Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We propose a serotonergic hypothesis for cerebellar ataxia. The levorotatory form of 5 hydroxytryptophan has been shown to be partially active in subtypes of cerebellar ataxia, including cerebellar cortical atrophy (CCA). Buspirone, a 5-HT1A agonist usable in human medicine, has been studied in a group of 14 patients with cerebellar cortical atrophy. Patients were given Buspirone for 2 months. The evaluation of cerebellar ataxia was made by a semi-quantitative scale, 10 fully quantitative measures and measurements of the sway path and sway area of the center of gravity at posturography. The primary endpoints were the modifications of the ataxia scores. At 2 months, the decrease of the ataxia scores was significant, both in the intention-to-treat (14 cases) and target (11 cases) populations. In the target population, secondary endpoints like the time measurements for pronouncing a standard sentence, the time for drawing a ladder and posturographic parameters were significantly improved; the mean global ataxia score was improved by 37.4%. These preliminary data might confirm a link between cerebellar ataxia and the metabolism of serotonin.
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PMID:[Effect of buspirone, a serotonergic 5-HT-1A agonist in cerebellar ataxia: a pilot study. Preliminary communication]. 878 1

We have previously proposed a serotonergic hypothesis for cerebellar ataxia and mentioned that the levorotatory form of 5-hydroxytryptophan, a serotonin precursor, is partially active in subtypes of cerebellar ataxia, including cerebellar cortical atrophy (CCA). It has been demonstrated that 5-HT1A serotonergic receptors play an important role in the control of Purkinje cells discharges and in the inhibition of the release of glutamate by cerebellar glutamatergic terminals. To test further the serotonergic hypothesis of cerebellar ataxia, we administered buspirone, a 5-HT1A agonist usable in human medicine, in a randomized double blind drug placebo trial for 4 months. Nineteen patients with CCA were included; nine patients were given placebo and 10 Buspirone, at the mean dose of 0.69 mg/kg. The evaluation of ataxia was based on a static and a kinetic ataxia scale, fully quantitative measures and the evaluation of the sway path and area at posturography. At 4 months, a significant effect of buspirone was observed for drug induced gains of the kinetic score, two items of the static score, and the maximum duration of standing upright with feet together. These results indicate that a novel chemical therapeutic approach is possible for cerebellar ataxia; moreover, they support the existence of a link between cerebellar ataxia and disturbances of the serotonergic cerebellar system, especially a serotonergic deficit.
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PMID:Buspirone, a serotonergic 5-HT1A agonist, is active in cerebellar ataxia. A new fact in favor of the serotonergic theory of ataxia. 919 69

Tandospirone citrate (tandospirone) is an anti-anxiety drug that acts by combining with serotonin receptor (5-hydroxytryptamine-1 A [5-HT1A]). Recently, there have been a few reports of its potential role in the treatment of cerebellar ataxia. We report the first case of a patient with Machado-Joseph disease in which we successfully treated cerebellar ataxia. In addition, his leg pain, insomnia, anorexia, and depression, which are thought to be related to 5-HT1A receptors, were also remarkably alleviated by treatment with tandospirone.
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PMID:Beneficial effects of tandospirone on ataxia of a patient with Machado-Joseph disease. 1195 22

The confirmed pharmacological treatment of cerebellar ataxia is still lacking. In a recent preliminary trial, we showed that D-cycloserine, a partial NMDA allosteric agonist, may relieve the symptoms. In this paper, major clinical trials to relieve ataxic symptoms are reviewed. Previous studies showed some efficacy of physostigmine in ataxic patients. However, physostigmine did not improve the ataxia in a recent double-blind crossover study. The replacement therapy of the deficient cholinergic system with choline or choline derivatives was tried in patients with Friedreich's ataxia and other ataxic patients, but the result was not definitive. A levorotatory form of hydroxytryptophan (a serotonin precursor), a serotoninergic 5-HT1A agonist, a serotoninergic 5-HT3 antagonist, and a serotonin reuptake inhibitor were also used for the therapy for ataxia. In a double-blind randomized study, buspirone, a 5-HT1A agonist was active in cerebellar ataxia, but the effect is partial and not major. The effects of the studies with the other serotoninergic drugs were not consistent. The effect of sulfamethoxazole-trimethoprim therapy in spinocerebellar ataxia type3/Machado-Joseph disease (MJD) was reported, although the therapy improved spasticity or rigidity, rather than ataxia. In contrast to previous studies, sulfamethoxazole-trimethoprim therapy in MJD had no effect in a 2001 double-blind crossover study. The thyrotropin-releasing hormone, D-cycloserine, and acetazolamide for SCA6 may have some efficacy. However, a well-designed double-blind crossover trial is needed to confirm the effect.
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PMID:Pharmacological treatments of cerebellar ataxia. 1523 78

Effective, pharmacologic approaches to the treatment of cerebellar ataxia are lacking or inadequate. We recently reported preliminary evidence that tandospirone citrate (tandospirone), a 5-HT1A agonist, improved cerebellar ataxia in patients with Machado-Joseph disease (MJD). In the course of that study, we found that such treatment also alleviated the pain associated with cold sensations in the legs, insomnia, anorexia, and depression, all of which are thought to be mediated through activation of the 5-HT1A receptor. In this paper, we reviewed the few published clinical trials that involved the use of 5-HT1A receptor agonists for the treatment of cerebellar ataxia, and discussed the current theories regarding their mechanism of action. Cortical cerebellar atrophy (CCA) was reported, in a double-blind study, to be amenable to treatment with tandospirone. Other types of spinocerebellar degeneration (SCD) i.e., olivopontocerebellar atrophy (OPCA) and Machado-Joseph disease (MJD) have also been reported to respond to the drug, but these have been small studies. Responsive patients exhibited only mild ataxia. The doses of 5-HT1A agonists that have been used successfully ranged from 12.5 mg/day to 60 mg/day (or 1 mg/kg), and were well tolerated by most patients.
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PMID:Treatment of cerebellar ataxia with 5-HT1A agonist. 1614 54