, Volume 25, Issue 5, pp 511–522 | Cite as

Class side effects: decreased pressure in the lower oesophageal and the pyloric sphincters after the administration of dopamine antagonists, neuroleptics, anti-emetics, l-NAME, pentadecapeptide BPC 157 and l-arginine

  • Zeljka Belosic Halle
  • Josipa Vlainic
  • Domagoj Drmic
  • Dean Strinic
  • Kresimir Luetic
  • Mario Sucic
  • Maria Medvidovic-Grubisic
  • Tatjana Pavelic Turudic
  • Igor Petrovic
  • Sven Seiwerth
  • Predrag SikiricEmail author
Original Article


The ulcerogenic potential of dopamine antagonists and l-NAME in rats provides unresolved issues of anti-emetic neuroleptic application in both patients and experimental studies. Therefore, in a 1-week study, we examined the pressures within the lower oesophageal and the pyloric sphincters in rats [assessed manometrically (cm H2O)] after dopamine neuroleptics/prokinetics, l-NAME, l-arginine and stable gastric pentadecapeptide BPC 157 were administered alone and/or in combination. Medication (/kg) was given once daily intraperitoneally throughout the 7 days, with the last dose at 24 h before pressure assessment. Given as individual agents to healthy rats, all dopamine antagonists (central [haloperidol (6.25 mg, 16 mg, 25 mg), fluphenazine (5 mg), levomepromazine (50 mg), chlorpromazine (10 mg), quetiapine (10 mg), olanzapine (5 mg), clozapine (100 mg), sulpiride (160 mg), metoclopramide (25 mg)) and peripheral(domperidone (10 mg)], l-NAME (5 mg) and l-arginine (100 mg) decreased the pressure within both sphincters. As a common effect, this decreased pressure was rescued, dose-dependently, by BPC 157 (10 µg, 10 ng) (also note that l-arginine and l-NAME given together antagonized each other’s responses). With haloperidol, l-NAME worsened both the lower oesophageal and the pyloric sphincter pressure, while l-arginine ameliorated lower oesophageal sphincter but not pyloric sphincter pressure, and antagonized l-NAME effect. With domperidone, l-arginine originally had no effect, while l-NAME worsened pyloric sphincter pressure. This effect was opposed by l-arginine. All these effects were further reversed towards a stronger beneficial effect, close to normal pressure values, by the addition of BPC 157. In addition, NO level was determined in plasma, sphincters and brain tissue. Thiobarbituric acid reactive substances (TBARS) were also assessed. Haloperidol increased NO levels (in both sphincters, the plasma and brain), consistently producing increased TBARS levels in the plasma, sphincters and brain tissues. These effects were all counteracted by BPC 157 administration. In conclusion, we revealed that BPC 157 counteracts the anti-emetic neuroleptic class side effect of decreased pressure in sphincters and the dopamine/NO-system/BPC 157 relationship.


BPC 157 Dopamine antagonists Neuroleptics NO-system Rats 



This research was supported by the Ministry of Science, Education and Sports, Republic of Croatia (Grant Number 108-1083570-3635).


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Copyright information

© Springer International Publishing 2017

Authors and Affiliations

  • Zeljka Belosic Halle
    • 1
    • 4
  • Josipa Vlainic
    • 2
  • Domagoj Drmic
    • 1
  • Dean Strinic
    • 1
    • 4
  • Kresimir Luetic
    • 1
    • 4
  • Mario Sucic
    • 1
    • 4
  • Maria Medvidovic-Grubisic
    • 1
  • Tatjana Pavelic Turudic
    • 1
    • 4
  • Igor Petrovic
    • 1
  • Sven Seiwerth
    • 3
  • Predrag Sikiric
    • 1
    Email author
  1. 1.Department of Pharmacology, School of MedicineUniversity of ZagrebZagrebCroatia
  2. 2.Laboratory of Molecular Neuropharmacology, Division of Molecular MedicineRudjer Boskovic InstituteZagrebCroatia
  3. 3.Department of Pathology, School of MedicineUniversity of ZagrebZagrebCroatia
  4. 4.Faculty of MedicineJ.J. Strossmayer University of OsijekOsijekCroatia

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