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

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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 (10 μg, 10 ng/kg ip) immediately after each administrations of haloperidol (0.625, 6.25, 12.5, and 25.0 mg/kg ip), fluphenazine (0.5, 5.0 mg/kg ip), clozapine (1.0, 10.0 mg/kg ip), quetiapine (1.0, 10.0 mg/kg ip), sulpiride (1.6, 16.0 mg/kg ip), metoclopramide (2.5, 25.0 mg/kg ip) or (1.0, 10.0 mg/kg ip). Controls simultaneously received saline (5 ml/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 30 min (first administration) as well as at 30 min, 60 min and 24 h (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.

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