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)

We found that 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine dihydrochloride (SA4503), a potent and selective sigma 1 receptor agonist, significantly enhanced the cerebral acetylcholine (ACh) release in the rat using in vivo brain microdialysis technique. Interestingly, the significant enhancement of ACh release elicited by SA4503 was observed in the rat frontal cortex and hippocampus, although the striatal ACh release was unchanged. This cortical ACh release was fully reversed by haloperidol, a prototype sigma receptor antagonist, or by N, N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride, a putative sigma 1 receptor antagonist. In addition, this enhanced ACh release by SA4503 was inhibited by tetrodotoxin, a Na+ channel blocker. However, tetrahydroaminoacridine, an acetylcholinesterase inhibitor, significantly increased the extracellular ACh level in the rat frontal cortex and weakly increased the hippocampal level. This compound also showed the significant increase of extracellular ACh level in the rat striatum. Moreover, tetrahydroaminoacridine markedly produced cholinomimetic side-effects, such as hypothermia, tremor, miosis and lacrimation. However, SA4503 did not produce these cholinomimetic side-effects. These findings suggest that SA4503 enhances the ACh release that is mediated through a novel mechanism, namely sigma 1 receptor subtype. Furthermore, SA4503 has regional differences in the enhancement of cerebral ACh release, and did not produce cholinomimetic side-effects. These profiles are different from tetrahydroaminoacridine.
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PMID:Enhancement of acetylcholine release by SA4503, a novel sigma 1 receptor agonist, in the rat brain. 885 82

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