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应用抗精神病药、苯丙胺和多潘立酮导致的先天性血管功能衰竭迅速在大鼠中诱发严重闭塞/类闭塞综合征,稳定的胃十五肽BPC 157作为治疗药物。

Innate Vascular Failure by Application of Neuroleptics, Amphetamine, and Domperidone Rapidly Induced Severe Occlusion/Occlusion-like Syndromes in Rats and Stable Gastric Pentadecapeptide BPC 157 as Therapy.

作者信息

Strbe Sanja, Smoday Ivan Maria, Krezic Ivan, Kalogjera Luka, Vukovic Vlasta, Zizek Helena, Gojkovic Slaven, Vranes Hrvoje, Barisic Ivan, Sikiric Suncana, Tepes Marijan, Oroz Katarina, Brkic Filip, Drinkovic Martin, Beketic Oreskovic Lidija, Popic Jelena, Boban Blagaic Alenka, Skrtic Anita, Staresinic Mario, Seiwerth Sven, Sikiric Predrag

机构信息

Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.

Department of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.

出版信息

Pharmaceuticals (Basel). 2023 May 25;16(6):788. doi: 10.3390/ph16060788.

DOI:10.3390/ph16060788
PMID:37375736
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10303627/
Abstract

Even before behavioral disturbances, neuroleptics, amphetamine, and domperidone application rapidly emerged severe occlusion/occlusion-like syndrome, shared innate vascular and multiorgan failure in rats, comparable to occlusion/occlusion-like syndrome described with vessel(s) occlusion or similar noxious procedures application. As therapy, i.e., activation of the collateral pathways, "bypassing key" (activated azygos vein pathway, direct blood flow delivery), the stable gastric pentadecapeptide BPC 157 is a novel solution. Recently, BPC 157 therapy particularly counteracted neuroleptic- or L-NAME-induced catalepsy, lithium intoxication, and schizophrenia positive and negative symptoms (amphetamine/methamphetamine/apomorphine/ketamine). In rats with complete calvariectomy, medication (BPC 157 10 µg/kg, 10 ng/kg ip or ig) was given 5 min after distinctive dopamine agents (mg/kg ip) (haloperidol (5), fluphenazine (5), clozapine (10), risperidone (5), olanzapine (10), quetiapine (10), or aripiprazole (10), domperidone (25), amphetamine (10), and combined amphetamine and haloperidol) and assessed at 15 min thereafter. All neuroleptic-, domperidone-, and amphetamine-induced comparable vascular and multiorgan failure severe syndrome was alleviated with BPC 157 therapy as before major vessel(s) occlusion or other similar noxious procedures. Specifically, all severe lesions in the brain (i.e., immediate swelling, hemorrhage), heart (i.e., congestion, arrhythmias), and lung (i.e., congestion, hemorrhage), as well as congestion in the liver, kidney, and gastrointestinal (stomach) tract, were resolved. Intracranial (superior sagittal sinus), portal, and caval hypertension and aortal hypotension were attenuated or eliminated. BPC 157 therapy almost annihilated arterial and venous thrombosis, peripherally and centrally. Thus, rapidly acting Virchow triad circumstances that occur as dopamine central/peripheral antagonists and agonist essential class-points, fully reversed by BPC 157 therapy, might be overwhelming for both neuroleptics and amphetamine.

摘要

甚至在出现行为障碍之前,应用抗精神病药物、苯丙胺和多潘立酮后,大鼠迅速出现严重的闭塞/类闭塞综合征,伴有先天性血管和多器官功能衰竭,这与因血管闭塞或类似有害操作所描述的闭塞/类闭塞综合征相似。作为治疗方法,即激活侧支循环途径,“绕过关键部位”(激活奇静脉途径,直接输送血流),稳定的胃十五肽BPC 157是一种新的解决方案。最近,BPC 157治疗特别对抗了抗精神病药物或L-精氨酸甲酯诱导的僵住症、锂中毒以及精神分裂症的阳性和阴性症状(苯丙胺/甲基苯丙胺/阿扑吗啡/氯胺酮)。在完全颅骨切除的大鼠中,在给予不同的多巴胺药物(毫克/千克,腹腔注射)(氟哌啶醇(5)、氟奋乃静(5)、氯氮平(10)、利培酮(5)、奥氮平(10)、喹硫平(10)或阿立哌唑(10)、多潘立酮(25)、苯丙胺(10)以及苯丙胺与氟哌啶醇联合使用)5分钟后给予药物(BPC 157 10微克/千克,10纳克/千克,腹腔注射或灌胃),并在15分钟后进行评估。与主要血管闭塞或其他类似有害操作之前一样,BPC 157治疗缓解了所有抗精神病药物、多潘立酮和苯丙胺诱导的类似血管和多器官功能衰竭的严重综合征。具体而言,大脑中的所有严重病变(即立即肿胀、出血)、心脏(即充血、心律失常)和肺部(即充血、出血),以及肝脏、肾脏和胃肠道(胃)的充血均得到解决。颅内(上矢状窦)、门静脉和腔静脉高压以及主动脉低血压得到减轻或消除。BPC 157治疗几乎消除了外周和中枢的动脉和静脉血栓形成。因此,作为多巴胺中枢/外周拮抗剂和激动剂的基本类要点而出现的快速起效的维氏三联征情况,被BPC 157治疗完全逆转,这对抗精神病药物和苯丙胺来说可能都是压倒性的。

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10
Fatal pulmonary embolism in patients on antipsychotics: case series, systematic review and meta-analysis.抗精神病药物治疗患者的致命性肺栓塞:病例系列、系统评价和荟萃分析。
Asian J Psychiatr. 2022 Jul;73:103105. doi: 10.1016/j.ajp.2022.103105. Epub 2022 Apr 12.