Haloperidol-stomach lesions attenuation by pentadecapeptide BPC 157, omeprazole, bromocriptine, but not atropine, lansoprazole, pantoprazole, ranitidine, cimetidine and misoprostol in mice

The focus was on haloperidol (central dopamine antagonist)-stomach lesion, a longly described suitable counterpart of dopamine blocker cysteamine-duod enal lesion. In this, the contribution of blockade of central/peripheral do pamine receptors and prostaglandins synthesis, along with influence of anti ulcer agents was evaluated in mice. Male NMRI Hannnover mice were sacrifice d 24 h after haloperidol (25 mg/kg b.w. i.p., given alone or with saline (h aloperidol+saline) (i) or in combination (ii,iii)). Supporting central dopa mine predominance for haloperidol stomach lesion induction, coadministratio n of peripheral dopamine receptor antagonist domperidone (5 mg/kg i.p.) (ha loperidol+ domperidone) (ii), or prostaglandin synthesis inhibitor indometh acin (10 mg/kg s.c.) (haloperidol+ indomethacin) (iii) did not aggravate th is lesion. (i) In haloperidol+saline challenged mice the lesions were inhib ited by co-administration (/kg i.p.) of a gastric pentadecapeptide BPC 157, GlyGluProProProGlyLysProAlaAspAspAlaGlyLeuVal, M.W. 1419 (10 mug, 10 ng, 1 0 pg, but not 1 pg, 100 fg, 10 fg), bromocriptine (10 mg), omeprazole (10 m g, 100 mg, but not 1 mg). Atropine (10, 100,200 mg), pirenzepine (10, 100, 200 mug),misoprostol (10, 100, 200 mug), pantoprazole (1, 10, 100 mg), lans oprazole (0.1, 1, 10 mg), cimetidine (10, 100, 200 mg) and ranitidine (10, 100, 200 mg) were not effective. (ii) Dopamine peripheral blockade influenc e: in haloperidol+domperidone mice, previously effective bromocriptine, pen tadecapeptide BPC 157 (10 mug) or omeprazole (10 mg) did not attenuate stom ach lesions. (iii) Prostaglandins synthesis blockade effect: in haloperidol +indomethacin mice, previously effective agents, bromocriptine or omeprazol e were not active, while BPC 157 effect was only lessened. (C) 2001 Elsevie r Science Inc. All rights reserved.