Departments of Pharmacology & Pathology, Medical Faculty University of Zagreb, Zagreb, Croatia; Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia.
Departments of Pharmacology & Pathology, Medical Faculty University of Zagreb, Zagreb, Croatia; Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia.
Life Sci. 2017 Oct 1;186:66-79. doi: 10.1016/j.lfs.2017.08.006. Epub 2017 Aug 7.
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.
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.
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.
Pentadecapeptide BPC 157 is suited for counteracting a prolonged QT interval.
通常情况下，神经安定药和促动力药会导致 QTc 间期延长。在这项研究中，稳定的胃十五肽 BPC 157 可对抗接受多巴胺神经安定药或促动力药每日给药的 Wistar 大鼠的 QTc 间期延长。此前，BPC 157 已在大鼠和小鼠中对抗了神经安定药引起的僵住和胃溃疡。
为了对抗神经安定药或促动力药引起的 QTc 间期延长，大鼠在连续 7 天内每天接受一次 BPC 157 治疗方案（10μg、10ng/kg 腹腔注射），在每次给予氟哌啶醇（0.625、6.25、12.5 和 25.0mg/kg 腹腔注射）、氟奋乃静（0.5、5.0mg/kg 腹腔注射）、氯氮平（1.0、10.0mg/kg 腹腔注射）、喹硫平（1.0、10.0mg/kg 腹腔注射）、舒必利（1.6、16.0mg/kg 腹腔注射）、甲氧氯普胺（2.5、25.0mg/kg 腹腔注射）或（1.0、10.0mg/kg 腹腔注射）后立即给予。对照组同时接受生理盐水（5ml/kg 腹腔注射）。为了评估神经安定药/促动力药给药前后的心电图表现，在第一次给药后 1、2、3、4、5、10、15、20 和 30min 以及第一次给药后 30min、60min 和 24h 进行评估，在给药前开始进行心电图记录。
从早期开始，氟哌啶醇、氟奋乃静、氯氮平、奥氮平、喹硫平、舒必利和甲氧氯普胺在大鼠中一直持续出现 QTc 间期延长，这是一种中枢共同作用，在多潘立酮中未观察到。稳定的胃十五肽 BPC 157 持续发挥拮抗作用。因此，BPC 157 可快速且永久地拮抗神经安定药和促动力药引起的 QTc 延长。
十五肽 BPC 157 适合对抗 QTc 间期延长。
