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


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 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Andén NE (1972) Dopamine turnover in the corpus striatum and the limbic system after treatment with neuroleptic and anti-acetylcholine drugs. J Pharm Pharmacol 24:905–906Google Scholar
  2. Andén NE, Stock G (1973) Effect of clozapine on the turnover of dopamine in the corpus striatum and in the limbic system. J Pharm Pharmacol 25:346–348Google Scholar
  3. Andén NE, Roos BE, Werdinius B (1963) On the occurrence of homovanillic acid in brain and cerebrospinal fluid and its determination by a fluorometric method. Life Sci 2:448–458Google Scholar
  4. Andén NE, Roos BE, Werdinius B (1964) Effects of chlorpromazine, haloperidol and reserpine on the levels of phenolic acids in rabbit corpus striatum. Life Sci 3:149–158Google Scholar
  5. Borenstein P, Champion C, Cujo Ph, Gekiers P, Olivenstein C, Kramarz P (1969) An original psychotropic drug: sulpiride. Sem Hop Paris 19:1301–1314Google Scholar
  6. Burki HR, Ruch W, Asper H (1975) Effects of clozapine, thioridazine, perlapine and haloperidol on the metabolism of the biogenic amines in the brain of the rat. Psychopharmacol 41:27–33Google Scholar
  7. Cooper BR, Breese GR, Grant LD, Howard JL (1973) Effects of 6-hydroxydopamine treatments on active avoidance responding: evidence for involvement of brain dopamine. J Pharmacol Exp Ther 185:358–370Google Scholar
  8. Costall B, Naylor RJ (1975) Detection of the neuroleptic properties of clozapine, sulpiride and thioridazine. Psychopharmacol 43:69–74Google Scholar
  9. Costall B, Naylor RJ (1976) A comparison of the abilities of typical neuroleptic agents and of thioridazine, clozapine, sulpiride and metoclopramide to antagonize the hyperactivity induced by dopamine applied intracerebrally to areas of the extrapyramidal and mesolimbic systems. Eur J Pharmacol 40:9–19Google Scholar
  10. Costall B, Fortune DH, Naylor RJ (1978) Differential activities of some benzamide derivatives on peripheral and intracerebral administration. J Pharm Pharmacol 30:796–798Google Scholar
  11. Elliott PNC, Jenner P, Huizing G, Marsden CD, Miller R (1977) Substituted benzamides as cerebral dopamine antagonists in rodents. Neuropharmacology 16:333–342Google Scholar
  12. Honda F, Satoh Y, Shimomura K, Satoh H, Noguchi H, Uchida S, Kato R (1977) Dopamine receptor blocking activity of sulpiride in the central nervous system. Jpn J Pharmacol 27:397–411Google Scholar
  13. Jenner P, Clow A, Reavill C, Theodorou A, Marsden CD (1978) A behavioural and biochemical comparison of dopamine receptor blockade by haloperidol with that produced by substituted benzamide drugs. Life Sci 23:545–550Google Scholar
  14. König JF, Klippel RA (1963) The rat brain. Williams and Wilkins Co, Baltimore, pp 1–5Google Scholar
  15. Kuribara H, Tadokoro S (1980) Correlation between antiavoidance activities of antipsychotic drugs in rats and daily clinical doses. Pharmacol Biochem Behav 14:181–192Google Scholar
  16. Meltzer HY, So R, Miller RJ, Fang VS (1979) Comparison of the effects of substituted benzamides and standard neuroleptics on the binding of 3H-spiroperidol in the rat pituitary and striatum with in vivo effects on rat prolactin secretion. Life Sci 25:573–584Google Scholar
  17. Nakara BRS, Bond AJ, Lader HM (1975) Comparative psychotropic effects of metoclopramide and prochlorperazine in normal subjects. J Clin Pharmacol 15:449–454Google Scholar
  18. Peringer E, Jenner P, Marsden CD (1975) Effect of metoclopramide on turnover of brain dopamine, noradrenaline and 5-hydroxytryptamine. J Pharm Pharmacol 27:442–444Google Scholar
  19. Rotrosen J, Stanley M, Lautin A, Wazer D, Gershon S (1981) Discrimination of functionally heterogeneous receptor subpopulation: antipsychotic and antidopaminergic properties of metoclopramide. Psychopharmacology Bulletin 17:110–113Google Scholar
  20. Scatton B (1982) Effect of dopamine agonists and neuroleptic agents on striatal acetylcholine transmission in the rat: evidence against dopamine receptor multiplicity. J Pharmacol Exp Ther 220:197–202Google Scholar
  21. Smith RD, Cooper BR, Breese GR (1973) Growth and behavioral changes in developing rats treated intracisternally with 6-hydroxydopamine: evidence for involvement of brain dopamine. J Pharmacol Exp Ther 185:609–619Google Scholar
  22. Stanley M, Rotrosen J, Lautin A, Wazer D, Gershon S (1979) Tardive dyskinesia and metoclopramide. Lancet 11:1190Google Scholar
  23. Stanley M, Lautin A, Rotrosen J, Gershon S, Kleinberg D (1980) Metoclopramide: antipsychotic efficacy of a drug lacking potency in receptor models. Psychopharmacol 71:219–225Google Scholar
  24. Stawarz RJ, Hill H, Robinson SE, Setler P, Dingell JV, Sulser F (1975) On the significance of the increase in homovanillic acid (HVA) caused by antipsychotic drugs in corpus striatum and limbic forebrain. Psychopharmacol 43:125–130Google Scholar
  25. Tagliamonte A, De Montis G, Olianas M, Vargiu L, Corsini GU, Gessa GL (1975) Selective increase of brain dopamine synthesis by sulpiride. J Neurochem 24:707–710Google Scholar

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

Personalised recommendations