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)

An experimental and clinico-pharmacological study of sodium valproate, a GABA-ergic drug, was conducted to elucidate the role of gamma-aminobutyric acid in the mechanisms responsible for affective disturbances, in particular for anxiety. A tranquilizing effect of the drug, comparable with the action of diazepam, was established in a conflict situation model in experimental animals. Using clinico-psychological methods the authors showed a distinct tranquilizing action of valproate in patients suffering from neurotic and neurosis-like disorders with manifestations of anxiety in the structure of the psychopathological syndrome. It was established that this action was accompanied by no manifestations of myorelexation, ataxia or somnolence characteristic of tranquilizers of the benzodiazepine series. The presence of tranquilizing properties in the GABA-ergic drug sodium valproate confirms the suggestion that a certain relationship exists between the GABA system and anxiety.
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PMID:[Anxiolytic action of sodium valproate (possible role of gamma-aminobutyric acid in affective disorders)]. 286 Jul 64

Nabilone is a new orally active cannabinoid for the treatment of severe gastrointestinal toxicity associated with cancer chemotherapy. The pharmacological profile of nabilone suggests that it acts primarily by preventing emesis controlled by the medulla oblongata, although its secondary mild anxiolytic activity may contribute to the overall efficacy. Nabilone 2mg twice daily starting 12 hours prior to, and continued for the duration of, chemotherapy produces significant reduction in the severity and duration of nausea and the frequency of vomiting in about 50 to 70% of patients with severe symptoms refractory to conventional therapy. Nabilone has proven to be more effective in controlling symptoms and preferred by more patients than prochlorperazine 10mg 2 to 4 times daily in a limited number of studies, despite a higher incidence of side effects. Comparative trials against other new antiemetic agents, such as high dose metoclopramide, and use of nabilone in combination with other antiemetics remain to be undertaken. The incidence of side effects is high with nabilone; drowsiness, dizziness and/or vertigo occur in 60 to 70% of patients, but rarely lead to drug withdrawal, although more troublesome effects, such as postural hypotension, ataxia, vision disturbance and toxic psychoses, may cause discontinuation of therapy. Thus, nabilone offers an effective alternative to the treatment options available in a difficult therapeutic area - those patients with severe gastrointestinal side effects from cancer chemotherapy who are refractory to conventional therapy.
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PMID:Nabilone. A preliminary review of its pharmacological properties and therapeutic use. 286 27

7-Chloro-5-(2-fluorophenyl)-1,3-dihydro-1-(2,2,2-trifluoroethyl)-2H-1,4- benzodiazepine-2-thione (quazepam, Sch 16134, Dormalin) was evaluated for evidence of systemic toxicity, carcinogenicity and reproductive toxicity in several laboratory animal species including the hamster. Mutagenic potential was also assessed in one in vivo and three in vitro assays. In some studies, diazepam was used as a comparative control. Oral LD50 values were greater than 5000 mg/kg in the mouse and rat while i.p. LD50 values were approximately 900 and 2900 mg/kg in the mouse and rat, respectively. Studies in hamsters for 4 weeks at doses up to 500 mg/kg/d and for 51 weeks at doses up to 120 mg/kg/d demonstrated that the liver was the principal target organ in this species with the effects upon the liver related to dose and duration of dosing. Studies in the squirrel monkey for 13 and 52 weeks at doses up to 50 mg/kg/d demonstrated a transient ataxia, hypoactivity and somnolence during the initial two weeks of dosing. No unusual necropsy or microscopic observations were noted in the 13-week study. Male reproductive organs of quazepam-dosed monkeys were reduced in weight after 52 weeks. Moderate to marked impairment of spermatogenesis and higher liver weights with moderate to marked fatty change in both sexes were observed in groups given diazepam. Abrupt withdrawal of quazepam or diazepam after 52 weeks of dosing was associated at all dose levels with excitability, hyperactivity and convulsions. Two quazepam- and all diazepam-dosed monkeys died.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preclinical safety evaluation of the benzodiazepine quazepam. 289 Mar 57

The benzodiazepine clonazepam was approved for the treatment of epilepsy in 1976. To study its use in acute mania, the author compared clonazepam with lithium in a crossover trial. Clonazepam proved more effective than lithium in controlling the symptoms of mania and caused fewer manifestations of parkinsonism. Associated side effects included ataxia, drowsiness, and behavioral changes. No treatment-emergent depression was observed. Neither clonazepam nor any other benzodiazepine is recommended in schizoaffective or schizophrenic disorders because of the high risk of dependence in those patients, in contrast to manic-depressives. For the maintenance treatment of bipolar disorder, lithium is recommended as the initial agent, with L-tryptophan added if concomitant medication is needed. Clonazepam can then be added as the anticonvulsant, if necessary. In the treatment of acute mania, clonazepam is recommended for the first week of treatment, and lithium is added in the beginning of the second week, thus avoiding the use of neuroleptics.
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PMID:The use of benzodiazepines in the treatment of manic-depressive illness. 290 43

A post-mortem examined case of herpetic brainstem encephalitis is presented. Clinically, the patient had cephalalgia followed by ataxia, drowsiness and multiple palsies of some cranial nerves, developing into death in eight days. The pathologic examination of the brain showed necrotizing encephalitis in multiple foci limited to the brainstem, more distinctly in the pons and medulla oblongata. The technique of immunoperoxidase revealed rare glial cells with intranuclear immunoreactivity for herpes antigen. Rare viral particles with the morphological characteristics of the herpesvirus were identified in the nuclei of neurons in 10% formol fixed material. This is the second reported case of herpetic brainstem encephalitis confirmed by post-mortem examination. The pathway used by the virus to reach the central nervous system and its posterior dissemination to the oral cavity, the orbitofrontal region and the temporal lobes as well as to the brainstem, after a period of latency and reactivation, are discussed.
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PMID:[Herpetic brain stem encephalitis: report of an autopsied case with immunohistochemical and electron microscopy studies]. 303 59

We report three children with benign paroxysmal torticollis (BPT) and review the literature. BPT represents a self-limited disorder that occurs mainly in infancy and in females. The condition is characterized by recurrent spells of torticollis which may, or may not, be accompanied by other symptoms such as vomiting, pallor, ataxia, irritability and drowsiness. The diagnosis of BPT should be established clinically, although, in some cases, it is necessary to rule out conditions such as posterior fossa tumor, cervical dislocation, ocular palsy, dystonia due to side effects of drugs, or Sandifer's syndrome. The etiology of the syndrome remains unknown and, at present, there is no effective therapy.
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PMID:[Benign infantile paroxysmal torticollis. Apropos of 3 cases]. 305 50

Occurrence of encephalitozoonosis in farm breeding of blue fox is described. Fifty youngs of eight breeding females were infected, mortality was 88%. The main clinical symptoms of the disease were somnolence, ataxia, vision disorders, clonic spasms, at a protracted course also retarded growth. Typical nonpurulent microgranulomata with occurrence of individual spores and cysts of Encephalitozoon cuniculi were demonstrated in liver and central nervous system. Further, diffusion interstitial nephritis and necrotizing angiitis were determined. In breeding females, chronical interstitial nephritis was determined, without detection of the causative agent. A probable source of infection was the feeding of dead rabbits with subsequent transmission to progeny.
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PMID:[Encephalitozoonosis in farm-bred arctic blue foxes (Alopex lagopus)]. 308 63

The actions of the serotonin precursor 5-hydroxytryptophan (5-HTP), the agonist 5-methoxy-N,N-dimetyltryptamine (MeODMT) and quipazine (QPZ) and the antagonists cyproheptadine, methysergide and metergoline, were studied in the rat and in the common marmoset (Callithrix jacchus). The precursor and agonists elicited head shakes, forepaw padding, splayed hindlimbs, tremor and Straub tail in the rat. However, head shakes were not observed after MeODMT and Straub tail was not observed after QPZ. Carbidopa plus 5-HTP potentiated only head shakes, while tranylcypromine (TCP) plus 5-HTP potentiated all the behaviors above. In the marmoset, the action of these drugs elicited drowsiness, teeth chattering, ataxia, vomiting and decreased motor activity, although vomiting was not elicited by MeODMT and ataxia and drowsiness by QPZ. Although TCP plus 5-HTP potentiated all these behaviors, carbidopa plus 5-HTP was not effective. Rats treated with the antagonists (1.0, 5.0 and 10 mg/kg doses) did not show any of these behaviors, but marmosets treated with the same drugs developed "drowsiness", vomiting, and decreased motor activity; nonetheless, cyproheptadine (5.0 and 10 mg/kg doses) did not elicit "drowsiness", while increasing motor activity and the number of head shakes. Pretreatment of marmosets with these antagonists blocked only teeth chattering elicited by MeODMT (4.0 mg/kg) and QPZ (10 mg/kg). Pretreatment with haloperidol, p-chlorophenylalanine and alpha-methyl-P-tyrosine had no effect. The data obtained show that rats and marmosets present differential behavioral responses to the 5-HT drugs used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rats and marmosets respond differently to serotonin agonists and antagonists. 311 2

We report five episodes of carbamazepine (CBZ) intoxication in four patients. Clinically, there were four distinct stages: I--coma, seizures (CBZ levels more than 25 micrograms/ml [105 mumol/l]); II--combativeness, hallucinations, choreiform movements (15 to 25 micrograms/ml [65 to 105 mumol/l]); III--drowsiness, ataxia (11 to 15 micrograms/ml [45 to 65 mumol/l]); and IV--potentially catastrophic relapse (less than 11 micrograms/ml [45 mumol/l]). Pharmacokinetic studies revealed a prolongation of the CBZ half-life, elevation of the CBZ-epoxide/CBZ ratio, and emergence of CBZ-epoxide as a significant toxic metabolite. A treatment approach is proposed including repeated gastric lavage, detection of an insoluble tablet coagulum, electrolyte monitoring, avoidance of cathartics, and treatment of seizures with diazepam and phenytoin.
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PMID:Massive carbamazepine overdose: clinical and pharmacologic observations in five episodes. 336 74

The clinical features of refractory epilepsy were studied in comparison between 135 patients in a refractory group and 103 in a controlled group. All the children were Japanese. The clinical features of the refractory group were the onset of epilepsy during the first year of life, absence of family history, retarded development before the onset, phakomatoses, daily or weekly seizures, secondarily generalized epilepsy, and marked EEG abnormalities at the initial visit, a change of types in epilepsy, no improvement in EEG findings, mental deterioration or severe retardation during the follow-up. The number of drugs was increased and relatively new drugs such as carbamazepine, valproic acid or clonazepam were frequently administered. The side effects, including gum hypertrophy, drowsiness, hypertrichosis, ataxia or increased serum-GTP, were more frequent in the refractory group.
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PMID:Clinical features of intractable epilepsy in Japanese children. 344 34


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