ISSN:
1573-904X
Keywords:
histamine-H2-antagonists
;
acetylcholinesterase
;
acetylcholine—brain levels
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Famotidine and selected H2-antagonists were evaluated with respect to toxicity and selected pharmacological activities. When administered intraperitoneally to mice at a dose equivalent to 10 times their respective H2-antagonist ED50 values, no deaths were observed. Similarly, no alteration in brain ACh concentrations or overt pharmacological effects were noted. However, at 400 mg/kg, ranitidine produced 89% lethality, followed by cimetidine (11%) and famotidine. Only cimetidine and famotidine at this dose significantly elevated brain acetylcholine levels. These results do not correlate with the in vitro data, where ORF-17578 and ranitidine were the most potent entities with respect to acetylcholinesterase inhibition (∼1–2 × 10−6 M), followed by nizatidine 〉 cimetidine 〉 famotidine. The sulfoxide metabolites of ranitidine and cimetidine were approximately one-tenth as potent as their parent compounds with respect to inhibition of acetylcholinesterase. Direct muscarinic stimulation or potentiation of acetylcholine-induced contraction in ileal tissue was not observed for any of the H2-antagonists.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1015994607652
Permalink
