ANTINOCICEPTIVE A CTIVITY OF ANTIDEPRESSANTS AND CORRELATI ON WITH NEUROTRANSMITIER INHIBITORY POTENCY

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.