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

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.

The Stable Gastric Pentadecapeptide BPC 157 Pleiotropic Beneficial Activity and Its Possible Relations with Neurotransmitter Activity

“…By BPC 157 therapy, the principle of upgrading minor vessels by prompt activation of the vascular collaterals (i.e., azygos vein direct blood flow delivery) is commonly operative to counteract the occlusion/occlusion-like syndrome, major vascular and multiorgan failure peripherally and centrally induced in rats [ 26 , 27 ]. These were induced with permanent major vessel occlusions, central [ 38 , 39 ] and peripheral [ 40 , 41 , 42 , 43 , 44 , 45 , 46 ], similar noxious procedures [ 47 , 48 , 49 , 50 ], and agents’ applications [ 51 , 52 , 53 , 54 , 55 , 56 ]. These all severely affect endothelium function.…”

“…Likewise, counteracted/attenuated were both local and systemic muscle disabilities following muscle relaxant application (depolarizing neuromuscular blocker [ 81 ] and non-depolarizing neuromuscular blocker (report in preparation)). Additionally, counteracted/attenuated were severe muscle disturbances in rats with abdominal aorta occlusion [ 82 ], tumor cachexia (severe muscle wasting) [ 11 ], and different electrolyte disturbances [ 54 , 83 , 84 , 85 ]. Counteracted/attenuated were neuroleptics (i.e., catalepsy) [ 68 , 70 ], L-arginine (i.e., prolonged miosis) [ 86 ], N(G)-nitro-L-arginine methyl ester (L-NAME) (prolonged miosis, catalepsy) [ 70 , 86 ], and alcohol acute and chronic intoxication [ 63 , 64 ].…”

“…Disabling heart failure recovery as a whole [ 4 ] (myocardial infarction [ 53 ], heart failure [ 87 ], pulmonary hypertension [ 88 ], arrhythmias [ 40 , 41 , 42 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 60 , 81 , 89 , 90 , 91 ], and thrombosis presentation [ 40 , 41 , 42 , 43 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]) was reviewed [ 3 , 4 ]. Smooth muscle function recovery was also reviewed [ 3 , 4 ] (i.e., sphincter dysfunction (pupil [ 86 ], lower esophageal and pyloric sphincter [ 92 , 93 , 94 , 95 , 96 , 97 , 98 , …”

“…Finally, for encephalopathies therapy (see Chapter Nerve-Nerve), acting simultaneously in both the periphery and central nervous system, BPC 157 counteracted various encephalopathies and stomach and liver lesions in non-steroidal anti-inflammatory drugs (NSAIDs)-rats [ 61 , 105 , 106 , 107 , 108 , 109 ] and insulin-rats [ 62 ]. Noteworthy, these were recently combined with the mentioned evidence that BPC 157 therapy by rapidly activated collateral pathways (azygos vein direct blood flow delivery) goes as a particular therapy effect, as counteracted the vascular and multiorgan failure concomitant to various major vessel occlusion and similar various noxious procedures and various agents’ application [ 40 , 41 , 42 , 43 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. This specifically reversed the initiated multicausal noxious circuit of the occlusion/occlusion-like syndrome as a general effect.…”

“…Counteracted were the severe lesions and hemorrhage in the brain, lungs, liver, kidney, and gastrointestinal tract. In particular, progressing thrombosis, both peripherally and centrally, and heart arrhythmias and infarction that would consistently occur were fully counteracted and/or almost annihilated [ 40 , 41 , 42 , 43 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. With these capabilities (already advanced Virchow triad circumstances were counteracted), BPC 157 therapy is effective in conditions of ischemia [ 40 , 41 , 42 , 43 , 47 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ] and in conditions of reperfusion [ 38 , 48 , 76 , 77 , 110 ].…”