Synthesis, gastroprotective, antisecretory and anti-Helicobacter effect of N-[3-(3-(1-piperidinylmethyl) phenoxy)propyl]-hydroxyacetamide 2-hydroxypropane-1,2,3-tricarboxylate bismuth (3+) complex (MX1)-MX1.
MX1 (N-[3-(3-(1-piperidinylmethyl)phenoxy)propyl]-hydroxyacetamide+ ++ 2-hydroxypropane-1,2,3-tricarboxylate bismuth (3+) complex) is a novel salt of the active metabolite of H2-antagonist roxatidine with a complex of bismuth with citric acid. In a model of ethanol-induced ulcers in male Wistar rats, both roxatidine and the bismuth salt reduced the number and the total length of lesions. Comparison of roxatidine and MX1 at equimolar doses of 160 mumol kg-1 showed a more potent cytoprotective effect of MX1. The potency of anti-secretory and antiacidic effects of MX1 was more than twice that of roxatidine on histamine-stimulated secretion in female Wistar pylorus-ligated rats. Microbiological tests with the reference bismuth preparation De-Nol showed prominent anti-Helicobacter properties of MX1 in-vitro. Both test compounds had similar range of MICs to Helicobacter pylori, from 4 to 64 microgram bismuth mL-1. The cytoprotective, antisecretory, anti-acidic and anti-Helicobacter properties of the new agent MX1 warrant further more extensive pharmacological and clinical trials.
Ivanov
C
C
Chemical Pharmaceutical Research Institute, Military Medical Academy, Sofia, Bulgaria.
Petkov
O
O
Petrov
P
P
Taskov
M
M
Athanassova
R
R
Tsvetkova
E
E
Kotsev
V
V
Lyutakov
G
G
Nikolov
G
G
Savov
E
E
D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000431:Ethanol; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D016480:Helicobacter pylori / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D008297:Male; D008826:Microbial Sensitivity Tests; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy / Q000382:microbiology; D014233:Tricarboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*
D000897:Anti-Ulcer Agents; C103277:N-(3-(3-(1-piperidinyl-methyl)phenoxy)propyl)hydroxyacetamide 2-hydroxypropane-1,2,3-tricarboxylate bismuth (3+) complex; D009942:Organometallic Compounds; D010880:Piperidines; D014233:Tricarboxylic Acids; D000431:Ethanol; D006632:Histamine; C053742:roxatidine acetate