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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
1997-3-17
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pubmed:abstractText |
Cetiedil ((+/-)-2-cyclohexyl-2-(3-thienyl)ethanoic acid 2-(hexahydro-1 H-azepin-1-yl) ethyl ester) possesses anti-sickling and analgesic, antispasmodic, local anaesthetic and vasodilator activities. A total synthesis and circular dichroism spectra of the enantiomers of cetiedil is described, together with a comparison of their effectiveness as blockers of the Ca(2+)-activated K+ permeability of rabbit erythrocytes; the contractile response of intestinal smooth muscle to acetylcholine; the Ca(2+)-dependent contraction of depolarized intestinal muscle; and the cell volume-sensitive K+ permeability (Kvol) of liver cells. The enantiomers did not differ substantially in their ability to block the Ca(2+)-activated K+ permeability of rabbit red cells or in their effectiveness as blockers of the contractile response of depolarized smooth muscle to externally applied Ca2+. There was a clear difference in the muscarinic blocking activity of the enantiomers, as assessed by inhibition of the contractile response of intestinal smooth muscle to acetylcholine; (+)-cetiedil was 7.7 +/- 0.2 (s.d.) times more active than the (-) from. The enantiomers also differed in their potency as blockers of the increase in membrane conductance which occurs when liver cells swell. The concentration of (+)-cetiedil needed to reduce the conductance increase by 50% was 2.04 +/- 0.54 (s.d.) microM; (-)-cetiedil was 2.6 +/- 0.8 (s.d.) times less active (IC50 of 5.2 +/- 1.2 microM). Differences in the biological actions of the enantiomers of cetiedil indicate that a more extensive study could be rewarding in relation to the use of the enantiomers both in therapeutics and in the study of K+ channels.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-3573
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
48
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
851-7
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pubmed:dateRevised |
2009-9-29
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pubmed:meshHeading |
pubmed-meshheading:8887737-Animals,
pubmed-meshheading:8887737-Antisickling Agents,
pubmed-meshheading:8887737-Azepines,
pubmed-meshheading:8887737-Dose-Response Relationship, Drug,
pubmed-meshheading:8887737-Erythrocytes,
pubmed-meshheading:8887737-Muscle, Smooth,
pubmed-meshheading:8887737-Muscle Contraction,
pubmed-meshheading:8887737-Potassium Channel Blockers,
pubmed-meshheading:8887737-Rabbits,
pubmed-meshheading:8887737-Rats,
pubmed-meshheading:8887737-Stereoisomerism
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pubmed:year |
1996
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pubmed:articleTitle |
The synthesis and some pharmacological actions of the enantiomers of the K(+)-channel blocker cetiedil.
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pubmed:affiliation |
Department of Chemistry, University College London, UK.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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