Compound action potential inhibition produced by various antidepressants in the frog sciatic nerve.

Abstract:

:Although an inhibition of action potential conduction in nerve fibers possibly contributes to at least a part of antinociception produced by analgesics and the adjuvants, it has not been fully examined yet how the conduction inhibition differs in extent among their drugs. We investigated the effects of various antidepressants used as analgesic adjuvants on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. The results were compared with those of the other adjuvants that were reported previously. Antidepressants, duloxetine (serotonin and noradrenaline reuptake inhibitor, SNRI), fluoxetine (selective serotonin reuptake inhibitor, SSRI), amitriptyline (tricyclic tertiary amine), desipramine (tricyclic secondary amine) and maprotiline (tetracyclic secondary amine), reduced the peak amplitude of the CAP with half-maximal inhibitory concentration (IC50) values of 0.23, 1.5, 0.26, 1.6 and 0.95mM, respectively. Trazodone (non-SNRI, -SSRI, -tricyclic and -tetracyclic antidepressant) at 1.0mM reduced CAP amplitude by about 50%. The duloxetine and amitriptyline values were comparable to those of lamotrigine and carbamazepine (antiepileptics), dexmedetomidine (α2-adrenoceptor agonist) and ropivacaine, levobupivacaine and pramoxine (local anesthetics). The fluoxetine, desipramine, maprotiline and trazodone values were similar to those of oxymetazoline (α2-adrenoceptor agonist) and lidocaine, cocaine, procaine and prilocaine (local anesthetics). The antidepressants' IC50 values were much larger than that of tetracaine (local anesthetic). In conclusion, the six antidepressants inhibited CAPs with efficacies comparable to some antiepileptics, α2-adrenoceptor agonists and local anesthetics. It was suggested that antidepressants inhibit nerve conduction with efficacies comparable to those of the other adjuvants.

journal_name

Eur J Pharmacol

authors

Hirao R,Fujita T,Sakai A,Kumamoto E

doi

10.1016/j.ejphar.2017.11.047

subject

Has Abstract

pub_date

2018-01-15 00:00:00

pages

122-128

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(17)30782-3

journal_volume

819

pub_type

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