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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 321, Issue 3, pp 190–194 | Cite as

Differential effects of sulpiride and metoclopramide on brain

Homovanillic acid levels and shuttle box avoidance after systemic and intracerebral administration
  • Yasuhiro Nishibe
  • Yoshikazu Matsuo
  • Toshio Yoshizaki
  • Masami Eigyo
  • Teruo Shiomi
  • Katsumi Hirose
Article

Summary

Sulpiride (SUL) is more efficacious in antipsychotic activity than metoclopramide (MET), although both appear to possess almost equal affinities for dopamine (DA) receptors. We studied the effects of SUL and MET on the brain homovanillic acid (HVA) level and shuttle box avoidance to clarify their differential modes of action on the blockade of DA receptors. SUL was several times less potent than MET, which was about 50 times less potent than the control drug haloperidol (HAL), for increasing HVA at 4 h after s.c. administration. However, SUL was about 50 times more potent than MET and about equipotent to HAL, at 2 h after drug administration into the lateral ventricle. The potency of SUL by intraventricular administration was 20-fold or more than that by intracisternal administration. HAL and MET did not show such a discrepancy. The HVA level reached the maximum 1 h after intraventricular administration of MET or HAL, while s.c., intracisternal or intraventricular administration of SUL caused a gradual increase in the HVA level with the maximum being reached after 6–8 h. In shuttle box avoidance, MET was about 25 times more potent than SUL by intraperitoneal administration but about 200 times less potent than SUL, which was about 10 times more potent than HAL, by intraventricular administration. These results suggest that SUL causes a potent, long-lasting blockade of DA receptors, while MET has only a weak, short-lasting action. These findings may be related to the differences in their clinical efficacy.

Key words

Striatum Limbic forebrain HVA Shuttle box avoidance Intraventricular administration 

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Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • Yasuhiro Nishibe
    • 1
  • Yoshikazu Matsuo
    • 1
  • Toshio Yoshizaki
    • 1
  • Masami Eigyo
    • 2
  • Teruo Shiomi
    • 2
  • Katsumi Hirose
    • 3
  1. 1.Kanzakigawa Laboratory, Shionogi Research LaboratoriesShionogi and Co., Ltd.Toyonaka-shi, OsakaJapan
  2. 2.Aburahi Laboratories, Shionogi Research LaboratoriesShionogi and Co., Ltd.ShigaJapan
  3. 3.Shionogi Research LaboratoriesShionogi and Co., Ltd.OsakaJapan

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