Tricyclic antidepressants
as long-acting local anesthetics

by
Sudoh Y, Cahoon EE, Gerner P, Wang GK.
Department of Anesthesia,
Harvard Medical School and
Brigham and Women's Hospital,
75 Francis St. 02115, Boston, MA, USA
Pain 2003 May;103(1-2):49-55


ABSTRACT

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.
Options
Doxepin
Imipramine
Maprotiline
Dumb drugs
Nortriptyline
Desipramine
Protriptyline
TCAs v SSRIs
Amitriptyline
Trimipramine
Antidepressants
TCA mechanisms
Residual depression
Retarded depression
Dothiepin v fluoxetine
Antidepressant toxicity
Imipramine v fluoxetine
Selectivity or multiplicity?
The monoamine hypothesis
Anaesthesia and anaesthetics
Antidepressants for pain-relief


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