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  • (−)-3PPP  (1)
  • Key words Tardive dyskinesia  (1)
  • 1
    ISSN: 1432-2072
    Keywords: Key words Tardive dyskinesia ; Mixture analysis ; Chronic haloperidol ; Rats ; Vacuous chewing movements
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Spontaneous adventitious oral movements which are produced in rats by very chronic (6- month) neuroleptic treatment have some phenomenologic and pharmacologic characteristics in common with tardive dyskinesia in humans. However, since not all of the features match, this putative model has been questioned and further support is warranted. Data from several laboratories support dichotomizing these neuroleptic-induced rat oral movements into “low”or “not TD-like” movements and “high”or “TD-like” movements, similar to the division of neuroleptic-induced involuntary movements in humans. Here, we have used mixture analysis to test this proposal statistically in 185 haloperidol-treated and 127 water-treated animals. Rats from several different studies were grouped together to form these two cohorts. The haloperidol dose, route of administration, rating technique, and balanced experimental groups were held constant across all experiments. Results show that two distinct groups of rat movements are induced by very chronic haloperidol treatment (1.5 mg/kg per day). The “low” vacuous chewing movement (VCM) group of rats had an average of 3.6 VCMs/5 min, and the “high” VCM group had an average of 16.1 VCMs/5 min; the conrol group, with a median VCM rate of 2.0 VCMs/5 min, demonstrated a single distribution. These data suggest that rats, like humans, dichotomize into two groups either expressing or not expressing “high” VCM dyskinesias with very chronic haloperidol treatment.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 88 (1992), S. 165-175 
    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
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