Pentadecapeptide BPC 157 attenuates disturbances induced by neuroleptics: the effect on catalepsy and gastric ulcers in mice and rats

A gastric pentadecapeptide, BPC 157, with the amino acid sequence, Gly-Glu- Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val, MW 1419, known to have a variety of protective effects in gastrointestinal tract and other organs , was recently shown to particularly affect dopamine systems. For instance, it blocks the stereotypy produced acutely by amphetamine in rats, and the development of haloperidol-induced supersensitivity to amphetamine in mice. Consequently, whether pentadecapeptide BPC 157, that by itself has no cata leptogenic effect in normal animals, may attenuate the immediate effects of neuroleptics application, particularly catalepsy, was the focus of the pre sent report. Prominent catalepsy, otherwise consistently seen in the mice t reated with haloperidol (0.625, 1.25, 2.5, 5.0 and 10.0 mg/kg b.w., i.p.) a nd fluphenazine (0.3125, 0.625, 1.25, 2.5 and 5.0 mg/kg b.w., i.p.) after 1 .5, 3, 4.5, 6 and 7.5 h following administration, was markedly attenuated w hen pentadecapeptide BPC 157 (10 mu g or 10 ng/kg b.w., i.p.) was coadminis tered with the neuroleptic. The number of cataleptic mice was markedly lowe r throughout most of the experimental period. Moreover, on challenge with l ower doses of neuroleptics, catalepsy appearance was postponed and the mice , otherwise cataleptic since the earliest period, became cataleptic later, not before 3 or 4.5 h after neuroleptic administration, especially if prote cted with higher pentadecapeptide dose. Besides catalepsy, coadministration of the pentadecapeptide BPC 157, given in the abovementioned doses, reduce d not only catalepsy but somatosensory disorientation (for 7.5 h after admi nistration of a neuroleptic, assessed at intervals of 1.5 h, by a simple sc oring system [0-5]) in haloperidol- or fluphenazine-challenged mice as it d id in mice treated with sulpiride (20, 40, 80 and 160 mg/kg b.w., i.p.) or with clozapine (25, 50 and 100 mg/kg b.w., i.p.), in which case catalepsy w as absent. In other experiments, considering the gastric origin of this pen tadecapeptide, the focus was shifted to the evidence that a dose of haloper idol, cataleptogenic due to dopamine receptors blockade, induces gastric ul cers in rats. Coadministration of pentadecapeptide BPC 157 (10 mu g, 10 ng, 1.0 ng, 100 pg/kg b.w., i.p.) to rats completely inhibited the lesions oth erwise regularly evident 24 h after haloperidol (5.0 mg/kg b.w., i.p.) in c ontrol rats (18 of 20 rats had gastric lesions). This activity accompanied the antagonism of the haloperidol catalepsy in rats (assessed at 60-min int ervals from 1 to 5 h after haloperidol), when 10-mu g- or 10-ng regimens we re given (lower doses could not influence catalepsy). Together, these findi ngs indicate that pentadecapeptide BPC 157 fully interacts with the dopamin e system, both centrally and peripherally, or at least, that BPC 157 interf eres with some steps involved in catalepsy and/or ulcer formation. (C) 1999 Elsevier Science B.V. All rights reserved.