Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of IVT serotonin [5-hydroxytryptamine (5-HT)] and dopamine (DA) administration have been studied in rats and marmosets (Callithrix jacchus). In rats, 5-HT (114 and 170 micrograms/10 microliters) produced the same behavioral effects observed after IP administration of its precursors and agonists. The same doses of 5-HT used for rats produced only part of the behavioral effects in marmosets after IP administration of 5-HT precursors and agonists. Ataxia, vomiting, and decreased motor activity were observed, but not drowsiness or teeth-chattering. However, IVT administration of DA (400 micrograms/10 microliters dose) produced head movements or checking, ataxia, tongue out, and decreased motor activity. These findings differ from those observed after IP administration of l-DOPA and DA agonists, which increase motor activity.
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PMID:Behavioral effects of the intraventricular administration of 5-HT and dopamine in the common marmoset (Callithrix jacchus). 825 14

The levels of monoamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA) were measured in lumbar cerebrospinal fluid (CSF) from 10 patients with late onset ataxia, 8 patients with alcoholic ataxia and 18 control patients. The levels did not differ significantly among the three groups of patients suggesting that the central neuronal systems utilizing dopamine, noradrenaline and 5-hydroxytryptamine do not have a significant pathophysiological role in these forms of ataxias. The measurement of CSF amine metabolites probably does not contribute to the differential diagnosis of ataxias.
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PMID:Biogenic amine metabolites in the CSF of patients with late onset and alcoholic ataxias. 850 61

Panic disorder, a psychiatric disorder characterised by frequent panic attacks, is the most common anxiety disorder, affecting 2 to 6% of the general population. No one line of treatment has been found to be superior, making a risk-benefit assessment of the treatments available useful for treating patients. Choice of treatment depends on a number of issues, including the adverse effect profile, efficacy and the presence of concomitant syndromes. Tricyclic antidepressants (TCAs) are beneficial in the treatment of panic disorder. They have a proven efficacy, are affordable and are conveniently administered. Adverse effects, including jitteriness syndrome, bodyweight gain, anticholinergic effects and orthostatic hypotension are commonly associated with TCAs, but can be managed successfully. Selective serotonin (5-hydroxytryptamine; 5HT) reuptake inhibitors are also potential first line agents and are well tolerated and effective, with a favourable adverse effects profile. There is little risk in overdose or of anticholinergic effects. Adverse effects include sedation, dyspepsia and headache early in treatment, and sexual dysfunction and increased anxiety, but these can be effectively managed with proper dosage escalation and management. Benzodiazepines are an effective treatment, providing short-term relief of panic-related symptoms. Patients respond to treatment quickly, providing rapid relief of symptoms. Adverse effects include ataxia and drowsiness, and cognitive and psycho-motor impairment. There are reservations over their first-line use because of concerns regarding abuse and dependence. Monoamine oxidase inhibitors, because of their adverse effects profile, potential drug interactions, dietary restrictions, gradual onset of effect and overdose risk, are not considered to be first-line agents. They are effective however, and should be considered for patients with refractory disease. Valproic acid (valproate sodium), while not intensively studied, shows potential for use in panic disorder. More studies are needed in this area before the available data can be confirmed. As a supplement to drug therapy, cognitive behavioural therapy is effective. It is well tolerated, and may be beneficial in certain clinical situations. Its main drawback is the time commitment and effort needed to be made by the patient.
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PMID:A risk-benefit assessment of pharmacological treatments for panic disorder. 963 87

We examined the involvement of multiple monoaminergic receptors in the induction of spontaneous tail-flicks (STFs) by the open channel blocker at N-methyl-D-aspartate (NMDA) receptors, dizocilpine, and the NMDA recognition site antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP). At doses eliciting a maximal STF response, dizocilpine and CPP elevated levels of norepinephrine, but not dopamine or serotonin, in dialysates of nucleus accumbens, their known locus of action in eliciting STFs. Chemically diverse alpha(2)-adrenergic receptor (AR) antagonists atipamezole, L745,743, RX821,002, idazoxan, and desfluparoxan abolished induction of STFs by dizocilpine, whereas the preferential alpha(1)-AR antagonists prazosin, WB4101, and ARC239 were weakly active: relative potencies in blocking STFs correlated significantly with affinity at alpha(2)-ARs. The D(1)/D(5) receptor antagonists SCH23390, SCH39166, and NNC756 potently abolished STFs, whereas the D(2) antagonist L741,626, the D(3) antagonists GR218,231 and S14297, and the D(4) antagonists S18126 and L745,870 were inactive. D(1) and alpha(2)-AR antagonists also blocked induction of STFs by CPP. Blockade of dizocilpine-induced STFs was specific inasmuch as idazoxan and SCH 23390 did not modify induction of ataxia by dizocilpine. Antagonists at multiple 5-hydroxytryptamine receptors failed to modify induction of STFs. Finally, dizocilpine-induced STFs were blocked by clozapine and 11 other antipsychotics, the potency of which correlated significantly with affinity at alpha(2)-ARs. In conclusion, STFs evoked by interruption of transmission at NMDA receptors are dependent on D(1) receptors and alpha(2)-ARs for their expression. Antagonism of the alpha(2)-ARs is involved in their blockade by antipsychotics. This model should facilitate exploration of interrelationships between glutamatergic and monoaminergic mechanisms involved in psychiatric and neurologic disorders.
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PMID:Induction of spontaneous tail-flicks in rats by blockade of transmission at N-methyl-D-aspartate receptors: roles of multiple monoaminergic receptors in relation to the actions of antipsychotic agents. 1064 Mar 5

Injury to the cerebellum commonly results in clumsiness or uncoordinated movement, which is referred to as ataxia. The severity of ataxia varies according to the extent of the lesion. Severe ataxia usually restricts activities of daily living, impairs mobility, and increases level of disability. Recent studies investigating use of serotonin agonists in the treatment of ataxia have produced mixed results; however, buspirone with an affinity specific to the 5-hydroxytryptamine(1A) subreceptors has shown promise. In this brief report, we use a prospective, open, single-case experimental design to describe substantial subjective and objective dose-dependent improvement of ataxia after unusually high doses of buspirone taken by a patient whose severe ataxia was due to lithium toxicity.
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PMID:Ataxia from lithium toxicity successfully treated with high-dose buspirone: a single-case experimental design. 1149 97

The antiemetic and emetic actions of the anticancer drug cyclophosphamide injected intracerebroventricularly (i.c.v.) and intravenously (i.v.) through chronically implanted cannulae were investigated in unanaesthetized cats. Cyclophosphamide in single doses was injected into the cerebral ventricles and intravenously for 5 consecutive days. The antiemetic effect was regularly obtained, whereas the emetic effect was unpredictable and of low incidence. The antiemetic effect of i.c.v. and i.v. cyclophosphamide was assessed, when the neurotoxic (mydriasis, restlessness, emesis, ataxia, muscular weakness) signs subsided, against i.c.v. noradrenaline- and clonidine-induced emesis. Noradrenaline-induced emesis was dose-dependently and dose-independently inhibited with i.c.v. and i.v. cyclophosphamide. On the other hand, i.c.v. cyclophosphamide inhibited the clonidine-induced emesis in dose-independent manner, while i.v. injection of the anticancer drug had no significant effect on the emesis. The inhibition of emesis was consistently obtained and no significant differences in the antiemetic potency were found between 1 and 5 consecutive days of treatment with cyclophosphamide. However, the inhibition of noradrenaline-induced emesis was dose-dependent only after first administration of i.c.v. cyclophosphamide. It is assumed that noradrenaline acts at alpha-adrenoceptors within the area postrema and clonidine at alpha-adrenoceptors within and outside the area postrema as well as at muscarinic cholinoceptors, 5-hydroxytryptamine, dopamine and histamine H1 and H2 receptors, outside the area postrema, of multitransmitter system subserving the central regulation of emesis. It is suggested, therefore, that the antiemetic effect of cyclophosphamide at the receptors of the multitransmitter central emetic system is non-specific. In general, the antiemetic effect, even non-specific, of an anticancer drug could have practical implication. Namely, when a combination of two or more anticancer drugs are used for chemotherapy, the emesis could not occur if one of them could antagonize the emesis induced by other anticancer drug/s. Finally, cyclophosphamide injected i.c.v., but not i.v., evoked shortlasting emesis in about 20% of cats. Since the emesis was unpredictable and of low incidence it was not possible to study the mechanism/s and site/s of action of the anticancer drug.
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PMID:Emesis: antiemetic effect of cyclophosphamide at central receptors of multitransmitter system in the cat. 1241 47

An 85-year-old woman developed sudden confusion and dysarthria progressing to mutism, orobuccal dyskinesias, generalized tremors worse with activity, ataxia, and rigidity with cog wheeling without high-grade fevers or dysautonomia. These findings were related temporally to the institution of mirtazapine as monotherapy for a major depressive illness with superimposed anxiety disorder. Withdrawal of the agent resulted in early notable clinical resolution with only residual hypertonia after 2 weeks. This is a rare report of serotonin syndrome induced by mirtazapine monotherapy. The hypothesized pathophysiologic mechanism in this case is overstimulation of serotonin (5-hydroxytryptamine or 5-HT) type 1A receptors (5-HT(1A)) in the brainstem and spinal cord in an individual with risk factors for hyperserotoninemia resulting from reduced, acquired endogenous serotonin metabolism.
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PMID:Mirtazapine-induced serotonin syndrome. 1464 4

Cerebellar syndrome is one of the most disabling developments in multiple sclerosis (MS). In neurodegenerative disorders, cerebellar syndrome is thought to be related to a neurochemical deficit of 5-hydroxytryptamine (5-HT). Previous studies found that a levorotatory form of 5-hydroxytryptophan, a 5-HT precursor, and ondansetron, a 5-HT(3) receptor antagonist, decreased cerebellar symptoms in Friedreich's ataxia and MS. We studied the effect of another 5-HT(3) receptor antagonist, dolasetron mesilate, on cerebellar syndrome in MS patients.Thirty-four MS patients were included in a placebo-controlled double-blind crossover study. They received a single dose of intravenous dolasetron mesilate or placebo. A quantitative evaluation of cerebellar syndrome using the nine-hole peg test and an ataxia score comprising static and kinetic parameters were performed before and after each treatment. No statistical difference was observed in the dolasetron mesilate group, compared with the placebo group. There was, however, inter-individual variability in the treatment response. This double-blind study on cerebellar syndrome in MS patients did not confirm the positive effect of dolasetron mesilate suggested by previous studies.
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PMID:Double-blind crossover study with dolasetron mesilate, a 5-HT3 receptor antagonist in cerebellar syndrome secondary to multiple sclerosis. 1458

Neonatal cocaine is known to affect the developing serotonergic system in many brain structures, including the cerebellum. Changes in the cerebellar Purkinje cells after drug exposure are well documented and result in impairment of movement and other cerebellar disorders such as ataxia. These cells have a major postnatal developmental pattern; therefore, neonatal exposure to cocaine is likely to affect them. In this work, male and female Wistar rats were injected with 15 mg of cocaine hydrochloride/kg body weight/day, subcutaneously, in two daily doses, from postnatal day 1 (PND1) to PND29. Controls were given 0.9% of saline. On PND14, PND21, and PND30, rats were transcardially perfused, and brains removed and cryoprotected. Coronal sections from the cerebellum were processed for immunocytochemistry of cells containing serotonin (5-hydroxytryptamine, or 5-HT). At the same postnatal age, rats from at least three different litters were sacrificed by decapitation, and brains were dissected for determination of 5-HT in the cerebellum by high-performance liquid chromatography with electrochemical detection. Upon the expected distribution of immunoreactivity to 5-HT, an abnormal immunoreactivity to 5-HT was observed in the Purkinje cells of six cocaine-exposed animals, but not in control animals. Also, levels of cerebellar 5-HT in cocaine-exposed rats were significantly increased on PND21. These results, together with previously reported observations of altered patterns of motor behavior, indicate that neonatal cocaine exposure affects the serotonergic cerebellar system, altering the standard development of Purkinje cells and possibly compromising the motor function.
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PMID:Abnormal immunoreactivity to serotonin in cerebellar Purkinje cells after neonatal cocaine exposure. 1554 72


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