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)

Parkinson's disease no longer seems to be a disease entity caused by only one pathogenetic factor. The facile characterization of Parkinson's disease as a more or less isolated disorder of the dopaminergic system proves to be an unacceptable oversimplification of the pathology of the disease. Characteristically, not all dopaminergic systems of the central nervous system are involved in the degenerative process. In addition to the nigrostriatal dopaminergic pathway, parts of the glutamatergic, cholinergic, tryptaminergic, noradrenergic, adrenergic, serotonergic, and peptidergic neurons show serious cytoskeletal damage. In the light of these findings, drugs influencing these transmitter systems should be useful in the treatment of parkinsonian symptoms. For this reason, non-dopaminergic drugs are gaining more and more importance. Besides the theoretically interesting adenosine A2 receptor antagonists, budipine, a polyvalent potent new antiparkinsonian drug, has been tested in clinical studies. Budipine is a potent non-dopaminergic antiparkinsonian drug with pharmacological effects that are not comparable to those of conventional drugs applied in Parkinsonian pharmacotherapy. Budipine experimentally increased the brain content of noradrenaline, dopamine, serotonin, and histamine. The dopamine, serotonin, noradrenaline, gamma aminobutyric acid (GABA), and endorphine receptor affinities were not altered, but N-methyl-D-aspartate (NMDA) and sigma receptor affinities were increased as shown by in vivo and in vitro trials with budipine. MPTP (N-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine) and MPP+ antagonistic effects have also been demonstrated. Budipine also shows neuroprotective as well as symptomatic antiparkinsonian effects. In two randomized, double-blind, multicenter, placebo-controlled studies, relevant therapeutic effects have been observed in previously untreated, so-called "de-novo" parkinsonian patients and in subjects in later stages of the disease. Budipine significantly reduces akinesia, rigidity, and tremor. Optimal effects of budipine can be seen 4-6 weeks after starting treatment with this substance. Budipine can be added to all available antiparkinsonian drugs. An open, prospective, long-term study of 2532 patients with Parkinson's disease (Study BY701/01A) confirmed the favorable safety and tolerability profiles of budipine.
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PMID:Non-dopaminergic therapy in Parkinson's disease. 1099 61

Lesch-Nyhan syndrome (LNS) is a rare X-recessive disorder that leads to virtually complete deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Partial HPRT deficiency results in uric acid overproduction with subsequent hyperuricemia, nephrolithiasis, renal failure and gouty arthritis. In contrast, at complete HPRT deficiency, besides overproduction of uric acid neurological problems appear including spasticity, choreoathetosis, mental retardation, and compulsive self-mutilation. The cause for the uric acid overproduction has been clarified, but the connection between the enzyme deficiency and the neurological manifestations in LNS remains unclear. A hypothesis, which explains this relation, is proposed in the paper. The hypothesis has several important points most substantial of which is the accelerated biosynthesis of semiessential amino acid histidine that against the background of accelerated purine de novo biosynthesis results in 5-aminoimidazole-4-carboxamideribotide (AICAR) and histamine accumulation. The histamine and AICAR were determined to be the compounds that cause the neurobehavioral symptoms of LNS for several reasons. First, in the basal ganglia a balance between the direct (activating) and the indirect (inhibiting) pathways arising on the basis of the antagonistic and reciprocal dopamine-adenosine interactions normally exists. This balance can tonically regulate smooth voluntary movements and the activity of the thalamus, which, in turn, processes the afferent sensorimotor signals from the whole body to the all areas of the cerebral cortex and is concerned to modulate mental development and bring sensory information into awareness. Second, histamine is known to induce a selective damage in dopaminergic neurons inhibiting the direct dopaminergic pathway, which could lead to muscular rigidity, and slowness in initiating movements as well as tremor that are characteristic of Parkinsonism in LNS. Third, AICAribosid (AICAR breakdown product) is a potent adenosine A2a receptor antagonist inhibiting the indirect dopamine-adenosinergic pathway and, therefore, could be responsible for the choreoathetosis, dystonia and ballismus found in LNS. The excitatory-inhibitory disbalance in the basal ganglia could result in inadequate modification of the thalamus activity with subsequent mental retardation and symptoms that include the patients not being aware for their own bodies that could give rise to self-mutilation. Finally, a possibility for the creation of a new animal model that could exactly match the human LNS is proposed in the paper.
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PMID:The biochemical basis of the neurobehavioral abnormalities in the Lesch-Nyhan syndrome: a hypothesis. 1519 65