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-duodenal lesion. In this, the contribution of blockade of central/peripheral dopamine receptors and prostaglandins synthesis, along with influence of antiulcer agents was evaluated in mice. Male NMRI Hannnover mice were sacrificed 24 h after haloperidol (25 mg/kg b.w. i.p., given alone or with saline (haloperidol+saline) (i) or in combination (ii,iii)). Supporting central dopamine predominance for haloperidol stomach lesion induction, co-administration of peripheral dopamine receptor antagonist domperidone (5 mg/kg i.p.) (haloperidol+ domperidone) (ii), or prostaglandin synthesis inhibitor indomethacin (10 mg/kg s.c.) (haloperidol+ indomethacin) (iii) did not aggravate this lesion. (i) In haloperidol+saline challenged mice the lesions were inhibited by co-administration (/kg i.p.) of a gastric pentadecapeptide BPC 157, GlyGluProProProGlyLysProAlaAspAspAlaGlyLeuVal, M.W. 1419 (10 microg, 10 ng, 10 pg, but not 1 pg, 100 fg, 10 fg), bromocriptine (10 mg), omeprazole (10 mg, 100 mg, but not 1 mg). Atropine (10, 100, 200 mg), pirenzepine (10, 100, 200 mg), misoprostol (10, 100, 200 microg), pantoprazole (1, 10, 100 mg), lansoprazole (0.1, 1, 10 mg), cimetidine (10, 100, 200 mg) and ranitidine (10, 100, 200 mg) were not effective. (ii) Dopamine peripheral blockade influence: in haloperidol+domperidone mice, previously effective bromocriptine, pentadecapeptide BPC 157 (10 microg) or omeprazole (10 mg) did not attenuate stomach lesions. (iii) Prostaglandins synthesis blockade effect: in haloperidol+indomethacin mice, previously effective agents, bromocriptine or omeprazole were not active, while BPC 157 effect was only lessened.
Bilic
I
I
Medical Faculty University of Zagreb, Croatia.
Zoricic
I
I
Anic
T
T
Separovic
J
J
Stancic-Rokotov
D
D
Mikus
D
D
Buljat
G
G
Ivankovic
D
D
Aralica
G
G
Prkacin
I
I
Perovic
D
D
Mise
S
S
Rotkvic
I
I
Petek
M
M
Rucman
R
R
Seiwerth
S
S
Sikiric
P
P
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001285:Atropine / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use; D001971:Bromocriptine / Q000627:therapeutic use; D002927:Cimetidine / Q000627:therapeutic use; D004195:Disease Models, Animal; D004294:Domperidone / Q000008:administration & dosage; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006220:Haloperidol / Q000008:administration & dosage / Q000633:toxicity*; D007213:Indomethacin / Q000008:administration & dosage; D064747:Lansoprazole; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016595:Misoprostol / Q000627:therapeutic use; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077402:Pantoprazole; D010446:Peptide Fragments / Q000627:therapeutic use; D011506:Proteins / Q000627:therapeutic use; D011899:Ranitidine / Q000627:therapeutic use; D013272:Stomach Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D013454:Sulfoxides / Q000627:therapeutic use
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D018492:Dopamine Antagonists; D010446:Peptide Fragments; D011506:Proteins; D013454:Sulfoxides; D016595:Misoprostol; D064747:Lansoprazole; D001971:Bromocriptine; D004294:Domperidone; D001285:Atropine; D002927:Cimetidine; D011899:Ranitidine; C083833:BPC 157; D000077402:Pantoprazole; D006220:Haloperidol; D009853:Omeprazole; D007213:Indomethacin