From the Pharmacology Dept., Shahrekord University of Medical Sciences, Shahrekord, I.R. Iran.
Abstract: (4238 Views)
Antidepressant agents inhibit the neuronal reuptake of monoamines such as
serotonin (5-HT), noradrenaline (NA), and dopamine (DA). Several clinical and
animal studies have advocated the use of these agents in the management of pain.
In this study, therefore, the possibility of a correlation between the analgesic
activity of six serotonin specific reuptake inhibitor (SSRI) antidepressants and
their reported relative inhibitory potencies on monoamine reuptake was studied.
The antidepressants studied were citalopram, fluoxetine, fluvoxamine, sertraline,
and zimelidine.
Male ICI-WSP mice were given a 30 min pretreatment with antidepressants,
subcutaneously before challenge with 1 % intraperitoneal acetic acid. Abdominal
constrictions were evaluated over 20 min and percentage inhibition compared to
vehicle controls was calculated as a measure of analgesia. All the antidepressants
yielded linear log dose-analgesic response relationships from which ED50 values
were converted into relative potencies against fluoxetine as unity. Spearman's rank
correlations between relative potencies for analgesia and inhibition of monoamine
reuptake were examined. It was found that the correlation coefficients between
analgesia and 5HT, NA and DA reuptake were -0.54, -0.54 and -0.43,respectively,
suggesting that there was no overall rank correlation between these parameters.
This is somewhat surprising since monoamines are involved in the expression of
analgesia and their reuptake is considered to be a major component of the
pharmacology of these compounds. It is probable, however, that other differing
pharmacological properties such as opioid-like activity or diversity of
pharmacokinetic characteristics may disrupt any straightforward correlation
between monoamine reuptake and analgesia for the compounds examined.