BPC 157 counteracts QTc prolongation induced by haloperidol, fluphenazine, clozapine, olanzapine, quetiapine, sulpiride, and metoclopramide in rats

Life Sci. 2017 Oct 1:186:66-79. doi: 10.1016/j.lfs.2017.08.006. Epub 2017 Aug 7.

Abstract

Aim: Commonly, neuroleptics and prokinetics induce a prolonged QTc interval. In this study, stable gastric pentadecapeptide BPC 157 counteracts the prolongation of the QTc interval in Wistar rats that underwent daily administration of dopamine neuroleptics or prokinetics. Previously, in rats and mice, BPC 157 counteracted neuroleptic-induced catalepsy and gastric ulcers.

Main methods: To counteract neuroleptic- or prokinetic-induced prolongation of the QTc interval, rats were given a BPC 157 regimen once daily over seven days (10μg, 10ng/kg ip) immediately after each administrations of haloperidol (0.625, 6.25, 12.5, and 25.0mg/kg ip), fluphenazine (0.5, 5.0mg/kg ip), clozapine (1.0, 10.0mg/kg ip), quetiapine (1.0, 10.0mg/kg ip), sulpiride (1.6, 16.0mg/kg ip), metoclopramide (2.5, 25.0mg/kg ip) or (1.0, 10.0mg/kg ip). Controls simultaneously received saline (5ml/kg ip). To assess the ECG presentation before and after neuroleptic/prokinetic medication, the assessment was at 1, 2, 3, 4, 5, 10, 15, 20 and 30min (first administration) as well as at 30min, 60min and 24h (first administration and subsequent administrations) and the ECG recording started prior to drug administration.

Key findings: Since very early, a prolonged QTc interval has been continually noted with haloperidol, fluphenazine, clozapine, olanzapine, quetiapine, sulpiride, and metoclopramide in rats as a central common effect not seen with domperidone. Consistent counteraction appears with the stable gastric pentadecapeptide BPC 157. Thus, BPC 157 rapidly and permanently counteracts the QTc prolongation induced by neuroleptics and prokinetics.

Significance: Pentadecapeptide BPC 157 is suited for counteracting a prolonged QT interval.

Keywords: BPC 157; Neuroleptics; Prokinetics; QT interval; Rats.

MeSH terms

  • Animals
  • Anti-Dyskinesia Agents / adverse effects*
  • Antipsychotic Agents / adverse effects*
  • Dopamine Antagonists / adverse effects*
  • Dose-Response Relationship, Drug
  • Electrocardiography
  • Long QT Syndrome / chemically induced
  • Long QT Syndrome / prevention & control*
  • Male
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / therapeutic use*
  • Proteins / administration & dosage
  • Proteins / therapeutic use*
  • Rats, Wistar
  • Time Factors

Substances

  • Anti-Dyskinesia Agents
  • Antipsychotic Agents
  • Dopamine Antagonists
  • Peptide Fragments
  • Proteins
  • BPC 157