Linked Life Data

12749958

Source:http://linkedlifedata.com/resource/pubmed/id/12749958

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2003-5-16
pubmed:abstractText
Amitriptyline, nortriptyline, imipramine, doxepin, desipramine, protriptyline, trimipramine, and maprotiline are tricyclic antidepressants (TCAs) used orally in treating major depressive disorders. Recent studies showed that amitriptyline is more potent in blocking the sciatic nerve functions in vivo by local injection than bupivacaine, a long-acting local anesthetic. We therefore tested whether various TCAs could likewise act as local anesthetics in vivo after single injection via the rat sciatic notch. The duration of complete sciatic nerve blockade by TCAs and the time to reach full recovery were measured with neurobehavioral assays and compared with results from bupivacaine. Amitriptyline, doxepin, and imipramine at 5mM elicited a longer complete sciatic nerve blockade than did bupivacaine at 15.4mM (0.5%), whereas trimipramine and desipramine at 5mM produced a shorter blockade. In contrast, nortriptyline, protriptyline, and maprotiline failed to elicit complete sciatic nerve blockade. Thus, TCAs have very different efficacy as local anesthetics in vivo. The duration of rat sciatic nerve blockade in vivo by TCAs is not well correlated with the 50% inhibitory concentration (IC(50)) of TCAs in blocking human cardiac Nav1.5 Na(+) channels expressed in human embryonic kidney cells. With this in vitro expression system, TCAs appear more potent than bupivacaine as Na(+) channel blockers in Nav1.5 Na(+) channels. We suggest that the ability of TCAs to pass through various membrane barriers within peripheral nerve trunks is crucial to their local anesthetic efficacy in vivo. TCAs with a tertiary amine appear more effective in penetrating these membrane barriers than TCAs with a secondary amine.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0304-3959
pubmed:author
pubmed:issnType
Print
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
49-55
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:12749958-Amines, pubmed-meshheading:12749958-Anesthetics, Local, pubmed-meshheading:12749958-Animals, pubmed-meshheading:12749958-Antidepressive Agents, Tricyclic, pubmed-meshheading:12749958-Cell Line, pubmed-meshheading:12749958-Dose-Response Relationship, Drug, pubmed-meshheading:12749958-Doxepin, pubmed-meshheading:12749958-Electric Impedance, pubmed-meshheading:12749958-Embryo, Mammalian, pubmed-meshheading:12749958-Humans, pubmed-meshheading:12749958-Kidney, pubmed-meshheading:12749958-Male, pubmed-meshheading:12749958-Membrane Potentials, pubmed-meshheading:12749958-Motor Activity, pubmed-meshheading:12749958-Neurologic Examination, pubmed-meshheading:12749958-Nortriptyline, pubmed-meshheading:12749958-Pain, pubmed-meshheading:12749958-Pain Measurement, pubmed-meshheading:12749958-Patch-Clamp Techniques, pubmed-meshheading:12749958-Proprioception, pubmed-meshheading:12749958-Rats, pubmed-meshheading:12749958-Rats, Sprague-Dawley, pubmed-meshheading:12749958-Recovery of Function, pubmed-meshheading:12749958-Sciatic Nerve, pubmed-meshheading:12749958-Substance-Related Disorders, pubmed-meshheading:12749958-Time Factors, pubmed-meshheading:12749958-Transfection
pubmed:year
2003
pubmed:articleTitle
Tricyclic antidepressants as long-acting local anesthetics.
pubmed:affiliation
Department of Anesthesia, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115 USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.