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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 75 (1981), S. 240-244 
    ISSN: 1432-2072
    Keywords: Haloperidol ; Plasma concentration ; Antiemetic effect ; Dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A positive and highly significant correlation was found between SC dose, plasma concentration, and antiemetic effect of haloperidol in the dog. To protect dogs from apomorphine-induced emesis, a concentration of 1 ng haloperidol/ml plasma was always sufficient, whereas protection from emesis was never obtained with plasma levels lower than 0.53 ng/ml. The elimination rate of haloperidol from plasma varied from 1.53 to 2.60 among different animals. Thus, the interindividual variability to haloperidol was surprisingly low. Antiemetic effect and plasma elimination of haloperidol were not related to body weight.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Dog ; Self-stimulation ; Apomorphine ; Haloperidol ; Stimulus control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The interaction between various doses of apomorphine and haloperidol on intracranial self-stimulation in the dog was studied using a pradigm in which reinforcing brain-stimulation was controlled by a discriminative auditory stimulus. Reinforced leverpressing was decreased by low doses of apomorphine and completely suppressed by stereotypogenic doses. At various doses of apomorphine, low doses of haloperidol either increased response inhibition by enhancing stereotypy, or increased lever pressing by reducing stereotypy while concomitantly increasing the number of nonreinforced responses. Intermediate to relatively high doses of haloperidol antagonized stereotypy and the response inhibition produced by apomorphine. High doses of haloperidol antagonized stereotypy but also suppressed self-stimulation. Thus, haloperidol is not only able to restore performance capability, but also disturbed reinforcing and discriminative stimulus control.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Bromperidol ; Haloperidol ; Chlorpromazine ; Preclinical review ; Animal pharmacology ; Animal pharmacokinetics ; Animal biotransformation ; Animal drug safety
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This review compares and contrasts the preclinical pharmacology of bromperidol with another butyrophenone neuroleptic, haloperidol, and the phenothiazine neuroleptic chlorpromazine. Its pharmacokinetics, biotransformation, and safety in several laboratory animal species are also summarized. These preclinical data support its use as an antipsychotic agent and show that it is well absorbed following oral administration with an apparent elimination half-life of approximately 24 h, supporting a once-daily dose regimen. Animal toxicity (including acute- and multiple-dose toxicology and reproductive and mutagenicity studies) show that bromperidol is well tolerated.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: 5-HT antagonist ; LSD antagonist ; Drug discrimination ; Anxiety ; 5-HTP ; Head twitch ; Conflict behavior ; Hypothermia ; Ritanserin ; Pirenperone ; Chlordiazepoxide ; Diazepam ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The newly synthesized compound and putative 5-HT2 antagonist ritanserin, but not the structurally related compound R 56413, resembles pirenperone in that it acts as a pure antagonist in an LSD-saline drug discrimination assay in the rat. Ritanserin exceeded pirenperone in terms of behavioral specificity; the lowest effective dose of ritanserin in antagonizing LSD was one order of magnitude higher than that of pirenperone, but the compound depressed rate of operant responding only at doses that were about 1000-fold higher than those at which pirenperone was effective. Ritanserin exerted effects in an open field test which were reminiscent of anxiolytic drug activity in the rat; its effects were greater than those of pirenperone, R 56413 and the benzodiazepines chlordiazepoxide and diazepam. The results of experiments on antagonism of 5-HT-induced hypothermia and of the 5-HTP-induced headtwitch response fail to support the possibility that the putative anxiolytic effects of ritanserin in the rat can be ascribed simply to a pharmacologically defined action at 5-HT receptors.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 97 (1989), S. 206-212 
    ISSN: 1432-2072
    Keywords: LSD-cue ; Drug discrimination ; Risperidone ; Schizophrenia ; 5-HT2-catecholamine antagonism ; LSD antagonism ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Risperidone was studied in a 0.16 mg/kg LSD-saline drug discrimination test procedure. At doses varying from 0.0025 to 0.63 mg/kg, no LSD-like agonist effects were observed. Studies on the antagonism of the LSD-cue indicated that risperidone was able to completely block the discriminative stimulus properties of LSD with a minimum ED50-value of 0.028 mg/kg. Risperidone was also very active over time with reference to LSD antagonism, the ED50s after 2, 4 and 8 h pretreatment being 0.028, 0.064 and 0.44 mg/kg. Response rate reductions were only observed at doses ≧0.16 mg/kg after 1 h and at 0.63 mg/kg after 2 h pretreatment. Four and 8 h after treatment, no rate-reducing effects were apparent at doses up to 2.50 mg/kg. Thus at pretreatment intervals ranging between 2 and 8 h, complete antagonism of LSD without any rate effects was obtained. As compared to other LSD antagonists, risperidone was quantitatively better than setoperone and ritanserin and longer acting than pirenperone. Based on the pharmacological profile of risperidone and the other LSD antagonists, it was concluded that a potent central 5-HT2 and catecholamine antagonism is needed for a potent and complete antagonism of the 0.16 mg/kg LSD-cue. The potential clinical effect of risperidone in the positive and negative symptoms of schizophrenia is discussed.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2072
    Keywords: Haloperidol ; Amphetamine ; Rats ; Noise-Escape ; Shuttle Box ; Skinner Box
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The learning process of two different noise-escape responses—lever pressing and jumping—was studied in the same rats using a shuttle box automatically transformable during the experimental sessions into two Skinner boxes. The effects of different doses of haloperidol and amphetamine were studied in rats overtrained in the two situations. The learning process was slower in the Skinner box than in the shuttle box. To reach the maximum response level in 50% of the rats 13 to 18 training sessions of 5 min were necessary in the shuttle box versus 31 to 36 in the Skinner box. Haloperidol prolonged the latency (T) and reduced the frequency (F and F′) of both lever pressing (L) and jumping responses (J) to about the same extent at the same dose levels (lowest effective dose 0.04 mg/kg s.c.). At 0.005 mg/kg haloperidol slightly increased F′L. At doses lower than 2.5 mg/kg, amphetamine decreased T in both the Skinner and the shuttle box and the ineffective responses (F′) were increased up to 4 to 5 times their control values. The lowest effective dose was 0.16 mg/kg in the shuttle box (F′J) and 0.31 mg/kg in the Skinner box (F′L). At 2.5 mg/kg amphetamine increased T and reduced F.
    Type of Medium: Electronic Resource
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