted by MAO-B to valproic acid and glycine both in vitro and in vivo; these compounds, however, cause severe tremor. By attaching a propargylamine group the resultant series of aliphatic propargylamine derivatives have been shown to be very potent selective MAO-B inhibitors. They are chemically quite different from most other MAO-B inhibitors, since they do not possess any aromatic structures. The relatively short chain aliphatic propargylamines, i.e. N-2-pentyl-N-methylpropargylamine and N-2-hexyl-N-methylpropargylamine, are 4 to 5 times more potent and more selective than selegiline (1-deprenyl) with respect to the inhibition of MAO-B in brain following oral administration. Semicarbazide-sensitive amine oxidase (SSAO) catalyzes the deamination of not only longer chain aliphatic amines but also short chain aliphatic amines including methylamine. Formaldehyde is produced from methylamine by SSAO. Increased methylamine deamination may cause cellular damage in some pathological conditions, such as uraemia and diabetes. We have observed that cultured human endothelial cells are damaged by methylamine in the presence of SSAO. Inhibition of the SSAO activity completely protects these cells from the methylamine-SSAO induced damage.
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PMID:Deamination of aliphatic amines by type B monoamine oxidase and semicarbazide-sensitive amine oxidase; pharmacological implications. 793 Dec 56


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