Class side effects: decreased pressure in the lower oesophageal and the pyloric sphincters after the administration of dopamine antagonists, neuroleptics, anti-emetics, l-NAME, pentadecapeptide BPC 157 and l-arginine

Abstract

The ulcerogenic potential of dopamine antagonists and L-NAME in rats provides unresolved issues of anti-emetic neuroleptic application in both patients and experimental studies. Therefore, in a 1-week study, we examined the pressures within the lower oesophageal and the pyloric sphincters in rats [assessed manometrically (cm HO)] after dopamine neuroleptics/prokinetics, L-NAME, L-arginine and stable gastric pentadecapeptide BPC 157 were administered alone and/or in combination. Medication (/kg) was given once daily intraperitoneally throughout the 7 days, with the last dose at 24 h before pressure assessment. Given as individual agents to healthy rats, all dopamine antagonists (central [haloperidol (6.25 mg, 16 mg, 25 mg), fluphenazine (5 mg), levomepromazine (50 mg), chlorpromazine (10 mg), quetiapine (10 mg), olanzapine (5 mg), clozapine (100 mg), sulpiride (160 mg), metoclopramide (25 mg)) and peripheral(domperidone (10 mg)], L-NAME (5 mg) and L-arginine (100 mg) decreased the pressure within both sphincters. As a common effect, this decreased pressure was rescued, dose-dependently, by BPC 157 (10 µg, 10 ng) (also note that L-arginine and L-NAME given together antagonized each other's responses). With haloperidol, L-NAME worsened both the lower oesophageal and the pyloric sphincter pressure, while L-arginine ameliorated lower oesophageal sphincter but not pyloric sphincter pressure, and antagonized L-NAME effect. With domperidone, L-arginine originally had no effect, while L-NAME worsened pyloric sphincter pressure. This effect was opposed by L-arginine. All these effects were further reversed towards a stronger beneficial effect, close to normal pressure values, by the addition of BPC 157. In addition, NO level was determined in plasma, sphincters and brain tissue. Thiobarbituric acid reactive substances (TBARS) were also assessed. Haloperidol increased NO levels (in both sphincters, the plasma and brain), consistently producing increased TBARS levels in the plasma, sphincters and brain tissues. These effects were all counteracted by BPC 157 administration. In conclusion, we revealed that BPC 157 counteracts the anti-emetic neuroleptic class side effect of decreased pressure in sphincters and the dopamine/NO-system/BPC 157 relationship.

Stable Gastric Pentadecapeptide BPC 157, Robert's Stomach Cytoprotection/Adaptive Cytoprotection/Organoprotection, and Selye's Stress Coping Response: Progress, Achievements, and the Future

“…[1][2][3][4][5][6][7][8][9][10][11][12][13] BPC 157 also acts as a free radical scavenger, counteracts free radical-induced lesions, and normalizes NO and MDA levels in tissues and during ischemia and reperfusion. 101,113,114,[116][117][118] Subsequent studies from other groups 2,96-101 have confirmed our original findings. [65][66][67][68][69][70][71][72][73][74][75][76][77][78] Pleotropic effects involving distinctive receptors, including VEGFR2 and growth hormone receptors, distinctive pathways, including VEGFR2-AKT-eNOS, ERK ½, FAK-paxillin, FoxO3a, p-AKT, p-mTOR and p-GSK-3β, and distinctive loops, including stimulation of the egr-1 gene and its corepressor gene naB2, and counteraction of increases in pro-inflammatory and procachectic cytokines, 2,[96][97][98][99][100][101] likely minimize the inherent lack of full understanding of the mechanisms that may be involved.…”

“…41,114 The notation that BPC 157-NOsystem-relation interferes with the effects of neuroleptics merits further elaboration. 115,116 Finally, BPC 157 application lead to normalization of NO-level in tissues as well as counteraction of free-radicals formation. 113,114,116 Of note, how this advantage of modulating NO-system (i.e., particular effect on eNOS gene), may be a practical background which could be further translated into an enhanced clinical performance.…”

“…115,116 Finally, BPC 157 application lead to normalization of NO-level in tissues as well as counteraction of free-radicals formation. 113,114,116 Of note, how this advantage of modulating NO-system (i.e., particular effect on eNOS gene), may be a practical background which could be further translated into an enhanced clinical performance. [1][2][3][4][5][6][7][8][9][10][11][12][13] BPC 157 may have a particular additional effect during the injury on the blood vessel activity: vessel recruitment to circumvent the vessel occlusion…”

Stable gastric pentadecapeptide BPC 157 in honeybee (Apis mellifera) therapy, to control Nosema ceranae invasions in apiary conditions

“…Therefore, the antioxidant system may play an essential role during midgut invasion, which is however, largely disabled in invaded honeybees (Dussaubat et al, 2012). Thus, although this was not specifically investigated in insect midgut, it should be noted that various free radicals-induced lesions in other organs were also counteracted by BPC 157 administration (Ilic et al, 2010;Luetic et al, 2017;, and in particular, ischemia/reperfusion injuries in rat colitis (Duzel et al, 2017). Thus, it was suggested that BPC 157 may serve as a possible antioxidant (i.e., BPC 157 contains four carboxylic groups, all of them could be active in scavenger process and if reactivated [e.g., by glutathione or by enzymes], the overall beneficial activity could be very high; Duzel et al, 2017).…”

Stable gastric pentadecapeptide BPC 157 can improve the healing course of spinal cord injury and lead to functional recovery in rats

“…In summary, this effect may be the cause or a consequence of the beneficial effects of BPC 157 on related disturbances [1][2][3][4][5][6][7][8][9][10][11]. As demonstrated, BPC 157 counteracts free radical formation and free radical-induced lesions [32,[82][83][84]. An interesting point would be the use of the same dose range in BPC 157 studies [1][2][3][4][5][6][7][8][9][10][11].…”