Linked Life Data

18496672

Source:http://linkedlifedata.com/resource/pubmed/id/18496672

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-8-18
pubmed:abstractText
The pharmacological profiling of potent histamine H(3)-ligands initiated in a previous study is completed here. In vitro functional and binding studies revealed that several derivatives were selective H(3)-antagonists with nanomolar potency at human and guinea-pig histamine receptors, able to inhibit rat brain cholinesterase at micromolar concentrations and devoid of any cytotoxicity on cultured cells. Ex vivo binding experiments in rats showed that the most potent H(3)-antagonist, compound 5, had a prompt and long-lasting presence in the central nervous system (CNS), inhibiting [(3)H](R)-alpha-methylhistamine cortical binding [ED(50) (dose that elicits a 50% response) = 0.63 mg/kg intraperitoneally (i.p.)]. In the passive-avoidance test, compound 5, at 1.25 mg/kg i.p., was as effective as the anti-Alzheimer drug donepezil in attenuating scopolamine-induced amnesia in rats. These results suggest that a good CNS penetration and multitarget activity could account for the antiamnesic effect of this weak cholinesterase inhibitor and potent H(3)-antagonist (compound 5). This result represents a potential benchmark for the development of non-imidazole H(3)-antagonists/cholinesterase inhibitors with therapeutic potential in cognitive disorders.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0028-1298
pubmed:author
pubmed:issnType
Print
pubmed:volume
378
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
335-43
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
In vitro and in vivo pharmacological analysis of imidazole-free histamine H3 receptor antagonists: promising results for a brain-penetrating H3 blocker with weak anticholinesterase activity.
pubmed:affiliation
Dipartimento di Scienze Farmacologiche, Biologiche e Chimiche Applicate, Università di Parma, Parma, Italy.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't