Mepacrine-induced inhibition of the inward current mediated by 5-HT3 receptors in rat nodose ganglion neurones.

1. With the whole-cell patch clamp technique, the effect of the antimalarial drug, mepacrine (quinacrine) on the inward current mediated by 5-HT3 receptors (5-hydroxytryptamine (5-HT)-induced current) was investigated in isolated nodose ganglion neurones of the rat. 2. 5-HT and the selective 5-HT3 receptor agonists, 2-methyl-5-HT and m-chlorophenylbiguanide elicited an inward current which reversed at around 0 mV and quickly desensitized to a steady state level. 3. Mepacrine dose-dependently inhibited the peak current induced by 5-HT with an IC50 of 2.1 microM and an apparent Hill coefficient of 0.99. 4. Mepacrine increased the decay rate of the 5-HT-induced current. 5. The effect of mepacrine on the 5-HT-induced current was reversible and not dependent on membrane potential. The reversal potential of the 5-HT-induced current was not affected. 6. Intracellular mepacrine had no significant effect on the 5-HT-induced current and did not block the extracellular action of mepacrine. 7. Concentration-response curves in the presence and absence of mepacrine suggest a non-competitive inhibition of 5-HT-induced current by mepacrine.