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  • 1
    Electronic Resource
    Electronic Resource
    Drug-induced oral dyskinesias in rats after traditional and new neuroleptics (1995)
    Springer
    Journal of neural transmission 101 (1995), S. 41-49 
    Details
    ISSN: 1435-1463
    Keywords: Tardive dyskinesia ; antipsychotic medications ; atypical neuroleptics ; haloperidol ; clozapine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tardive dyskinesia (TD) is a serious human side effect of neuroleptic treatment in psychotic disorders. Although the etiology is clear (ie. chronic neuroleptic drugs), its pathophysiology has not yet been satisfactorily explained. This is important not only theoretically but also to inform drug development, allowing the introduction of antipsychotic compounds without TD liability. The development of an animal condition which putatively models these delayed onset dyskinesias, has provided a technique to differentiate between neuroleptic drug effect and dyskinesia correlates. We report here the development of oral dyskinesias in rats in response to a number of different neuroleptics, which have a range of neurochemical and clinical characteristics. Traditional neuroleptics (e.g. haloperidol) produced rat oral dyskinesias, in an open-cage environment. Clozapine, while it produced an increased rate of oral movements, showed a significantly decreased potency in this model. SCH23390 (D1 antagonist) neither produced the oral movements nor modified their onset by coadministration with raclopride. These data replicate and extend other similar studies in the literature. They suggest that clozapine differs from traditional neuroleptics with respect to motor side effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01271544
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacologic properties of (−)-3PPP (preclamol) in man (1992)
    Springer
    Journal of neural transmission 88 (1992), S. 165-175 
    Details
    ISSN: 1435-1463
    Keywords: Partial dopamine agonist ; schizophrenia ; (−)-3PPP ; antipsychotic ; autoreceptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The dopamine (DA) autoreceptor agonist (−)-3PPP (preclamol) was tested in male schizophrenic volunteers for safety. The drug was administered intramuscularly in a single rising dose design, crossed with a similar “rising dose” placebo period; all evaluations and raters were blind to drug or placebo administration. Pharmacokinetic, endocrine, safety, and mental status outcome measures were completed before and after each single dose of drug or placebo. Pharmacokinetic analysis showed blood levels between 200–500 pmoles/ml after the intramuscular drug doses of 30–40 mg. Drug half life is 2–2.5 hrs. Growth hormone (GH) levels were elevated in a linear fashion to the 30 mg dose; whereafter, the drug failed to affect GH at all. All safety evaluations were negative, including any untoward effects on the major organ systems. After single dose drug administration, evidence of antipsychotic action occurred in two of the four subjects. This study suggests that (−)-3PPP/preclamol is a safe drug for study in the treatment of schizophrenia and may have antipsychotic efficacy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01244730
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Tiagabine inhibits haloperidol-induced oral dyskinesias in rats (1994)
    Springer
    Journal of neural transmission 95 (1994), S. 63-69 
    Details
    ISSN: 1435-1463
    Keywords: Tardive dyskinesia ; haloperidol ; GABAmimetic ; tiagabine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Chronic administration of haloperidol to male Sprague Dawley rats for 6 months at a dosage of 1.5 mg/kg/day produces oral dyskinesias in a significant percent of the treated group. This has been used as an animal model of tardive dyskinesia in several laboratories, because the rat movements display characteristics reminiscent of the human dyskinetic condition. Previously, we have reported a reduction in these haloperidol-induced oral dyskinesias with the coadministration of a direct acting GABA agonist progabide. Here, we have tested an indirect acting GABA agonist, tiagabine, coadministered with haloperidol, for its effect on the oral dyskinesias. At a dosage of 75 mg/kg/day tiagabine significantly inhibited the onset of vacuous chewing movements (VCMs), decreasing the average movement severity from 11.2 ± 2.0 to 4.4 ± 1.4, compared with a placebo rate of 1.3 ± 0.5 (VCMs/5 min). These data support the proposition that an effective, potent GABAmimetic coadministered with haloperidol, will block the onset of rat oral dyskinesias. This conclusion has important implications for the treatment and prevention of tardive dyskinesia in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01283031
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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