Radioligand binding and photoaffinity labelling studies show a direct interaction of phenothiazines at 5-HT3 receptors.

The effects of a range of phenothiazines were examined on 5-hydroxytryptamine3 (5-HT3) receptors in membranes from NIE-115 neuroblastoma cells using radioligand binding. Chlorpromazine, fluphenazine, perphenazine, trifluoperazine and prochlorperazine inhibited specific binding of both the 5-HT3 receptor antagonist [3H]GR65630 and agonist [3H]meta-chlorophenylbiguanide (mCPBG), with Ki values ranging from 0.4 to 3.9 microM. The mode of action of chlorpromazine was further examined using photoaffinity labelling in the presence and absence of 5-HT. Saturation radioligand binding data with both [3H]GR65630 and [3H]mCPBG showed that photoaffinity labelling with chlorpromazine (1 microM) caused a decrease in the maximum number of binding sites observed (35% and 28% for agonist and antagonist, respectively). This decrease was not observed when the membranes were incubated in the presence of 5-HT. The results demonstrate a direct interaction of a range of phenothiazines at the 5-HT3 receptor binding site.