UPTAKE AND RELEASE OF 5-HYDROXYTRYPTAMINE BY ENTERIC 5-HYDROXYTRYPTAMINERGIC NEURONS - EFFECTS OF FLUOXETINE (LILLY 110140) AND CHLORIMIPRAMINE

The effect of fluoxetine on uptake of 5‐hydroxytrypt‐amine(5‐HT) by enteric 5‐hydroxytryptaminergic neurones has been analyzed in order to compare further these neurones with 5‐HT neurones of the CNS. In addition, the effects of fluoxetine and chlorimipramine on efflux of [3H]‐5‐HT from the myenteric plexus were also evaluated. Fluoxetine was found to be a competitive inhibitor of 5‐HT uptake by the myenteric plexus and was a more potent inhibitor of 5‐HT uptake than was chlorimipramine. However, chlorimipramine enhanced the efflux of [3H]‐5‐HT more than could be explained by inhibition of 5‐HT uptake and, therefore. appears to have the additional action of releasing the amine. These observations, similar to those of others studying central neurones, support the view that enteric 5‐HT neurones resemble those of the CNS and are a useful model for the evaluation of drugs. 1979 British Pharmacological Society