Abstract
Apomorphine was administered to dogs 1, 3 and 20 h after pretreatment with thioridazine, haloperidol or pimozide. The dogs were observed for emesis, stereotypy and side effects of the neuroleptics. All three neuroleptics effectively blocked emesis and stereotypy; haloperidol in doses as low as 0.0125 mg/kg for stereotypy and 0.050 mg/kg for emesis; pimozide, 0.025 mg/kg for stereotypy, and 0.00625 mg/kg for emesis; and thioridazine, 4.0 mg/kg for both effects.
Haloperidol 0.050 mg/kg blocked emesis and stereotypy at 1 h, but the same dose of pimozide blocked only emesis at this time. Threshold doses (0.0125 mg/kg) of haloperidol blocked stereotypy but not emesis, whereas the same dose of pimozide blocked emesis but not stereotypy. A marked tremor and a gnawing syndrome were seen with haloperidol 0.050 mg/kg, but did not appear with pimozide until higher doses were administered; these side effects were not observed with thioridazine.
The findings support a dopaminergic mechanism for apomorphine induced stereotypy in dogs. Differences in onset of pimozide and haloperidol suggest different permeabilities of the drugs through the blood brain barrier, as well as differences in accessibility of the chemoreceptor trigger zone and corpus striatum to circulating drugs. The different effects of threshold doses of pimozide and haloperidol may be explained by postulating the existence of two dopamine receptors.
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Supported by USPHS Grant MH 12383.
This project was part of the fourth year medical student elective program.
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Rotrosen, J., Wallach, M.B., Angrist, B. et al. Antagonism of apomorphine-induced stereotypy and emesis in dogs by thioridazine, haloperidol, and pimozide. Psychopharmacologia 26, 185–194 (1972). https://doi.org/10.1007/BF00422105
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DOI: https://doi.org/10.1007/BF00422105